bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Pleistocene refugia for Arctic White Heather (Cassiope tetragona) supported by population genomics analyses of contemporary and Little-Ice-Age samples
Authors: Elphinstone Cassandra , Hernandez Fernando , Todesco Marco , Légaré Jean-Sébastien , Cheung Winnie , Sokoloff Paul C. , Hofgaard Annika , Christiansen Casper T. , Frei Esther R. , Lévesque Esther , Daskalova Gergana N. , Thomas Haydn J. D. , Myers-Smith Isla H. , Harris Jacob A. , Saarela Jeffery M. , May Jeremy L. , Obst Joachim , Boike Julia , Clark Karin , MacIntosh Katie , Betway-May Katlyn R. , Björkman Mats P. , Moody Michael L. , Schmidt Niels Martin , Molgaard Per , Björk Robert G. , Hollister Robert D. , Bull Roger D. , Agger Sofie , Maire Vincent , Case Liam , Henry Greg H.R. , Rieseberg Loren H. 
Published: July 2023

AbstractAimArctic plants survived the Pleistocene glaciations in unglaciated refugia, but the number of these refugia is often unclear. We use high-resolution genomic data from present-day and Little-Ice-Age populations of Arctic White Heather (Cassiope tetragona) to re-evaluate the biogeography of this species and determine whether it had multiple independent refugia or a single refugium in Beringia.LocationCircumpolar Arctic and Coastal British Columbia (BC) alpineTaxonCassiope tetragonaL., subspeciessaximontanaandtetragona,outgroupC. mertensiana(Ericaceae)MethodsWe built genotyping-by-sequencing (GBS) libraries usingCassiope tetragonatissue from 36 Arctic locations, including two ∼250-500-year-old populations collected under glacial ice on Ellesmere Island, Canada. We assembled ade novoGBS reference and called variants in dDocent. Population structure, genetic diversity, and demography were inferred from PCA, ADMIXTURE, fastsimcoal2, SplitsTree, and several population genomics statistics.ResultsPopulation structure analyses identified 4-5 clusters that align with geographic locations. Nucleotide diversity was highest in Beringia and decreased eastwards across Canada. Demographic coalescent analysis of the site-frequency-spectrum dated the following splits from Alaska: BC subspeciessaximontana(6 mya), Russia (1.5 mya), Europe (>300-600 kya), Greenland (100 kya). Northern Canada populations appear to be from the current interglacial (7-9 kya). Genetic variants from Alaska appeared more frequently in present-day than historic plants on Ellesmere Island.ConclusionsDemographic analyses show BC, Alaska, Russia, Europe, and Greenland all had separate refugia during the last major glaciations. Northern Canadian populations appear to be founded during the current interglacial with genetic contributions from Alaska, Europe, and Greenland. On Ellesmere Island, there is evidence for continued, recent gene flow with foreign variants introduced in the last 250-500 years. These results suggest that a re-analysis of other Arctic species with shallow population structure using higher resolution genomic markers and demographic analyses may help reveal deeper structure and other circumpolar glacial refugia.
Mapping general anesthesia states based on electro-encephalogram transition phases
Authors: Loison V. , Voskobiynyk Y. , Lindquist B. , Necula D. , Longrois D. , Paz J. , Holcman D. 
Published: July 2023

AbstractCortical electro-encephalography (EEG) has become the clinical reference for monitoring unconsciousness during general anesthesia. The current EEG-based monitors classify general anesthesia states simply as underdosed, adequate, or overdosed, with no transition phases among these states, and therefore no predictive power. To address the issue of transition phases, we analyzed EEG signal of isoflurane-induced general anesthesia in mice. We adopted a data-driven approach and utilized signal processing to trackθ- andδ- band dynamics as well as iso-electric suppressions. By combining this approach with machine learning, we developed a fully-automated algorithm. We found that the dampening of theδ-band occurred several minutes before significant iso-electric suppression episodes. Additionally, we observed a distinctγ-frequency oscillation that persisted for several minutes during the recovery phase following isoflurane-induced overdose. Finally, we constructed a map summarizing multiple states and their transitions which can be utilized to predict and prevent overdose during general anesthesia. The transition phases we identified and algorithm we developed may allow clinicians to prevent inadequate anesthesia, and thus individually tailor anesthetic regimens.1Significance statementIn human patients, overdosing during general anesthesia can lead to cognitive impairment. Cortical electro-encephalograms are used to measure the depth of anesthesia. They allow for correction, but not prevention, of overdose. However, data-driven approaches open new possibilities to predict the depth of anesthesia. We established an electro-encephalogram signalprocessing pipeline, and constructed a predictive map representing an ensemble of gradual sedation states during general anesthesia in mice. In particular, we identified key electroencephalogram patterns which anticipate signs of overdose several minutes before they occur. Our results bring a novel paradigm to the medical community, allowing for the development of individually tailored and predictive anesthetic regimens.
Social influence in adolescence: behavioral and neural responses to peer and expert opinion
Authors: Irani Fatemeh , Muotka Joona , Lyyra Pessi , Parviainen Tiina , Monto Simo 
Published: July 2023

ABSTRACTSocial influence plays a crucial role during the teen years, with adolescents supposedly exhibiting heightened sensitivity to their peers. In this study, we examine how social influence from different sources, particularly those with varying normative and informational significance, affect adolescents’ opinion change. Furthermore, we investigate underlying neural dynamics to determine whether these two behaviorally similar influences share their neural mechanisms. Twenty-three participants (14-17 years old) gave their opinions about facial stimuli and received feedback from either a peer group or an expert group, while brain responses were recorded using concurrent magnetoencephalography. In a second rating session, we found that participants’ opinions changed in line with conflicting feedback, but only when the feedback was lower than their initial evaluation. On the neural level, conflict with the peer group evoked stronger neural responses than conflict with experts in the 230-400 ms time window. Nevertheless, there was no greater conformity toward peers. Moreover, conflict compared to no conflict decreased neural oscillations in the beta frequency range (20–27 Hz) at the right frontal and parietal channels. Taken together, our findings do not support the general assumption that adolescent behavior is excessively vulnerable to peer norms, although we found heightened neural sensitivity to peer feedback.
A novel tamanavirus (Flaviviridae) of the European common frog (Rana temporaria) encodes a divergent class 1b XRN1-resistant RNA element
Authors: Parry Rhys , Slonchak Andrii , Campbell Lewis J. , Newton Natalee D. , Debat Humberto J. , Gifford Robert J. , Khromykh Alexander A 
Published: July 2023

AbstractFlavivirids are small, enveloped, positive-sense RNA viruses from theFlaviviridaefamily with genomes between ∼9-13kb. Metatranscriptomic analyses of metazoan organisms have revealed a diversity of flavivirus-like or flavivirid viral sequences in fish and marine invertebrate groups. To date, however, no flavivirus-like or flavivirid has been identified in amphibians. To remedy this, we investigated the virome of the European common frog (Rana temporaria) in the United Kingdom, utilising high-throughput sequencing at six catch locations. De novo assembly revealed a coding-complete virus contig of a novel flavivirid ∼11.2kb in length. The virus encodes a single open reading frame of 3456 amino acids and 5’ and 3’ untranslated regions (UTRs) of 227 and 666nt, respectively. We named this virus Rana tamanavirus (RaTV), as BLASTp analysis of the polyprotein showed the closest relationships to Tamana bat virus (TABV) and Cyclopterus lumpus virus fromPteronotus parnelliiandCyclopterus lumpus, respectively. Phylogenetic analysis of the RaTV polyprotein compared toFlavivirusand Flavivirus-like members indicated that RaTV was sufficiently divergent and basal to the vertebrate Tamanavirus clade. In addition to the Mitcham strain, partial but divergent RaTV, 95.64-97.39% pairwise nucleotide identity, were also obtained from the Poole and Deal samples, indicating that RaTV is widespread in UK frog samples. Bioinformatic analyses of putative secondary structures in the 3′-UTR of RaTV indicated a potential exoribonuclease-resistant RNA (xrRNA) structure identified in flaviviruses and TABV. To examine this biochemically, we conducted an in vitro XRN1 digestion assay showing that RaTV likely forms a divergent but functionally homologous XRN1-resistant xrRNA.
Epigenetic and neural correlates of selective social attention across adulthood
Authors: Puglia Meghan H. , Lynch Morgan E. , Nance Madelyn G. , Connelly Jessica J. , Morris James P. 
Published: July 2023

AbstractSocial isolation is one of the strongest predictors of increased risk of mortality in older adulthood. The ability to form and maintain the social relationships that mitigate this risk is partially regulated by the oxytocinergic system and one’s ability to attend to and process social information. We have previously shown that an epigenetic change to the DNA of the oxytocin receptor gene (OXTRmethylation) affects the salience of social information in young adults. Little is known about how the oxytocinergic system ages and what effect this aging system has on social cognitive abilities throughout the lifespan. Here we explore age-related differences in the association between neural response during selective social attention andOXTRDNA methylation in young and older adults. We find that older adults activate diffuse areas of visual cortex and dorsolateral prefrontal cortex during selective social attention, consistent with the dedifferentiation and compensatory neural activation commonly reported in aging. We find a significant age-by-OXTRmethylation interaction on neural response when attending to social stimuli in a complex display; young adults display a positive association betweenOXTRmethylation and neural activation, replicating our prior finding that young adults with presumed diminished endogenous access to oxytocin recruit regions of the attentional cortex to a greater extent. This association does not hold for older adults. Instead, perceived social support interacts withOXTRmethylation to influence neural response during selective social attention. These data suggest that environmental factors like social support moderate biological processes in aging and highlight the importance of a lifespan perspective for understanding associations between individual differences in the oxytocinergic system, neural function, and social behavior.
Cellular traits regulate fluorescence-based bio-optical phenotypes of coral photosymbionts livingin-hospite
Authors: McQuagge Audrey , Pahl K. Blue , Wong Sophie , Melman Todd , Linn Laura , Lowry Sean , Hoadley Kenneth D. 
Published: July 2023

AbstractDiversity across algal familySymbiodiniaceaecontributes to the environmental resilience of certain coral species. Chlorophyll-afluorescence measurements are frequently used to determine symbiont health and resilience, but more work is needed to refine these tools and establish how they relate to underlying cellular traits. We examined trait diversity in symbionts from the generasCladocopiumandDurusdinium,collected from 12 aquacultured coral species. Photophysiological metrics (ΦPSII, σPSII, ρ, τ1, τ2, ABQ, NPQ, and qP) were assessed using a prototype multi-spectral fluorometer over a variable light protocol which yielded a total of 1360 individual metrics. Photophysiological metrics were then used to establish four unique phenotypic variants. Corals harboring C15 were predominantly found within a single phenotype which clustered separately from all other coral fragments. The majority ofDurusdiniumdominated colonies also formed a separate phenotype which it shared with a few C1 dominated corals. C15 and D1 symbionts appear to differ in which mechanisms they employ to dissipate excess light energy. Spectrally dependent variability is also observed across phenotypes that may relate to differences in photopigment utilization. Cell physiology (atomic C:N:P, cell size, chlorophyll-a, neutral lipid content) was also assessed within each sample and differ across phenotypes, linking photophysiological metrics with underlying primary cellular traits. Strong correlations between first– and second-order traits, such as Quantum Yield and cellular N:P content, or light dissipation pathways (qP and NPQ) and C:P underline differences across symbiont types and may also provide a means for using fluorescence-based metrics as biomarkers for certain primary-cellular traits.
Myeloid cell activation during Zika virus encephalitis predicts recovery of functional cortical connectivity
Authors: Agner Shannon C. , Brier Lindsey M. , Hill Jeremy , Liu Ethan , Bice Annie , Rahn Rachel M. , Culver Joseph P. , Klein Robyn S. 
Published: July 2023

AbstractNeurologic complications of Zika virus (ZIKV) infection across the lifespan have been described during outbreaks in Southeast Asia, South America, and Central America since 2016. In the adult CNS ZIKV tropism for neurons is tightly linked to its effects, with neuronal loss within the hippocampus during acute infection and protracted synapse loss during recovery, which is associated with cognitive deficits. The effects of ZIKV on cortical networks have not been evaluated. Although animal behavior assays have been used previously to model cognitive impairment, in vivo brain imaging can provide orthogonal information regarding the health of brain networks in real time, providing a tool to translate findings in animal models to humans. In this study, we use widefield optical imaging to measure cortical functional connectivity (FC) in mice during acute infection with, and recovery from, intracranial infection with a mouse-adapted strain of ZIKV. Acute ZIKV infection leads to high levels of myeloid cell activation, with loss of neurons and presynaptic termini in the cerebral cortex and associated loss of FC primarily within the somatosensory cortex. During recovery, neuron numbers, synapses and FC recover to levels near those of healthy mice. However, hippocampal injury and impaired spatial cognition persist. The magnitude of activated myeloid cells during acute infection predicted both recovery of synapses and the degree of FC recovery after recovery from ZIKV infection. These findings suggest that a robust inflammatory response may contribute to the health of functional brain networks after recovery from infection.Significance StatementDetermining the long-term cognitive impact of infections is clinically challenging. We found that the degree of myeloid cell activation correlated with the degree of recovery of functional connectivity after recovery from ZIKV encephalitis. Using functional cortical connectivity, we demonstrate that interhemispheric cortical connectivity is decreased in individuals with acute ZIKV encephalitis. This correlates with decreased presynaptic terminals in the somatosensory cortex. During recovery from ZIKV infection, presynaptic terminals recover, which is associated with recovered interhemispheric connectivity. This suggests a role for activated myeloid cells in maintenance of cognition and further supports the contribution of synapses in the cortex to functional networks in the brain, which can be detected by widefield optical imaging. These findings also suggest neuroinflammation may play a neuroprotective role in addition to aiding in local virologic control.
This microtubule does not exist: Super-resolution microscopy image generation by a diffusion model
Authors: Saguy Alon , Nahimov Tav , Lehrman Maia , Gómez-de-Mariscal Estibaliz , Hidalgo-Cenalmor Iván , Alalouf Onit , Henriques Ricardo , Shechtman Yoav 
Published: July 2023

AbstractGenerative models, such as diffusion models, have made significant advancements in recent years, enabling the synthesis of high-quality realistic data across various domains. Here, we explore the adaptation and training of a diffusion model on super-resolution microscopy images from publicly available databases. We show that the generated images resemble experimental images, and that the generation process does not memorize existing images from the training set. Additionally, we compare the performance of a deep learning-based deconvolution method trained using our generated high-resolution data versus training using high-resolution data acquired by mathematical modeling of the sample. We obtain superior reconstruction quality in terms of spatial resolution using a small real training dataset, showing the potential of accurate virtual image generation to overcome the limitations of collecting and annotating image data for training. Finally, we make our pipeline publicly available, runnable online, and user-friendly to enable researchers to generate their own synthetic microscopy data. This work demonstrates the potential contribution of generative diffusion models for microscopy tasks and paves the way for their future application in this field.
A Novel Drosophila Model to Investigate Adipose Tissue Macrophage Infiltration (ATM) and Obesity highlights the Therapeutic Potential of Attenuating Eiger/TNFα Signaling to Ameliorate Insulin Resistance and ATM
Authors: Mirzoyan Zhasmine , Valenza Alice , Zola Sheri , Bonfanti Carola , Arnaboldi Lorenzo , Ferrari Nicholas , Pollard John , Lupi Valeria , Cassinelli Matteo , Frattaroli Matteo , Sahin Mehtap , Pasini Maria Enrica , Bellosta Paola 
Published: July 2023

AbstractObesity is a global health concern associated with various metabolic disorders including insulin resistance and adipose tissue inflammation characterized by adipose tissue macrophage (ATM) infiltration. In this study, we present a novelDrosophilamodel to investigate the mechanisms underlying ATM infiltration and its association with obesity-related pathologies. Furthermore, we demonstrate the therapeutic potential of attenuating Eiger/TNFα signaling to ameliorate insulin resistance and ATM. To study ATM infiltration and its consequences, we established a novelDrosophilamodel (OBL) that mimics key aspects of human adipose tissue and allows for investigating ATM infiltration and other related metabolic disorders in a controlled experimental system. We employed genetic manipulation to reduce ecdysone levels to prolong the larval stage. These animals are hyperphagic, and exhibit features resembling obesity in mammals, including increased lipid storage, adipocyte hypertrophy, and high levels of circulating glucose. Moreover, we observed a significant infiltration of immune cells (hemocytes) in the fat bodies accompanied by insulin resistance and systemic metabolic dysregulation. Furthermore, we found that attenuation of Eiger/TNFα signaling and using metformin and anti-oxidant bio-products like anthocyanins led to a reduction in ATM infiltration and improved insulin sensitivity.Our data suggest that the key mechanisms that trigger immune cell infiltration into adipose tissue are evolutionarily conserved and may provide the opportunity to developDrosophilamodels to better understand pathways critical for immune cell recruitment into adipose tissue, in relation to the development of insulin resistance in metabolic diseases such as obesity and type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). We believe that our OBL model can also be a valuable tool and provide a platform either to perform genetic screens or to test the efficacy and safety of novel therapeutic interventions for these diseases.
Exogenous butyrate inhibits butyrogenic metabolism and alters expression of virulence genes inClostridioides difficile
Authors: Pensinger Daniel A. , Dobrila Horia A. , Stevenson David M. , Davis Nicole M. , Amador-Noguez Daniel , Hryckowian Andrew J. 
Published: July 2023

ABSTRACTThe gut microbiome engenders colonization resistance against the diarrheal pathogenClostridioides difficilebut the molecular basis of this colonization resistance is incompletely understood. A prominent class of gut microbiome-produced metabolites important for colonization resistance againstC. difficileis short chain fatty acids (SCFAs). In particular, one SCFA (butyrate) decreases the fitness ofC. difficilein vitro and is correlated withC. difficile- inhospitable gut environments, both in mice and in humans. Here, we demonstrate that butyrate-dependent growth inhibition inC. difficileoccurs under conditions whereC. difficilealso produces butyrate as a metabolic end product. Furthermore, we show that exogenous butyrate is internalized intoC. difficilecells, is incorporated into intracellular CoA pools where it is metabolized in a reverse (energetically unfavorable) direction to crotonyl-CoA and (S)-3-hydroxybutyryl-CoA and/or 4-hydroxybutyryl-CoA. This internalization of butyrate and reverse metabolic flow of butyrogenic pathway(s) inC. difficilecoincides with alterations in toxin production and sporulation. Together, this work highlights butyrate as a signal of aC. difficileinhospitable environment to whichC. difficileresponds by producing its diarrheagenic toxins and producing environmentally-resistant spores necessary for transmission between hosts. These findings provide foundational data for understanding the molecular and genetic basis of howC. difficilegrowth is inhibited by butyrate and how butyrate serves as a signal to alterC. difficilevirulence in the face of a highly competitive and dynamic gut environment.IMPORTANCEThe gut microbiome engenders colonization resistance against the diarrheal pathogenClostridioides difficilebut the molecular basis of this colonization resistance is incompletely understood, which hinders the development of novel therapeutic interventions forC. difficileinfection (CDI). We investigated howC. difficileresponds to butyrate, an end-product of gut microbiome community metabolism which inhibitsC. difficilegrowth. We show that exogenously-produced butyrate is internalized intoC. difficile, which inhibitsC. difficilegrowth by interfering with its own butyrate production. This growth inhibition coincides with the expression of virulence-related genes. Future work to disentangle the molecular mechanisms underlying these growth and virulence phenotypes will likely lead to new strategies to restrictC. difficilegrowth in the gut and minimize its pathogenesis during CDI.