bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning and embodied decisions in active inference
Authors: Priorelli Matteo , Stoianov Ivilin Peev , Pezzulo Giovanni 
Published: August 2024

AbstractBiological organisms constantly face the necessity to act timely in dynamic environments and balance choice accuracy against the risk of missing valid opportunities. As formalized by embodied decision models, this might require brain architectures wherein decision-making and motor control interact reciprocally, in stark contrast to traditional models that view them as serial processes. Previous studies have assessed that embodied decision dynamics emerge naturally under active inference – a computational paradigm that considers action and perception as subject to the same imperative of free energy minimization. In particular, agents can infer their targets by using their own movements (and not only external sensations) as evidence, i.e., viaself-evidencing. Such models have shown that under appropriate conditions, action-generated feedback can stabilize and improve decision processes. However, how adaptation of internal models to environmental contingencies influences embodied decisions is yet to be addressed. To shed light on this challenge, in this study we systematically investigate the learning dynamics of an embodied model of decision-making during atwo-alternative forced choicetask, using a hybrid (discrete and continuous) active inference framework. Our results show that active inference agents can adapt to embodied contexts by learning various statistical regularities of the task – namely, prior preferences for the correct target, cue validity, and response strategies that prioritize faster or slower (but more accurate) decisions. Crucially, these results illustrate the efficacy of learning discrete preferences and strategies using sensorimotor feedback from continuous dynamics.
Three Open Questions in Polygenic Score Portability
Authors: Wang Joyce Y. , Lin Neeka , Zietz Michael , Mares Jason , Narasimhan Vagheesh M. , Rathouz Paul J. , Harpak Arbel 
Published: August 2024

AbstractA major obstacle hindering the broad adoption of polygenic scores (PGS) is their lack of “portability” to people that differ—in genetic ancestry or other characteristics—from the GWAS samples in which genetic effects were estimated. Here, we use the UK Biobank to measure the change in PGS prediction accuracy as a continuous function of individuals’ genome-wide genetic dissimilarity to the GWAS sample (“genetic distance”). Our results highlight three gaps in our understanding of PGS portability. First, prediction accuracy is extremely noisy at the individual level and not well predicted by genetic distance. In fact, variance in prediction accuracy is explained comparably well by socioeconomic measures. Second, trends of portability vary across traits. For several immunity-related traits, prediction accuracy drops near zero quickly even at intermediate levels of genetic distance. This quick drop may reflect GWAS associations being more ancestry-specific in immunity-related traits than in other traits. Third, we show that even qualitative trends of portability can depend on the measure of prediction accuracy used. For instance, for white blood cell count, a measure of prediction accuracy at the individual level (reduction in mean squared error) increases with genetic distance. Together, our results show that portability cannot be understood through global ancestry groupings alone. There are other, understudied factors influencing portability, such as the specifics of the evolution of the trait and its genetic architecture, social context, and the construction of the polygenic score. Addressing these gaps can aid in the development and application of PGS and inform more equitable genomic research.
Broad bandwidth photoacoustic imaging using a PVDF receiver array
Authors: Chandramoorthi Sowmiya , López-Marín Antonio , Beurskens Robert , van der Steen Antonius F.W. , van Soest Gijs 
Published: August 2024

AbstractPhotoacoustic (PA) signals are typically broadband, with a correlation between their frequency characteristics and source dimension. The transducers that are commonly used for PA acquisition are optimized for pulse-echo ultrasound imaging and are primarily based on inorganic piezoelectrics in ceramic, single-crystal, or composite form. These transducers are band-limited which limits their functionality as receivers for broadband PA signals. Custom broadband transducers are expensive and complex to manufacture. In this work, we propose to use a poly vinylidene difluoride (PVDF) based transducer for PA acquisition in combination with a commercial single-crystal linear array for pulse-echo acquisition. An 8-element PVDF array with 20dB onboard amplification was built in-house. The PVDF receiver is transparent to the pulse-echo ultrasound, and both transducers were positioned such that they image the same volume. The combined PA raw data from the PVDF and the linear array demonstrated the feasibility of achieving a broader overall reception bandwidth. This study establishes a foundation for a simpler acquisition system that enhances PA signal quality, co-registered with conventional ultrasound imaging, which may support the clinical adoption of PA imaging.
Natural variation in physical responses to waterlogging across climate-diverse pennycress accessions
Authors: Combs-Giroir Rachel , Lagergren John , Jacobson Daniel A. , Gschwend Andrea R. 
Published: August 2024

AbstractFluctuations in flooding and differences in hydrological gradients affect the geographic distribution of plant species across ecosystems, resulting in the presence of adaptive traits in populations that confer enhanced fitness in flooded environments. Many winter annual crops, such as pennycress (Thlaspi arvenseL.), are subjected to heavy precipitation events during their growing season, which are increasing in frequency due to climate change. Therefore, it is essential to identify pennycress accessions with natural variation in flooding resilience. In this study, we used climate modeling data to assess spring soil moisture levels in the geographic origins of 471 natural pennycress accessions. We selected 34 accessions with variations in predicted soil moisture to test survivability under prolonged waterlogging at the rosette stage. This identified variation in waterlogging tolerance, where six accessions had 0% survivability and nine accessions had 100% survivability. It took at least seven weeks for the first accessions to die under waterlogging, indicating that pennycress is hardy to prolonged waterlogging at the vegetative stage. Furthermore, we chose three “susceptible” and five “tolerant” accessions to waterlog for one week at the reproductive stage, the growth stage aligned with heavy spring rainfall. Six accessions had significantly reduced seed weight at maturity after recovery from waterlogging, and two accessions had minimal impacts on growth and seed yield after waterlogging. These two accessions can be used in future studies to explore adaptive traits, such as changes in root characteristics, as well as the genetic variation that contributes to pennycress waterlogging tolerance.
An Enzyme-Linked Immunosorbent Assay (ELISA)-based Activity Assay for AMP-Activated Protein Kinase (AMPK)
Authors: Nguyen Trezze P , Liu Yang 
Published: August 2024

AbstractAMP-activated protein kinase (AMPK) is the master regulator of cellular and organismal energy homeostasis, playing an essential role in modulating metabolism as well as other cellular processes. Efforts have been made to discover pharmacological modulators of AMPK activity because of their therapeutic potentials against various diseases. Measuring AMPK activity in vitro is a fundamental step for testing AMPK activators and inhibitors. Here we report an enzyme-linked immunosorbent assay (ELISA)-based AMPK activity assay with simple steps and high sensitivity, which represents an alternative in-house method to the traditional radioactive method as well as other techniques that require special reagents and commercial reagent kits.
Urinary Sodium Wasting and Disrupted Collecting Duct Function in Mice with dRTA-CausingSLC4A1Mutations
Authors: Mungara Priyanka , MacNaughton Kristina , Ullah AKM Shahid , Essuman Grace , Chelangarimiyandoab Forough , Mumtaz Rizwan , Hennings J. Christopher , Hübner Christian A. , Eladari Dominique , Alexander R. Todd , Cordat Emmanuelle 
Published: August 2024

AbstractDistal renal tubular acidosis (dRTA) results in metabolic acidosis due to impaired urinary acidification and can also result in an unexplained urinary sodium-wasting phenotype. Here, we report the generation and characterization of a novel dRTA mutant mouse line, Ae1 L919X knockin (KI). Homozygous L919X KI mice exhibit typical dRTA features including a reduced ability to acidify urine in response to an acid load. This renal acidification defect was associated with a reduced number of Ae1-positive type A intercalated cells. To assess whether these mice exhibit urinary sodium-wasting as seen in some dRTA patients, homozygous KI L919X and the previously described R607H KI mice were fed a salt-depleted acid diet. In line with human patients, both mouse strains exhibited urinary sodium loss. Additionally, we identified increased expression of tight junction proteins claudin-4 and -10b, suggesting a compensatory paracellular pathway in the loop of Henle. Consistent with data from human patients, L919X KI mice displayed a milder phenotype than R607H KI mice. Our findings reveal that both mouse strains are appropriate models for dRTA with a urinary salt-wasting phenotype and a compensatory up-regulation of the paracellular pathway in the ascending limb of the loop of Henle.
CD4+but not CD8+T cells are required for protection against severe guinea pig cytomegalovirus infections
Authors: Rollman Tyler B. , Berkebile Zachary W. , Hicks Dustin M. , Hatfield Jason S. , Chauhan Priyanka , Pravetoni Marco , Schleiss Mark R. , Milligan Gregg N. , Morgan Terry K. , Bierle Craig J. 
Published: August 2024

AbstractHuman cytomegalovirus (HCMV) is a ubiquitous herpesvirus and the leading cause of infectious disease related birth defects worldwide. How the immune response modulates the risk of intrauterine transmission of HCMV after maternal infection remains poorly understood. Maternal T cells likely play a critical role in preventing infection at the maternal-fetal interface and limiting spread across the placenta, but concerns exist that immune responses to infection may also cause placental dysfunction and adverse pregnancy outcomes. This study investigated the role of CD4+and CD8+T cells in a guinea pig model of primary cytomegalovirus infection. Monoclonal antibodies specific to guinea pig CD4 and CD8 were used to deplete T cells in non- pregnant and in pregnant guinea pigs after mid-gestation. CD4+T cell depletion increased the severity of illness, caused significantly elevated viral loads, and increased the rate of congenital guinea pig cytomegalovirus (GPCMV) infection relative to animals treated with control antibody. CD8+T cell depletion was comparably well tolerated and did not significantly affect the weight of infected guinea pigs or viral loads in their blood or tissue. However, significantly more viral genomes and transcripts were detected in the placenta and decidua of CD8+T cell depleted dams post-infection. This study corroborates earlier findings made in nonhuman primates that maternal CD4+T cells play a critical role in limiting the severity of primary CMV infection during pregnancy while also revealing that other innate and adaptive immune responses can compensate for an absent CD8+T cell response in α-CD8-treated guinea pigs.Author SummaryCongenital cytomegalovirus infection is a leading cause of adverse pregnancy outcomes and preventable disability in children. Using guinea pigs, a well-established small animal model of congenital infection and intrauterine development, this study tested how depleting T cells affects the course of primary cytomegalovirus infections. Severe illness and high rates of congenital infection were observed when helper CD4+T cells were depleted. The depletion of killer CD8+T cells did not affect the severity of disease or the rate of congenital infection but did increase the amount of virus that was detected in the placenta. A greater understanding how an immune response can prevent the infection of the placenta and developing offspring is needed to inform vaccine and therapeutic development. This study not only describes a new reagent that can be used to study the guinea pig immune system but also sheds new light in how adaptive immunity regulates congenital viral infection.
OPA1 mediates cardiac function and metabolism: in silico and in vivo evidence
Authors: Fong-McMaster Claire , Pulente Serena M. , Kennedy Luke , Smith Tyler K.T. , Myers Stephanie , Kanaan Michel , Karam Charbel , Cope Matthew , Lorenzen-Schmidt Ilka , Goergen Craig J. , Fullerton Morgan D. , Cuperlovic-Culf Miroslava , Mulvihill Erin E. , Harper Mary-Ellen 
Published: August 2024

AbstractOPA1 is an inner mitochondrial membrane protein that mediates diverse signaling processes. OPA1 is important for cardiac function and protects against cardiac insults such as ischemia reperfusion injury. We sought to further assess OPA1 in human and mouse cardiac pathologies, hypothesizing that OPA1 may also function in a protective manner in chronic heart failure. Bioinformatic analyses of histological and transcript data from the GTEx database indicated that OPA1 expression levels vary in the human heart, where elevated OPA1 transcript levels were correlated with fatty acid, branch chain amino acid and contractile gene signatures. To experimentally assess these correlations, mice with a 1.5-fold whole body OPA1 overexpression (OPA1-OE) were subjected to transverse aortic constriction surgery and displayed improved 2D and 4D cardiac functional parameters compared to WT mice. OPA1-OE mice had no induction of fibrotic transcript markers and displayed sustained transcript levels of fatty acid, branch chain amino acid and contractile markers. Maximal oxidative capacity was sustained in both WT and OPA1-OE cardiac myofibers post-TAC. These results further demonstrate the important role of OPA1 in mediating cardiac function and highlight protective signaling pathways.
Synthesis and in vitro evaluation shows disquaramide compounds are a promising class of anti-leishmanial drugs
Authors: Roys Hayden , Arykbayeva Assyl , Friedman Sarah K. , Gifford Gabriel , Palmer Eva R. , Rogers Alex , Tran Emily N. H. , Fry Lucy , Weaver Alexx , Bowlin Anne , Jones Meghan D. , Eledge Michael R. , Boehme Karl W. , Naumiec Gregory R. , Weinkopff Tiffany 
Published: August 2024

ABSTRACTAn increasing number of treatment failures with current pharmaceutics, as well as a lack of a vaccine, demonstrates the need to develop new treatment options for leishmaniasis. Herein, we describe the synthesis and in vitro analysis of 24 disquaramide compounds targeting theLeishmania majorparasite. Of the compounds that were evaluated, six of them (13,19,20,22,24, and26) were capable of significantly decreasing the number of parasites by up to 42% compared to the control by day four. This demonstrates that disquaramides either impair parasite replication or have leishmancidal effects. Additionally, none of the disquaramide compounds tested displayed host cell cytotoxicity. These experiments provide evidence that disquaramides have the potential to be effective anti-leishmanial therapeutics.
Brain structure and activity predicting cognitive maturation in adolescence
Authors: Zhu Junda , Garin Clément M. , Qi Xue-Lian , Machado Anna , Wang Zhengyang , Ben Hamed Suliann , Stanford Terrence R. , Salinas Emilio , Whitlow Christopher T. , Anderson Adam W. , Zhou Xin Maizie , Calabro Finnegan J. , Luna Beatriz , Constantinidis Christos 
Published: August 2024

SummaryCognitive abilities of primates, including humans, continue to improve through adolescence1,2. While a range of changes in brain structure and connectivity have been documented3,4, how they affect neuronal activity that ultimately determines performance of cognitive functions remains unknown. Here, we conducted a multilevel longitudinal study of monkey adolescent neurocognitive development. The developmental trajectory of neural activity in the prefrontal cortex accounted remarkably well for working memory improvements. While complex aspects of activity changed progressively during adolescence, such as the rotation of stimulus representation in multidimensional neuronal space, which has been implicated in cognitive flexibility, even simpler attributes, such as the baseline firing rate in the period preceding a stimulus appearance had predictive power over behavior. Unexpectedly, decreases in brain volume and thickness, which are widely thought to underlie cognitive changes in humans5did not predict well the trajectory of neural activity or cognitive performance changes. Whole brain cortical volume in particular, exhibited an increase and reached a local maximum in late adolescence, at a time of rapid behavioral improvement. Maturation of long-distance white matter tracts linking the frontal lobe with areas of the association cortex and subcortical regions best predicted changes in neuronal activity and behavior. Our results provide evidence that optimization of neural activity depending on widely distributed circuitry effects cognitive development in adolescence.
Dynamic convergence of autism disorder risk genes across neurodevelopment
Authors: Fernandez Garcia Meilin , Retallick-Townsley Kayla , Pruitt April , Davidson Elizabeth , Dai Yi , Fitzpatrick Sarah E. , Sen Annabel , Cohen Sophie , Livoti Olivia , Khan Suha , Dossou Grace , Cheung Jen , Deans P.J. Michael , Wang Zuoheng , Huckins Laura , Hoffman Ellen , Brennand Kristen 
Published: August 2024

ABSTRACTOver a hundred risk genes underlie risk for autism spectrum disorder (ASD) but the extent to which they converge on shared downstream targets to increase ASD risk is unknown. To test the hypothesis that cellular context impacts the nature of convergence, here we apply a pooled CRISPR approach to target 29 ASD loss-of-function genes in human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells, glutamatergic neurons, and GABAergic neurons. Two distinct approaches (gene-level and network-level analyses) demonstrate that convergence is greatest in mature glutamatergic neurons. Convergent effects are dynamic, varying in strength, composition, and biological role between cell types, increasing with functional similarity of the ASD genes examined, and driven by cell-type-specific gene co-expression patterns. Stratification of ASD genes yield targeted drug predictions capable of reversing gene-specific convergent signatures in human cells and ASD-related behaviors in zebrafish. Altogether, convergent networks downstream of ASD risk genes represent novel points of individualized therapeutic intervention.
The Hemopurifier removes extracellular vesicles and microRNAs from renal perfusates following controlled oxygenated rewarming of discarded donor kidneys
Authors: de Necochea Campion Rosalia , Pesqueira Miguel , Vallejos Paul , McCullough Cameron , Bloesch Alessio , La Rosa Steven P. 
Published: August 2024

AbstractKidney transplantation is considered the benchmark treatment for end-stage kidney disease patients. Nevertheless, the demand for donor kidneys is continuously on the rise and the scarcity of suitable kidneys poses a significant hindrance for patients and healthcare providers. One approach is to extend the criteria for the use of kidneys from deceased brain death and deceased circulatory death donors. Use of these organs especially from these extended criteria donors is associated with ischemia reperfusion injury (IRI) and resultant delayed graft function (DGF) as well as increased rates of allograft rejection. One approach to try to lessen these complications as well as increase the time the assessment of organ viability is the use of machine perfusion on recovered kidneys. In this study we obtained perfusates from discarded organs that had undergone Controlled Oxygenated Rewarming. Perfusates were analyzed for extracellular vesicles (EVs), dsDNA associated with EVs and microRNAs. These perfusates were then pumped over the Aethlon Hemopurifier, a plasma separator with an affinity resin containing the lectinGalanthus nivalisagglutinin (GNA). Following treatment with the Hemopurifier, a diminution in extracellular vesicles, dsDNA associated with EVs and microRNAs was observed. These results support a future study of the Aethlon Hemopurifier as part of a machine perfusion circuit to explore if the device decreases these mediators in a dynamic circuit and is associated with improved function of retrieved kidneys.
Musicality enhances selective attention: spatiotemporal insights from precise separation of simultaneous neural responses
Authors: Manting Cassia Low , Pantazis Dimitrios , Gabrieli John , Lundqvist Daniel 
Published: August 2024

1.ABSTRACTWe precisely resolved simultaneous neural responses to their driving stimuli and classified them to different selective attention conditions towards specific melodies within mixtures. Magnetoencephalographic findings reveal the influence of participants’ musicality and task performance on the recruitment of cortical regions in bottom-up and top-down attentional processes. Across parietal regions, musicality and performance correlated positively with top-down attention at the left hemisphere, but negatively with bottom-up attention at the right. In the right prefrontal cortex, individuals who maintained selective attention over the tone duration performed better and were more musical. These results suggest that musical training boosts performance by enhancing top-down attention, reducing bottom-up distractions, and sustaining selective attention overtime, with these effects mediated by the frontoparietal cortex. This work advances our understanding of neural selective attention mechanisms in complex soundscapes and underscores the potential of musical training for cognitive enhancement. Our breakthrough approach effectively captures cognitive effects with frequency-tagging, creating new possibilities for scientific applications.
Decoding protein glycosylation by an integrative mass spectrometry-basedde novosequencing strategy
Authors: Gao Jing , Chen Hongxu , Yin Hongrui , Chen Xin , Yang Zhicheng , Wang Yuqiu , Wu Jianhong , Tian Yinping , Shao Hong , Wen Liuqing , Zhou Hu 
Published: August 2024

AbstractGlycoproteins, representing over 50% of human proteins and most biopharmaceuticals, are crucial for regulating various biological processes. The complexity of multiple glycosylation sites, often leading to incomplete sequence coverage and ambiguous glycan modification profiles. Here, we developed an integrative mass spectrometry-based approach for decoding unknown glycoproteins, which is featured with the combination of deglycosylation-mediatedde novosequencing with glycosylation site characterization. We utilized enzymatic deglycosylation ofN-/O-glycan to achieve comprehensive sequence coverage. Additionally, EThcD fragmentation enables the identification of high-quality long peptides, facilitating precise protein assembly. We subsequently applied this method tode novosequencing of the highly glycosylated therapeutic fusion protein Etanercept (Enbrel®). We also sequenced three new tumor necrosis factor receptor (TNFR): Fc-fusion biologics with largely unknown sequences, unveiling subtle distinctions in the primary sequences. Furthermore, we characterizedN- andO-glycosylation modifications of these proteins at subunit, glycopeptide, and glycan levels. This strategy bridges the gap between thede novosequencing and glycosylation modification, providing complete information of the primary structure and glycosylation modifications for glycoproteins. Notably, our method could be a robust solution for accurate sequencing of the glycoproteins and has practical value not only in basic research but also in the biopharmaceutical industry.