bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine-Learning Powered Optoacoustic Sensor for Diabetes Progression
Authors: Mohajerani Pouyan , Aguirre Juan , Omar Murad , He Hailong , Karlas Angelos , Fasoula Nikolina-Alexia , Lutz Jessica , Kallmayer Michael , Eckstein Hans-Henning , Ziegler Anette-Gabriele , Füchtenbusch Martin , Ntziachristos Vasilis 
Published: March 2021

AbstractThe assessment of diabetes severity relies primarily on a count of clinical complications to empirically characterize disease. Disease staging based on clinical complications also employs a scoring system that may not be optimally suited for analysis of earlier stages of diabetes development or for monitoring smaller increments of disease progress with high precision. We propose a novel sensor, which goes beyond the abilities of current state-of-the-art approaches and introduces a new concept in the assessment of biomedical markers by means of ultra-broadband optoacoustic detection. Being insensitive to photon scattering, the new sensor can resolve optical biomarkers in fine detail and as a function of depth and relates epidermal and dermal morphological and micro-vascular density features to diabetes state. We demonstrate basic sensor characteristics in phantoms and examine the novel sensing concept presented in a pilot study using data from 86 participants (20 healthy and 66 diabetic) at an ultra-wide optoacoustic bandwidth of 120 MHz. Machine learning based on ensemble trees was developed and trained in a supervised fashion and subsequently used to examine the relation of sensor data to disease severity, in particular as it associates to diabetes without complications vs. diabetic neuropathy or atherosclerotic cardiovascular disease. We also investigated the sensor performance in relation to HbA1C values. The proposed method achieved statistically significant detection in all different patient groups. The effect of technical parameters, in particular sensor area size and the time window of optoacoustic signals used in data training were also examined in measurements from phantoms and humans. We discuss how optoacoustic sensors fundamentally solve limitations present in optical sensing and, empowered by machine learning, open a new chapter in non-invasive portable sensing for biomedical applications.
High risk of patient self-inflicted lung injury in COVID-19 with frequently encountered spontaneous breathing patterns: a computational modelling study
Authors: Weaver Liam , Das Anup , Saffaran Sina , Yehya Nadir , Scott Timothy E. , Chikhani Marc , Laffey John G. , Hardman Jonathan G. , Camporota Luigi , Bates Declan G. 
Published: March 2021

AbstractBackgroundThere is on-going controversy regarding the potential for increased respiratory effort to generate patient self-inflicted lung injury (P-SILI) in spontaneously breathing patients with COVID-19 acute hypoxaemic respiratory failure. However, direct clinical evidence linking increased inspiratory effort to lung injury is scarce. We adapted a computational simulator of cardiopulmonary pathophysiology to quantify the mechanical forces that could lead to P-SILI at different levels of respiratory effort. In accordance with recent data, the simulator parameters were manually adjusted to generate a population of 10 patients that recapitulate clinical features exhibited by certain COVID-19 patients, i.e. severe hypoxaemia combined with relatively well-preserved lung mechanics, being treated with supplemental oxygen.ResultsSimulations were conducted at tidal volumes (VT) and respiratory rates (RR) of 7 ml/kg and 14 breaths/min (representing normal respiratory effort) and at VT/RR of 7/20, 7/30, 10/14, 10/20 and 10/30 ml/kg / breaths/min. While oxygenation improved with higher respiratory efforts, significant increases in multiple indicators of the potential for lung injury were observed at all higher VT/RR combinations tested. Pleural pressure swing increased from 12.0±0.3 cmH2O at baseline to 33.8±0.4 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 46.2±0.5 cmH2O at 10 ml/kg/30 breaths/min. Transpulmonary pressure swing increased from 4.7±0.1 cmH2O at baseline to 17.9±0.3 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 24.2±0.3 cmH2O at 10 ml/kg/30 breaths/min. Total lung strain increased from 0.29±0.006 at baseline to 0.65±0.016 at 10 ml/kg/30 breaths/min. Mechanical power increased from 1.6±0.1 J/min at baseline to 12.9±0.2 J/min at VT/RR of 7 ml/kg/30 breaths/min, and to 24.9±0.3 J/min at 10 ml/kg/30 breaths/min. Driving pressure increased from 7.7±0.2 cmH2O at baseline to 19.6±0.2 at VT/RR of 7 ml/kg/30 breaths/min, and to 26.9±0.3 cmH2O at 10 ml/kg/30 breaths/min.ConclusionsOur results suggest that the forces generated by increased inspiratory effort commonly seen in COVID-19 acute hypoxaemic respiratory failure are comparable with those that have been associated with ventilator-induced lung injury during mechanical ventilation. Respiratory efforts in these patients should be carefully monitored and controlled to minimise the risk of lung injury.
Neural correlates of metacognition across the adult lifespan
Authors: Overhoff Helen , Ko Yiu Hong , Feuerriegel Daniel , Fink Gereon R. , Stahl Jutta , Weiss Peter H. , Bode Stefan , Niessen Eva 
Published: March 2021

AbstractMetacognitive accuracy describes the degree of overlap between the subjective perception of one’s decision accuracy (i.e., confidence) and objectively observed performance. With older age, the need for accurate metacognitive evaluation increases; however, error detection rates typically decrease. We investigated the effect of ageing on metacognitive accuracy using event-related potentials (ERPs) reflecting error detection and confidence: the error/correct negativity (Ne/c) and the error/correct positivity (Pe/c). Sixty-five healthy adults (20 to 76 years) completed a complex perceptual task and provided confidence ratings. We found that metacognitive accuracy declined with age beyond the expected decline in task performance, while the adaptive adjustment of behaviour was well preserved. Pe/camplitudes varied by confidence rating, but they did not mirror the reduction in metacognitive accuracy. Ne/camplitudes decreased with age except for high confidence correct responses. The results suggest that age-related difficulties in metacognitive evaluation could be related to an impaired integration of decision accuracy and confidence information processing. Ultimately, training the metacognitive evaluation of fundamental decisions in older adults might constitute a promising endeavour.
Strong genetic structure and limited connectivity among populations of Clark’s Anemonefish (Amphiprion clarkii) in the centre of marine biodiversity
Authors: Ducret Hugo , Timm Janne , Moreno Melina Rodríguez , Huyghe Filip , Kochzius Marc 
Published: March 2021

ABSTRACTPopulations of anemonefish species often show signs of local isolation due limited dispersal potential and oceanographic conditions. Additionally, anthropogenic pressure, such as overharvesting and coral reef exploitation causes reduced population size, eventually leading to local extinction. The understanding of the genetic population structure, as well as the influence of both historical and current connectivity, is required to design effective marine protected area (MPA) networks. In this study, the genetic structure of Clark’s Anemonefish (Amphiprion clarkii) populations of the Indo-Malay Archipelago (IMA) is assessed through mitochondrial control region (mtCR) sequences and nuclear microsatellites. Results provided evidence of a significant genetic structure (mtCR: Φst= 0.42039, Φct= 0.63852; microsatellites: Fst= 0.01449, Fct= 0.05199). Genetic breaks were identified among Western (Padang Karimunjawa), Central (Sulawesi, Borneo, Bali, Komodo, Timor), and Eastern (Biak) IMA populations, which matches with patterns obtained for congeneric and other coral reef taxa. Due to the restricted connectivity among these three regions, it is suggested to consider them as separate management areas in the design of MPA networks.
Dynamic plasticity within the EMT spectrum, rather than static mesenchymal traits, drives tumor heterogeneity and metastatic progression of breast cancers
Authors: Brown Meredith S. , Abdollahi Behnaz , Wilkins Owen M. , Chakraborty Priyanka , Ognjenovic Nevena B. , Muller Kristen E. , Jolly Mohit Kumar , Hassanpour Saeed , Pattabiraman Diwakar R. 
Published: March 2021

AbstractThe Epithelial-to-Mesenchymal Transition (EMT) is a developmental cellular program frequently coopted by cancer cells1and is a key contributor to both heterogeneity in solid tumors2–4and later stage chemo-resistance and metastasis5,6. Rather than being a switch from an epithelial to a mesenchymal state, increasing evidence points to the existence of intermediate EMT states, wherein cells co-express both epithelial and mesenchymal traits7–13. Multiple stable intermediate EMT states possessing unique characteristics exist across the EMT spectrum7,8,14,15, contributing to the complex heterogeneity of tumors to promote metastasis16. While much work has been carried out identifying and characterizing EMT-inducing transcription factors17–20, the transcriptional and epigenetic networks responsible for the stability and maintenance of the midpoints along the EMT spectrum are poorly defined. In addition, there are currently no approaches to identifying and quantifying intermediate EMT subpopulations within patient tumors to evaluate their prognostic significance. Using clonally isolated derivatives of the SUM149PT breast cancer cell line, we systematically interrogate how each EMT state independently contributes to heterogeneity and influences metastatic progression, uncovering the role of RUNX2 in stabilizing certain intermediate states. Using SUM149PT-derived tumors as a training set, we develop an entropy-based model to quantify phenotypic heterogeneity and EMT status. Remarkably, the majority of cell states captured in the SUM149PT model are represented in a selection of patient tumors, laying the foundation for quantification of epithelial-mesenchymal heterogeneity and understanding the role of the intermediate EMT state in tumor progression.
The unphosphorylated form of the PAQosome core subunit RPAP3 binds ribosomal preassembly complexes to modulate ribosome biogenesis
Authors: Pinard Maxime , Cloutier Philippe , Poitras Christian , Gauthier Marie-Soleil , Coulombe Benoit 
Published: March 2021

AbstractThe PAQosome (Particle for Arrangement of Quaternary structure) is a twelve-subunit HSP90 co-chaperone involved in the biogenesis of several human protein complexes. Two mechanisms of client selection have previously been identified, namely the selective recruitment of specific adaptors and the differential use of homologous core subunits. Here, we describe a third client selection mechanism by showing that RPAP3, one of the core PAQosome subunits, is phosphorylated at several Ser residues in HEK293 cells. Affinity purification coupled with mass spectrometry (AP-MS) using expression of tagged RPAP3 with single phospho-null mutations at Ser116, Ser119 or Ser121 reveals binding of the unphosphorylated form to several proteins involved in ribosome biogenesis.In vitrophosphorylation assays indicate that the kinase CK2 phosphorylates these RPAP3 residues. This finding is supported by data showing that pharmacological inhibition of CK2 enhances binding of RPAP3 to ribosome preassembly factors in AP-MS experiments. Moreover, silencing of PAQosome subunits interferes with ribosomal assembly factors’ interactome. Altogether, these results indicate that RPAP3 phosphate group addition/removal at specific residues modulates binding to subunits of preribosomal complexes and allows speculating that PAQosome posttranslational modifications is a mechanism of client selection.
A genomic and morphometric analysis of alpine bumblebees: ongoing reductions in tongue length but no clear genetic component
Authors: Christmas Matthew J. , Jones Julia C. , Olsson Anna , Wallerman Ola , Bunikis Ignas , Kierczak Marcin , Whitley Kaitlyn M. , Sullivan Isabel , Geib Jennifer C. , Miller-Struttmann Nicole E. , Webster Matthew T. 
Published: March 2021

ABSTRACTOver the last six decades, populations of the bumblebeesBombus sylvicolaandBombus balteatusin Colorado have experienced decreases in tongue length, a trait important for plant-pollinator mutualisms. It has been hypothesized that this observation reflects selection resulting from shifts in floral composition under climate change. Here we used morphometrics and population genomics to determine whether morphological change is ongoing, investigate the genetic basis of morphological variation, and analyze population structure in these populations. We generated a genome assembly ofB. balteatus. We then analyzed whole-genome sequencing data and morphometric measurements of 580 samples of both species from seven high-altitude localities. Out of 281 samples originally identified asB. sylvicola, 67 formed a separate genetic cluster comprising a newly-discovered cryptic species (“incognitus”). However, an absence of genetic structure within species suggests that gene flow is common between mountains. We found a significant decrease in tongue length between bees collected between 2012-2014 and in 2017, indicating that morphological shifts are ongoing. We did not discover any genetic associations with tongue length, but a SNP related to production of a proteolytic digestive enzyme was implicated in body size variation. We identified evidence of covariance between kinship and both tongue length and body size, which is suggestive of a genetic component of these traits, although it is possible that shared environmental effects between colonies are responsible. Our results provide evidence for ongoing modification of a morphological trait important for pollination and indicate that this trait likely has a complex genetic and environmental basis.
Efficacy of Distributed Training Depends on the Dorso-Lateral Striatum
Authors: Mastrorilli Valentina , Centofante Eleonora , Antonelli Federica , Rinaldi Arianna , Mele Andrea 
Published: March 2021

AbstractDistributed training has long been known to lead to more robust memory formation as compared to massed training. Here we demonstrate that distributed and massed training differentially engage the dorsolateral and dorsomedial striatum and optogenetic priming of dorsolateral striatum can artificially increase the robustness of massed training to the level of distributed training, identifying a novel therapeutic avenue for memory enhancement.
An optimal population code for global motion estimation in local direction-selective cells
Authors: Henning Miriam , Ramos-Traslosheros Giordano , Gür Burak , Silies Marion 
Published: March 2021

AbstractNervous systems allocate computational resources to match stimulus statistics. However, the physical information that needs to be processed depends on the animal’s own behavior. For example, visual motion patterns induced by self-motion provide essential information for navigation. How behavioral constraints affect neural processing is not known. Here we show that, at the population level, local direction-selective T4/T5 neurons inDrosophilarepresent optic flow fields generated by self-motion, reminiscent to a population code in retinal ganglion cells in vertebrates. Whereas in vertebrates four different cell types encode different optic flow fields, the four uniformly tuned T4/T5 subtypes described previously represent a local snapshot. As a population, six T4/T5 subtypes encode different axes of self-motion. This representation might serve to efficiently encode more complex flow fields generated during flight. Thus, a population code for optic flow appears to be a general coding principle of visual systems, but matching the animal’s individual ethological constraints.
Investigating temperature effects on coastal microbial populations and trophic interactions with 16S and 18S rRNA metabarcoding
Authors: Anderson Sean R. , Chisholm Margot , Harvey Elizabeth L. 
Published: March 2021

SummaryTemperature is a universal driver of microbial life, with rising sea surface temperatures expected to differentially influence the physiology, biodiversity, and distribution of bacteria and plankton. The impact of ocean warming on microbial interactions remains unclear, despite the importance of these relationships for ecosystem functioning. We employed weekly to monthly 18S and 16S rRNA gene amplicon metabarcoding over a full year (33 d) in a subtropical estuary, investigating microbial population dynamics and network interactions with respect to a temperature gradient (9–31°C). Certain microbes (e.g., Acidimicrobiia, Nitrososphaeria, and Syndiniales) increased in relative abundance with rising temperatures (Spearman ρ > 0.69), whereas other groups (e.g., Alpha- and Gammaproteobacteria, Bacillariophyta, and Dinophyceae) slightly decreased, became saturated, or remained stable. With network analysis, we observed an increase in 18S– 18S interactions in warm (23–31°C) vs. cold (<23°C) temperatures, largely involving Syndiniales, Bacillariophyta, and Dinophyceae ASVs. Bacteria ASVs were more connected to other microbes (higher degree and centrality) and became more prominent in the cold network, highlighted by well-established cross-domain relationships (e.g., diatom–bacteria) and positive interactions among bacteria (e.g., SAR11 and Rhodobacterales). These efforts highlight the types of interactions that may be more common under changing temperatures, with implications for modeling biogeochemistry and assessing ecosystem health.
Lichen fungi do not depend on the alga for ATP production
Authors: Tagirdzhanova Gulnara , McCutcheon John P. , Spribille Toby 
Published: March 2021

AbstractLichen fungi live in a symbiotic association with unicellular phototrophs and have no known aposymbiotic stage. A recent study postulated that some of them have lost mitochondrial oxidative phosphorylation and rely on their algal partners for ATP. This claim originated from an apparent lack ofATP9, a gene encoding one subunit of ATP synthase, from a few mitochondrial genomes. Here we show that while these fungi indeed have lost the mitochondrialATP9, each retain a nuclear copy of this gene. Our analysis reaffirms that lichen fungi produce their own ATP.
Identification and drug-induced reversion of molecular signatures of Alzheimer’s disease onset and progression inAppNL-G-F,AppNL-Fand 3xTg-AD mouse models
Authors: Pauls Eduardo , Bayod Sergi , Mateo Lídia , Alcalde Víctor , Juan-Blanco Teresa , Saido Takaomi C , Saito Takashi , Berrenguer-Llergo Antoni , Attolini Camille Stephan-Otto , Gay Marina , de Oliveira Eliandre , Duran-Frigola Miquel , Aloy Patrick 
Published: March 2021

AbstractAlzheimer’s disease (AD) is the most common form of dementia. Over fifty years of intense research have revealed many key elements of the biology of this neurodegenerative disorder. However, our understanding of the molecular bases of the disease is still incomplete, and the medical treatments available for AD are mainly symptomatic and hardly effective. Indeed, the robustness of biological systems has revealed that the modulation of a single target is unlikely to yield the desired outcome and we should therefore move from gene-centric to systemic therapeutic strategies. Here we present the complete characterization of three murine models of AD at different stages of the disease (i.e. onset, progression and advanced). To identify genotype-to-phenotype relationships, we combine the cognitive assessment of these mice with histological analyses and full transcriptional and protein quantification profiling of the hippocampus. Comparison of the gene and protein expression trends observed in AD progression and physiological aging revealed certain commonalities, such as the upregulation of microglial and inflammation markers. However, although AD models show accelerated aging, other factors specifically associated with Aβ pathology are involved. Despite the clear correlation between mRNA and protein levels of the dysregulated genes, we discovered a few proteins whose abundance increases with AD progression, while the corresponding transcript levels remain stable. Indeed, we show that at least two of these proteins, namely lfit3 and Syt11, co-localize with Aβ plaques in the brain. Finally, we derived specific Aβ-related molecular AD signatures and looked for drugs able to globally revert them. We found two NSAIDs (dexketoprofen and etodolac) and two anti-hypertensives (penbutolol and bendroflumethiazide) that overturn the cognitive impairment in AD mice while reducing Aβ plaques in the hippocampus and partially restoring the physiological levels of AD signature genes to wild-type levels.TeaserThe comprehensive characterization of three AD mouse models reveals disease signatures that we used to identify approved drugs able to modify the etiology of the pathology and overturn cognitive impairment.
The mayfly subimago explained. The regulation of metamorphosis in Ephemeroptera
Authors: Kamsoi Orathai , Ventos-Alfonso Alba , Almudi Isabel , Casares Fernando , Belles Xavier 
Published: March 2021

ABSTRACTIn the Paleozoic era, more than 400 million years ago, insects continued molting after forming functional wings. Today, however, all flying insects stop molting after metamorphosis when they become fully winged. The only exception is the mayflies (Ephemeroptera), which molt in the subimago, a flying intermediate stage between the nymph and the adult. However, the identity and homology of the subimago remains underexplored. Debate remains regarding whether this stage represents a modified nymph, an adult, or a pupa like that of butterflies. Another relevant question is why do mayflies maintain the subimago stage despite the risk of molting fragile membranous wings. These questions have intrigued numerous authors but nonetheless, clear answers have not yet been found. However, by combining morphological studies, hormonal treatments, and molecular analysis in the mayfly speciesCloeon dipterum, we found new answers to these old questions. We observed that treatment with a juvenile hormone analog in the last nymphal instar stimulated the expression ofKr-h1gene and reduced that ofE93, which suppress and trigger metamorphosis, respectively. Consequently, the subimago is not formed in these treated mayflies. This indicates that metamorphosis is determined prior to the formation of the subimago, which must therefore be considered an instar of the adult stage. We also observed that the forelegs dramatically grow between the last nymphal instar, the subimago, and the adult. This necessary growth is spread over the last two stages, which could explain, at least in part, the adaptive sense of the subimago.