bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards rainy high Arctic winters: how ice-encasement impacts tundra plant phenology, productivity and reproduction
Authors: Le Moullec Mathilde , Hendel Anna-Lena , Petit Bon Matteo , Jónsdóttir Ingibjörg Svala , Varpe Øystein , van der Wal René , Beumer Larissa Teresa , Layton-Matthews Kate , Isaksen Ketil , Hansen Brage Bremset 
Published: June 2021

AbstractThe Arctic is warming rapidly, with winters warming up to seven times as fast as summers in some regions. Warm spells in winter lead to more frequent extreme rain-on-snow events that alter snowpack conditions and can encapsulate tundra vegetation in ‘basal ice’ (‘icing’) for several months. However, tundra climate change studies have mainly focused on summer warming. Here, we investigate icing effects on vascular plant phenology, productivity, and reproduction in a pioneer field experiment in high Arctic Svalbard, simulating rain-on-snow and resultant icing in five consecutive winters, assessing vascular plant responses throughout each subsequent growing season. We also tested whether icing responses were modified by experimentally increased summer temperatures. Icing alone delayed early phenology of the dominant shrub,Salix polaris, but with evidence for a ‘catch-up’ (through shortened developmental phases and increased community-level primary production) later in the growing season. This compensatory response occurred at the expense of delayed seed maturation and reduced community-level inflorescence production. Both the phenological delay and allocation trade-offs were associated with icing-induced lags in spring thawing and warming of the soil, crucial to regulating plant nutrient availability and acquisition. Experimental summer warming modified icing effects by advancing and accelerating plant phenology (leaf and seed development), thus increasing primary productivity already early in the growing season, and partially offsetting negative icing effects on reproduction. Thus, winter and summer warming must be considered simultaneously to predict tundra plant climate change responses. Our findings demonstrate that winter warm spells can shape high Arctic plant communities to a similar level as summer warming. However, the absence of accumulated effects over the years reveals an overall resistant community which contrasts with earlier studies documenting major die-off. As rain-on-snow events will be rule rather than exception in most Arctic regions, we call for similar experiments in coordinated circumpolar monitoring programmes across tundra plant communities.
Consciousness is supported by near-critical cortical electrodynamics
Authors: Toker Daniel , Pappas Ioannis , Lendner Janna D. , Frohlich Joel , Mateos Diego M. , Muthukumaraswamy Suresh , Carhart-Harris Robin , Paff Michelle , Vespa Paul M. , Monti Martin M. , Sommer Friedrich T. , Knight Robert T. , D’Esposito Mark 
Published: June 2021

Mounting evidence suggests that during conscious states, the electrodynamics of the cortex are poised near a critical point or phase transition, and that this near-critical behavior supports the vast flow of information through cortical networks during conscious states. Here, for the first time, we empirically identify the specific critical point near which conscious cortical dynamics operate as the edge-of-chaos critical point, or the boundary between periodicity/stability and chaos/instability. We do so by applying the recently developed modified 0-1 chaos test to electrocorticography (ECoG) and magne-toencephalography (MEG) recordings from the cortices of humans and macaques across normal waking, generalized seizure, GABAergic anesthesia, and psychedelic states. Our evidence suggests that cortical information processing is disrupted during unconscious states because of a transition of cortical dynamics away from this critical point; conversely, we show that psychedelics may increase the information-richness of cortical activity by tuning cortical electrodynamics closer to this critical point. Finally, we analyze clinical electroencephalography (EEG) recordings from patients with disorders of consciousness (DOC), and show that assessing the proximity of cortical electrodynamics to the edge-of-chaos critical point may be clinically useful as a new biomarker of consciousness.Significance StatementWhat changes in the brain when we lose consciousness? One possibility is that the loss of consciousness corresponds to a transition of the brain’s electric activity away from edge-of-chaos criticality, or the knife’s edge in between stability and chaos. Recent mathematical developments have produced novel tools for testing this hypothesis, which we apply for the first time to cortical recordings from diverse brain states. We show that the electric activity of the cortex is indeed poised near the boundary between stability and chaos during conscious states and transitions away from this boundary during unconsciousness, and that this transition disrupts cortical information processing.
Solute carrier 5A5 regulates systemic glucose homeostasis by mediating glucose absorption in the Drosophila midgut
Authors: Li Yue , Wang Weidong , Lim Hui-Ying 
Published: June 2021

AbstractThe small intestine is the first organ that is exposed to and absorbs dietary glucose and thus represents the first of a continuum of events that modulates normal systemic glucose homeostasis. A better understanding of the regulation of intestinal glucose transporters is therefore pertinent to our efforts in curbing metabolic disorders. However, so far, the mechanisms known to regulate SGLT1, the primary intestinal glucose transporter, are mainly elucidated from in vitro studies. The Drosophila midgut, functional equivalence of the small intestine, could serve as an efficient in vivo model system for studying intestinal glucose transporter regulation; however, no glucose transporter has yet been identified in the midgut. Here, we report that the Drosophila Solute Carrier 5A5 (dSLC5A5) is homologous to SGLT1 and is highly expressed in the midgut. The knockdown of dSLC5A5 decreases systemic and circulating sugar levels and decreases glucose uptake into the enterocytes. In contrary, the overexpression of dSLC5A5 elevates systemic and circulating sugar levels and promotes glucose uptake into the enterocytes. We show that dSLC5A5 undergoes dynamin-dependent endocytosis in the enterocyte apical membrane, and that dSLC5A5 endocytosis is essential for the glucose uptake capability of dSLC5A5. Moreover, we provide evidence supporting that intracellular lysosomal degradation of endocytosed dSLC5A5 plays a significant role in the maintenance of dSLC5A5 level in the enterocyte apical membrane. We further show that short-term exposure to glucose upregulates SLC5A5 abundance in the enterocyte apical membrane. Finally, we show that the loss or gain of dSLC5A5 ameliorates or exacerbates the high sugar diet (HSD)-mediated glucose metabolic defects. Together, our studies uncovered the first Drosophila glucose transporter in the midgut and reveal new mechanisms that regulate glucose transporters in the enterocyte apical membranes.
Drug-dependent morphological transitions in spherical and worm-like polymeric micelles define stability and pharmacological performance of micellar drugs
Authors: Lim Chaemin , Ramsey Jacob D. , Hwang Duhyeong , Teixeira Susana C. M. , Poon Chi-Duen , Strauss Joshua D , Sokolsky-Papkov Marina , Kabanov Alexander V. 
Published: June 2021

AbstractSignificant advances in physicochemical properties of polymeric micelles enable optimization of therapeutic drug efficacy, supporting nanomedicine manufacturing and clinical translation. Yet, the effect of micelle morphology on pharmacological efficacy has not been adequately addressed. We addressed this gap by assessing pharmacological efficacy of polymeric micelles with spherical and worm-like morphologies. We observed that poly(2-oxazoline)-based polymeric micelles can be elongated over time from a spherical structure to worm-like structure, with elongation influenced by several conditions, including the amount and type of drug loaded into the micelles. We further evaluated the role of different morphologies of olaparib micelles on pharmacological performance against a triple-negative breast cancer tumor (TNBC) model. Spherical micelles accumulated rapidly in the tumor tissue while retaining large amounts of drug; worm-like micelles accumulated more slowly and only upon releasing significant amounts of drug. These findings suggest that the dynamic character of the drug–micelle structure and the micelle morphology play a critical role in pharmacological performance, and that spherical micelles are better suited for systemic delivery of anticancer drugs to tumors when drugs are loosely associated with the polymeric micelles.
Generalized additive models to analyze non-linear trends in biomedical longitudinal data using R: Beyond repeated measures ANOVA and Linear Mixed Models
Authors: Mundo Ariel I. , Muldoon Timothy J. , Tipton John R. 
Published: June 2021

1AbstractIn biomedical research, the outcome of longitudinal studies has been traditionally analyzed using therepeated measures analysis of variance(rm-ANOVA) or more recently,linear mixed models(LMEMs). Although LMEMs are less restrictive than rm-ANOVA as they can work with unbalanced data and non-constant correlation between observations, both methodologies assume a linear trend in the measured response. It is common in biomedical research that the true trend response is nonlinear and in these cases the linearity assumption of rm-ANOVA and LMEMs can lead to biased estimates and unreliable inference.In contrast, GAMs relax the linearity assumption of rm-ANOVA and LMEMs and allow the data to determine the fit of the model while also permitting incomplete observations and different correlation structures. Therefore, GAMs present an excellent choice to analyze longitudinal data with non-linear trends in the context of biomedical research. This paper summarizes the limitations of rm-ANOVA and LMEMs and uses simulated data to visually show how both methods produce biased estimates when used on data with non-linear trends. We present the basic theory of GAMs and using reported trends of oxygen saturation in tumors, we simulate example longitudinal data (2 treatment groups, 10 subjects per group, 5 repeated measures for each group) to demonstrate their implementation in R. We also show that GAMs are able to produce estimates with non-linear trends even when incomplete observations exist (with 40% of the simulated observations missing). To make this work reproducible, the code and data used in this paper are available at:https://github.com/aimundo/GAMs-biomedical-research.
PD-1 checkpoint blockade disrupts CD4 T cell regulated adaptive B cell tolerance to foreign antigens
Authors: Dufaud Chad R. , Shuparski Andrew G. , Higgins Brett W. , McHeyzer-Williams Louise J. , McHeyzer-Williams Michael G. 
Published: June 2021

SUMMARYAdaptive B cell immunity to environmental antigens must be regulated by multiple CD4 T cell dependent tolerance mechanisms. Using integrated single cell strategies, we demonstrate that acute PD-1 blockade induces extensive and selective local anti-inflammatory IgG1 plasma cell (PC) differentiation. Expansion of pre-existing IgG1 germinal center (GC) B cell and enhanced GC programming without memory B cell involvement reveals an isotype-specific GC checkpoint that blocks steady-state IgG1 antibody maturation. While there was no adjuvant impact on immunization, acute PD-1 checkpoint blockade exaggerates anti-commensal IgG1 antibody production, alters microbiome composition and exerts its action in a CD4 T cell dependent manner. These findings reveal a PD-1 controlled adaptive B cell tolerance checkpoint that selectively constrains maturation of pre-existing anti-inflammatory antibodies to prevent over-reaction to steady-state foreign antigens.In BriefPD-1 controls an adaptive B cell tolerance checkpoint in steady-state germinal centers to inhibit the maturation and production of IgG1 antibody with pre-existing foreign specificities.Highlights– Acute PD-1 blockade induces extensive IgG1 PC differentiation at homeostasis– PD-1 blockade releases an IgG1 GC B cell checkpoint that drives expansion and PC formation– No adjuvant effect on foreign antigen but expansion of pre-existing IgG1 specificities to non-self– PD-1 exerts CD4 T cell dependent tolerance in the GC to restrict IgG1 maturation to non-selfGraphical Abstract
A Novel Local Explainability Approach for Spectral Insight into Raw Eeg-Based Deep Learning Classifiers
Authors: Ellis Charles A. , Miller Robyn L. , Calhoun Vince D. 
Published: June 2021

ABSTRACTThe frequency domain of electroencephalography (EEG) data has developed as a particularly important area of EEG analysis. EEG spectra have been analyzed with explainable machine learning and deep learning methods. However, as deep learning has developed, most studies use raw EEG data, which is not well-suited for traditional explainability methods. Several studies have introduced methods for spectral insight into classifiers trained on raw EEG data. These studies have provided global insight into the frequency bands that are generally important to a classifier but do not provide local insight into the frequency bands important for the classification of individual samples. This local explainability could be particularly helpful for EEG analysis domains like sleep stage classification that feature multiple evolving states. We present a novel local spectral explainability approach and use it to explain a convolutional neural network trained for automated sleep stage classification. We use our approach to show how the relative importance of different frequency bands varies over time and even within the same sleep stages. Furthermore, to better understand how our approach compares to existing methods, we compare a global estimate of spectral importance generated from our local results with an existing global spectral importance approach. We find that the δ band is most important for most sleep stages, though β is most important for the non-rapid eye movement 2 (NREM2) sleep stage. Additionally, θ is particularly important for identifying Awake and NREM1 samples. Our study represents the first approach developed for local spectral insight into deep learning classifiers trained on raw EEG time series.
Measuring the metabolic evolution of glioblastoma throughout tumor development, regression, and recurrence with hyperpolarized magnetic resonance
Authors: Salzillo Travis C. , Mawoneke Vimbai , Weygand Joseph , Shetty Akaanksh , Gumin Joy , Zacharias Niki M. , Gammon Seth T. , Piwnica-Worms David , Fuller Gregory N. , Logothetis Christopher J. , Lang Frederick F. , Bhattacharya Pratip K. 
Published: June 2021

SummaryRapid diagnosis and therapeutic monitoring of aggressive diseases such as glioblastoma can improve patient survival by providing physicians the time to optimally deliver treatment. This research tested whether metabolic imaging with hyperpolarized MRI could detect changes in tumor progression faster than conventional anatomic MRI in patient-derived glioblastoma murine models. To capture the dynamic nature of cancer metabolism, hyperpolarized MRI, NMR spectroscopy, and immunohistochemistry were performed at several time-points during tumor development, regression, and recurrence. Hyperpolarized MRI detected significant changes of metabolism throughout tumor progression whereas conventional MRI was less sensitive. This was accompanied by aberrations in amino acid and phospholipid lipid metabolism and MCT1 expression. Hyperpolarized MRI can help address clinical challenges such as identifying malignant disease prior to aggressive growth, differentiating pseudoprogression from true progression, and predicting relapse. The individual evolution of these metabolic assays as well as their correlations with one another provides context for further academic research.
Including imprecisely georeferenced specimens improves accuracy of species distribution models and estimates of niche breadth
Authors: Smith Adam B. , Murphy Stephen J. , Henderson David , Erickson Kelley D. 
Published: June 2021

AbstractAimMuseum and herbarium specimen records are frequently used to assess species’ conservation status and responses to climate change. Typically, occurrences with imprecise geolocality information are discarded because they cannot be matched confidently to environmental conditions, and are thus expected to increase uncertainty in downstream analyses. However, using only precisely georeferenced records risks undersampling of species’ environmental and geographic distributions. We present two related methods to allow the use of imprecisely georeferenced occurrences in biogeographic analysis.InnovationOur two procedures assign imprecise records to the 1) locations or 2) climates that are closest to the geographic or environmental centroid of the precise records of a species. For virtual species, including imprecise records alongside precise records improved the accuracy of ecological niche models projected to the present and the future, especially for species with~20 or fewer precise occurrences. Using only precise records underestimates loss in suitable habitat and overestimates the amount of suitable habitat in both the present and future. Including imprecise records also improves estimates of niche breadth and extent of occurrence. An analysis of 44 species of North AmericanAsclepias(Apocynaceae) yielded similar results.Main conclusionsExisting studies examining the effects of spatial imprecision compare outcomes based on precise records to the same records with spatial error added to them. However, in real-world cases, analysts possess a mix of precise and imprecise records and must decide whether to retain or discard the latter. Discarding imprecise records can undersample species’ geographic and environmental distributions and lead to mis-estimation of responses to past and future climate change. Our method, for which we provide a software implementation in the enmSdmX package for R, is simple to employ and can help leverage the large number of specimen records that are typically deemed “unusable” because of spatial imprecision in their geolocation.
Spatial neglect in the digital age – Influence of presentation format on patients’ test behavior
Authors: Rosenzopf Hannah , Sperber Christoph , Wortha Franz , Wiesen Daniel , Muth Annika , Klein Elise , Möller Korbinian , Karnath Hans-Otto 
Published: June 2021

AbstractComputerization of diagnostic neglect tests can deepen our knowledge of neglect specific abnormalities, by effortlessly providing additional behavioral markers that are hardly extractable from existing paper-and-pencil versions. However, so far it is not known whether the digitization and/or a change in size format impact neglect patients’ search behavior and test scores and thus require adjustments of cut-off criteria. We compared the Center of cancellation (CoC) measure of right hemisphere stroke patients with spatial neglect in two cancellation tasks across different modalities (paper-and-pencil vs. digital) and display sizes (small, medium, large). We found that the CoC measure did neither vary considerably between paper-and-pencil versus digital versions, nor between different digital size formats. The CoC derived from cancellation tasks thus seems robust to test digitization. A further aim of the present study was to evaluate three additional parameters of search behavior which became available through digitization. We observed slower search behavior, increased distance between two consecutively identified items, and signs of a more strategic search for neglect patients than control patients without neglect. Machine learning classifications indicated that – beyond the CoC measure – the latter three variables can help to differentiate stroke patients with spatial neglect from thosewithout.
PATAN-domain response regulators interact with the Type IV pilus motor to control phototactic orientation in the cyanobacterium Synechocystis sp. PCC 6803
Authors: Han Yu , Jakob Annik , Engel Sophia , Wilde Annegret , Schuergers Nils 
Published: June 2021

AbstractMany prokaryotes show complex behaviors that require the intricate spatial and temporal organization of cellular protein machineries, leading to asymmetrical protein distribution and cell polarity. One such behavior is cyanobacterial phototaxis which relies on the dynamic localization of the Type IV pilus motor proteins in response to light. In the cyanobacterium Synechocystis, various signaling systems encompassing chemotaxis-related CheY- and PatA-like response regulators are critical players in switching between positive and negative phototaxis depending on the light intensity and wavelength. In this study, we show that PatA-type regulators evolved from chemosensory systems. Using fluorescence microscopy and yeast-two-hybrid analysis, we demonstrate that they localize to the inner membrane, where they interact with the N-terminal cytoplasmic domain of PilC and the pilus assembly ATPase PilB1. By separately expressing the subdomains of the response regulator PixE, we confirm that only the N-terminal PATAN domain interacts with PilB1, localizes to the membrane, and is sufficient to reverse phototactic orientation. These experiments established that the PATAN domain is the principal output domain of PatA-type regulators which we presume to modulate pilus extension by binding to the pilus motor components.
Bamboos flower after the return of almost the same sun-moon phasing as at seedling emergence
Authors: Clerget Benoit 
Published: June 2021

AbstractAll Asian woody bamboo species of economic importance are semelparous. They remain vegetative during time intervals that are specific to each species and range from three to 120 years, with notable concentrations around a series of values (3, 7-8, 14-17, 29-36, 42-48, 61-64, and 120 years). Then, they flower gregariously within a short period. Entire forests temporarily disappear during these periods, and the dates of these dramatic events have been recorded over the last 200 years.While searching for a correlated environmental cue, I have found that the concentrations of flowering cycles were highly correlated with the series of successive returns of almost the same sun-moon phasing as at seedling emergence. On basis of knowledge on plant photoperiod sensitivity, I hypothesize that bamboo plants i) run a lunar cellular clock that is set at the full moon, ii) retain in their cellular memory the exact sun-moon phasing of the year of their emergence as seedlings, and iii) inhibit flowering until the occurrence of a unique, species-specific sun-moon phasing that is shifted by a precise amount from the sun-moon phasing at their emergence. Recent evidence of plant responses to lunar cycles supports this hypothesis, for which experimental evidence is now anticipated.HighlightThe long-standing enigma of the triggering of the gregarious flowering of bamboos is possibly solved. Flowering would be inhibited until the occurrence of the species-specific sun-moon phasing.