bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobility was a Significant Determinant of Reported COVID-19 Incidence During the Omicron Surge in the Most Populous U.S. Counties
Authors: Harris Jeffrey E. 
Published: March 2022

AbstractBackgroundSignificant immune escape by the Omicron variant, along with the emergence of widespread worry fatigue, have called into question the robustness of the previously observed relation between population mobility and COVID-19 incidence.MethodsWe employed principal component analysis to construct a one-dimensional summary indicator of six Google mobility categories. We related this mobility indicator to case incidence among 111 of the most populous U.S. counties during the Omicron surge from December 2021 through February 2022.ResultsReported COVID-19 incidence peaked earlier and declined more rapidly among those counties exhibiting more extensive decline in mobility between December 20 and January 3. Based upon a fixed-effects, longitudinal cohort model, we estimated that every 1-percent decline in mobility between December 20 and January 3 was associated with a 0.63 percent decline in peak incidence during the week ending January 17 (95% confidence interval, 0.40-0.86 percent). Based upon a cross-sectional analysis including mean household size and vaccination participation as covariates, we estimated that the same 1-percent decline in mobility was associated with a 0.36 percent decline in cumulative reported COVID-19 incidence from January 10 through February 28 (95% CI, 0.18-0.54 percent).ConclusionOmicron did not simply sweep through the U.S. population until it ran out of susceptible individuals to infect. To the contrary, a significant fraction managed to avoid infection by engaging in risk-mitigating behaviors. More broadly, the behavioral response to perceived risk should be viewed as an intrinsic component of the natural course of epidemics in humans.
IRON REGULATORY PROTEIN (IRP)-MEDIATED IRON HOMEOSTASIS IS CRITICAL FOR NEUTROPHIL DEVELOPMENT AND DIFFERENTIATION IN THE BONE MARROW
Authors: Bonadonna Michael , Altamura Sandro , Tybl Elisabeth , Palais Gael , Qatato Maria , Polycarpou-Schwarz Maria , Schneider Martin , Kalk Christina , Rüdiger Wibke , Ertl Alina , Anstee Natasha , Bogeska Ruzhica , Helm Dominic , Milsom Michael D. , Galy Bruno 
Published: March 2022

ABSTRACTIron is mostly devoted to the hemoglobinization of erythrocytes for oxygen transport. Yet, emerging evidence points to a broader role for the metal in hematopoiesis, including the formation of the immune system. Iron availability in mammalian cells is controlled by iron-regulatory proteins (IRP)-1 and −2. We report that global disruption of both IRP1 and IRP2 in adult mice impairs neutrophil development and differentiation in the bone marrow, yielding immature neutrophils with abnormally high glycolytic and autophagic activity, resulting in neutropenia. IRPs promote neutrophil differentiation in a cell intrinsic manner by securing cellular iron supply together with transcriptional control of neutropoiesis to facilitate differentiation to fully mature neutrophils. Unlike neutrophils, monocyte count was not affected by IRP and iron deficiency, suggesting a lineage-specific effect of iron on myeloid output. This study unveils the previously unrecognized importance of IRPs and iron metabolism in the formation of a major branch of the innate immune system.
Thermoregulatory Dynamics Reveal Sex-Specific Inflammatory Responses to Experimental Autoimmune Encephalomyelitis in Mice: Implications for Multiple Sclerosis-Induced Fatigue in Females
Authors: Faraji Jamshid , Bettenson Dennis , Babatunde Stella , Gangur-Powell Tabitha , Yong Voon Wee , Metz Gerlinde A.S. 
Published: March 2022

AbstractThe course of multiple sclerosis (MS) is characterized by striking sex differences in symptoms such as fatigue and impaired thermal regulation, which are associated with aggravated systemic pro-inflammatory processes. The purpose of this study was to replicate these symptoms in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice in the quest to advance the preclinical study of non-motor symptoms of MS. Male and female C57BL/6 mice exposed to a mild form of EAE were evaluated for the progression of clinical, behavioural, thermal, and inflammatory processes. We show higher susceptibility in females to EAE than males based on greater clinical score and cumulative disease index (CDI), fatigue-like and anxiety-like behaviours. Accordingly, infrared (IR) thermography indicated higher cutaneous temperature in females from post-induction days 12 to 23. Females also responded to EAE with greater splenic and adrenal gland weights than males as well as sex-specific changes in pro- and anti-inflammatory cytokines. These findings provide the first evidence of a sex-specific thermal response to immune-mediated demyelination, thus proposing a non-invasive assessment approach of the psychophysiological dynamics in EAE mice. The results are discussed in relation to the thermoregulatory correlates of fatigue and how endogenously elevated body temperature without direct heat exposure may be linked to psychomotor inhibition in patients with MS.
Observation of topological action potentials in engineered tissues
Authors: Ori Hillel , Ramirez Marc Duque , Hayward Rebecca Frank , Tian He , Ortiz Gloria , Cohen Adam E. 
Published: March 2022

AbstractDue to the nonlinear current-voltage relations of ion channels, an interface between two tissues can have very different bioelectrical properties compared to either tissue on its own. Here we show experimentally that gap junction-coupled interfaces between non-excitable tissues can be electrically excitable. This topologically protected excitability occurs over a far larger range of ion channel expression levels than does excitability in the bulk. Topological excitations at tissue interfaces can cause local elevations in calcium concentration, possibly providing a bioelectrical mechanism for interface sensing. As in condensed matter physics, topological excitations in electrophysiology constitute a distinct class of phenomena which may show exotic and novel properties.
Patterns of retrieval-related cortico-striatal connectivity are stable across the adult lifespan
Authors: Hill Paul F. , de Chastelaine Marianne , Rugg Michael D. 
Published: March 2022

AbstractMemory retrieval effects in the striatum are well documented and robust across a number of experimental paradigms and stimulus materials. However, the functional significance of these effects, and whether they are moderated by age, remains unclear. In the present study, we used fMRI paired with an associative recognition task to examine retrieval effects in the striatum in a large sample of healthy young, middle aged, and older adults. We identified anatomically segregated patterns of enhanced striatal BOLD activity during recollection- and familiarity-based memory judgments. Successful recollection was associated with enhanced BOLD activity in bilateral putamen and nucleus accumbens. Familiarity effects were evident in the head of the caudate nucleus bilaterally. Crucially, none of these effects were reliably moderated by age. Using psychophysiological interaction analyses, we observed a monitoring-related increase in functional connectivity between the caudate and regions of the frontoparietal control network, and between the putamen and bilateral retrosplenial cortex and intraparietal sulcus. In all instances, monitoring-related increases in cortico-striatal connectivity were unmoderated by age. These results suggest that the striatum, and the caudate in particular, couples with the frontoparietal control network to support top-down retrieval monitoring operations, and that the integrity of these effects are preserved in advanced age.
VEGFR3 modulates brain microvessel branching in a mouse model of 22q11.2 deletion syndrome
Authors: Cioffi Sara , Flore Gemma , Martucciello Stefania , Bilio Marchesa , Turturo Maria Giuseppina , Illingworth Elizabeth 
Published: March 2022

ABSTRACTThe loss of a single copy of TBX1 accounts for most of the clinical signs and symptoms of 22q11.2 deletion syndrome (22q11.2DS), a common genetic disorder that is characterized by multiple congenital anomalies and brain-related clinical problems, some of which likely have vascular origins. Tbx1 mutant mice have brain vascular anomalies, thus making them a useful model to gain insights into the brain disorders associated with the human disease. Here, we found that Tbx1 has a dynamic expression pattern in brain endothelial cells (ECs), including tip cells, during early vascularization, but it is not expressed in EC progenitors. Its main morphogenetic function in the brain is to regulate negatively filopodia biogenesis and vessel branching. Because of similar phenotypes reported for Vegfr3 loss of function, we pursued a mouse genetic approach to test TBX1-VEGFR3 interaction through gain and loss of function experiments. Vegfr3 is expressed in brain ECs with extensive overlap with Tbx1 expression. We demonstrate that inactivating Vegfr3 in the Tbx1 expression domain in a Tbx1 mutant background enhances vessel branching and filopodia formation to a greater extent than that observed in the individual mutants. Furthermore, using a mouse transgenic line, we show that increasing Vegfr3 expression in the Tbx1 expression domain fully rescued the vessel branching and filopodia phenotypes caused by Tbx1 loss of function. Similar results were obtained using an in vitro model of endothelial tubulogenesis. Overall, these results provide genetic evidence that Vegfr3 is a regulator of early vessel branching and filopodia formation in the brain, and is a likely critical effector of the brain vascular phenotype caused by Tbx1 loss of function.
Geometry of spiking patterns in early visual cortex: a Topological Data Analytic approach
Authors: Guidolin Andrea , Desroches Mathieu , Victor Jonathan D. , Purpura Keith P. , Rodrigues Serafim 
Published: March 2022

AbstractIn the brain, spiking patterns live in a high-dimensional space of neurons and time. Thus, determining the intrinsic structure of this space presents a theoretical and experimental challenge. To address this challenge, we introduce a new framework for applying topological data analysis (TDA) to spike train data and use it to determine the geometry of spiking patterns in the visual cortex. Key to our approach is a parameterized family of distances based on the timing of spikes that quantifies the dissimilarity between neuronal responses. We applied TDA to visually driven single-unit and multiple single-unit spiking activity in macaque V1 and V2. TDA across timescales reveals a common geometry for spiking patterns in V1 and V2 which, among simple models, is most similar to that of a low-dimensional space endowed with Euclidean or hyperbolic geometry with modest curvature. Remarkably, the inferred geometry depends on timescale, and is clearest for the timescales that are important for encoding contrast, orientation, and spatial correlations.
Higher visual areas act like domain-general filters with strong selectivity and functional specialization
Authors: Khosla Meenakshi , Wehbe Leila 
Published: March 2022

AbstractNeuroscientific studies rely heavily on a-priori hypotheses, which can bias results toward existing theories. Here, we use a hypothesis-neutral approach to study category selectivity in higher visual cortex. Using only stimulus images and their associated fMRI activity, we constrain randomly initialized neural networks to predict voxel activity. Despite no category-level supervision, the units in the trained networks act as detectors for semantic concepts like ‘faces’ or ‘words’, providing solid empirical support for categorical selectivity. Importantly, this selectivity is maintained when training the networks without images that contain the preferred category, strongly suggesting that selectivity is not domain-specific machinery, but sensitivity to generic patterns that characterize preferred categories. The ability of the models’ representations to transfer to perceptual tasks further reveals the functional role of their selective responses. Finally, our models show selectivity only for a limited number of categories, all previously identified, suggesting that the essential categories are already known.TeaserModels trained solely to predict fMRI activity from images reveal strong category selectivity in higher visual areas, even without exposure to these categories in training.
Minicollagens play the governing role in polar capsule formation in parasitic cnidarians, the Myxozoa
Authors: Kyslík Jiří , Vancová Marie , Bartošová-Sojková Pavla , Lövy Alena , Holzer Astrid S. , Fiala Ivan 
Published: March 2022

AbstractMinicollagens are major structural components in the biogenesis of nematocysts in Cnidaria. Sequence mining and recent proteomic analysis of polar capsules, homologues of cnidarian nematocysts, have confirmed the presence of minicollagens in this evolutionarily ancient cnidarian endoparasitic group. Nonetheless, the role of nematocyst-associated proteins in polar capsule morphogenesis has never been studied in myxozoans. Here, we report the gene expression of three myxozoan minicollagens, ncol-1, ncol-3, and the recently identified ncol-5, during the intrapiscine development of Myxidium lieberkuehni, the myxozoan parasite of Northern pike Esox lucius. Moreover, we determined the abundance and localisation of Ncol-1 and Ncol-5 proteins in the developing myxozoan stages by western blotting and by immunofluorescence and immunogold electron microscopy. We found that expression of minicollagens was spatiotemporally restricted to developing polar capsules in sporogonic stages. Intriguingly, Ncol-1 and Ncol-5 were localised as major components of the polar capsule wall and polar tubule. These results support the common origin of nematocysts and myxozoan polar capsules. Furthermore, our findings have practical implications for a more accurate identification of developmental stages of myxozoan parasites.
Resolving the mesoscopic missing link: Biophysical modeling of EEG from cortical columns in primates
Authors: Herrera Beatriz , Westerberg Jacob A. , Schall Michelle S. , Maier Alexander , Woodman Geoffrey F. , Schall Jeffrey D. , Riera Jorge J. 
Published: March 2022

AbstractEvent-related potentials (ERP) are among the most widely measured indices for studying human cognition. While their timing and magnitude provide valuable insights, their usefulness is limited by our understanding of their neural generators at the circuit level. Inverse source localization offers insights into such generators, but their solutions are not unique. To address this problem, scientists have assumed the source space generating such signals comprises a set of discrete equivalent current dipoles, representing the activity of small cortical regions. Based on this notion, theoretical studies have employed forward modeling of scalp potentials to understand how changes in circuit-level dynamics translate into macroscopic ERPs. However, experimental validation is lacking because it requires in vivo measurements of intracranial brain sources. Laminar local field potentials (LFP) offer a mechanism for estimating intracranial current sources. Yet, a theoretical link between LFPs and intracranial brain sources is missing. Here, we present a forward modeling approach for estimating mesoscopic intracranial brain sources from LFPs and predict their contribution to macroscopic ERPs. We evaluate the accuracy of this LFP-based representation of brain sources utilizing synthetic laminar neurophysiological measurements and then demonstrate the power of the approach in vivo to clarify the source of a representative cognitive ERP component. To that end, LFP was measured across the cortical layers of visual area V4 in macaque monkeys performing an attention demanding task. We show that area V4 generates dipoles through layer-specific transsynaptic currents that biophysically recapitulate the ERP component through the detailed forward modeling. The constraints imposed on EEG production by this method also revealed an important dissociation between computational and biophysical contributors. As such, this approach represents an important bridge from the mesoscopic activity of cortical columns to the patterns of EEG we measure at the scalp.HighlightsCognitive EEG production was accurately modeled from empirically measured cortical activity in awake macaques.V4 laminar activity plausibly generates the attention-related signal indexed by the EEG.Models demonstrate the importance of biophysical geometry in cognitive EEG production.
SciCV, the Swiss National Science Foundation’s new CV format
Authors: Strinzel Michaela , Kaltenbrunner Wolfgang , van der Weijden Inge , von Arx Martin , Hill Michael 
Published: March 2022

AbstractBackgroundThe Swiss National Science Foundation (SNSF) tested a new CV format called SciCV to encourage fair, DORA-compliant assessment of grant applicants. It was developed in close collaboration with the academic evaluation community and international experts, introduced through detailed change management and finally tested in its utility by an independent research team of the Center for Science and Technology Studies Leiden (CWTS).MethodsWe present the development of the SciCV pilot and its evaluation by the CWTS research group. The analysis comprised both quantitative and qualitative methods, with (i) surveys and semi-structured interviews with applicants and reviewers, (ii) text analysis of the narrative elements of SciCV, and (iii) participant observation in ten evaluation panel meetings.ResultsNarrative elements and the inclusion of the academic age were rated as most useful new CV elements, while the inclusion of two metrics, the h-index and the relative citation ratio, were received more critically. The omission of a full publication list had similar numbers of supporters and opponents among applicants and reviewers. Less experienced and junior applicants and reviewers rated the new format generally more positively than more senior applicants and reviewers. The text analysis of narrative elements yielded no significant gender specific differences. The participant observation revealed that the new elements in SciCV broadened the information base used in the evaluation of applicants but did not fundamentally alter traditional, publication-centred evaluation practices.ConclusionSciCV was a relevant and successful initiative for the SNSF, which showed that the implementation of a new, well-structured CV format is not only feasible but also something that many stakeholders welcome.The extensive experience and results obtained during the change process formed the basis for the development of SciCV 2.0 at the SNSF. It also offers a basis and guidance for other funding organisations planning similar initiatives.
New features of micro-RNA regulation of mRNA translation and stability revealed by expression of targeted or not targeted reporter genes
Authors: Hudy Dorota , Rzeszowska-Wolny Joanna 
Published: March 2022

ABSTRACTThe existence of translation regulation by RNA-induced silencing complexes (RISCs) composed from Argonaute proteins and micro-RNAs is well established, however the mechanisms underlying specific cellular and miRNA effects and the way in which specific complexes arise are not completely clear.Here we describe experiments withRenillaandFireflyluciferase reporter genes transfected on a PsiCheck2 plasmid into human cancer HCT116 or Me45 cells where only theRenillagene contained or not sequences targeted by micro RNAs (miRNAs) in the 3’UTR. The effects of targeting were miRNA-specific; miRNA-21 caused strong inhibition of translation whereas miRNA-24 or Let-7 caused no change or an increase in global reporterRenillaluciferase synthesis, and the mRNA-protein complexes formed by reporter transcripts in both cell types differed as shown by sucrose gradient sedimentation. In both cell types the presence of miRNA targets onRenillatranscripts affected expression of the co-transfected non-targetedFireflyluciferase, andRenillaandFireflytranscripts were found in the same sucrose gradient fractions. We also observed that specific anti-miRNA oligoribonucleotides influenced expression of theFireflyas well as of theRenillagene, suggesting modulation of non-targeted transcript expression by miRNAs. Our results indicate the existence of interactions between miRNA-regulated and -unregulated transcripts and suggest that the use of the latter as a normalizers in experiments may be biased. We also discuss some hypothetical mechanisms which could explain the observed miRNA-induced effects.
Mesembryanthemum crystallinum plasma membrane root aquaporins are regulated via clathrin-coated vesicles in response to salt stress
Authors: Gómez-Méndez María Fernanda , Vera-Estrella Rosario , Amezcua-Romero Julio César , Rosas-Santiago Paul , Hernández-Domínguez Eric Edmundo , de Luna-Valdez Luis Alberto , Pantoja Omar 
Published: March 2022

ABSTRACTThe regulation of PIP-type aquaporins in the roots of plants has been identified as an important aspect in salinity tolerance. However, the molecular and cellular details underlying this process in halophytes remain unclear. Using free flow electrophoresis and label-free proteomics, we report that the increased abundance of PIPs at the plasma membrane of Mesembryanthemum crystallinum roots under salinity conditions is regulated by clathrin-coated vesicles (CCVs). To understand this regulation, we analyzed several components of the M. crystallinum CCVs complexes: clathrin light chain (McCLC) and subunits μ1 and μ2 of the adaptor complex (McAP1μ and McAP2μ). Co-localization analyses revealed the association between McPIP1;4 and McAP2μ and between McPIP2;1 and McAP1μ, observations corroborated by mbSUS assays, suggesting that aquaporin abundance at the PM is under the control of CCVs. The ability of McPIP1;4 and McPIP2;1 to form homo- and hetero-oligomers was tested and confirmed, as well as their activity as water channels. Also, we found increased phosphorylation of McPIP2;1 only at plasma membrane in response to salt stress. Our results prompt how root PIPs from halophytes are regulated through CCVs trafficking and phosphorylation, impacting their localization, transport activity and abundance under salinity conditions.One-sentence summaryAbundance of plasma membrane aquaporins in M. crystallinum roots increases in response to salinity via a clathrin-coated vesicle-dependent mechanism.