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Abstract College students lack fact-checking skills, which may lead them to accept information at face value. We report findings from an institution participating in the Digital Polarization Initiative (DPI), a national effort to teach students lateral reading strategies used by expert fact-checkers to verify online information. Lateral reading requires users to leave the information (website) to find out whether someone has already fact-checked the claim, identify the original source, or learn more about the individuals or organizations making the claim. Instructor-matched sections of a general education civics course implemented the DPI curriculum (N = 136 students) or provided business-as-usual civics instruction (N = 94 students). At posttest, students in DPI sections were more likely to use lateral reading to fact-check and correctly evaluate the trustworthiness of information than controls. Aligning with the DPI’s emphasis on using Wikipedia to investigate sources, students in DPI sections reported greater use of Wikipedia at posttest than controls, but did not differ significantly in their trust of Wikipedia. In DPI sections, students who failed to read laterally at posttest reported higher trust of Wikipedia at pretest than students who read at least one problem laterally. Responsiveness to the curriculum was also linked to numbers of online assignments attempted, but unrelated to pretest media literacy knowledge, use of lateral reading, or self-reported use of lateral reading. Further research is needed to determine whether improvements in lateral reading are maintained over time and to explore other factors that might distinguish students whose skills improved after instruction from non-responders.

Abstract Recent studies identified cyclase-associated proteins (CAPs) as important regulators of actin dynamics that control assembly and disassembly of actin filaments (F-actin). While these studies significantly advanced our knowledge of their molecular functions, the physiological relevance of CAPs largely remained elusive. Gene targeting in mice implicated CAP2 in heart physiology and skeletal muscle development. Heart defects in CAP2 mutant mice were associated with altered activity of serum response factor (SRF), a transcription factor involved in multiple biological processes including heart function, but also skeletal muscle development. By exploiting mouse embryonic fibroblasts (MEFs) from CAP2 mutant mice, we aimed at deciphering the CAP2-dependent mechanism relevant for SRF activity. Reporter assays and mRNA quantification by qPCR revealed reduced SRF-dependent gene expression in mutant MEFs. Reduced SRF activity in CAP2 mutant MEFs was associated with altered actin turnover, a shift in the actin equilibrium towards monomeric actin (G-actin) as well as and reduced nuclear levels of myocardin-related transcription factor A (MRTF-A), a transcriptional SRF coactivator that is shuttled out of the nucleus and, hence, inhibited upon G-actin binding. Moreover, pharmacological actin manipulation with jasplakinolide restored MRTF-A distribution in mutant MEFs. Our data are in line with a model in which CAP2 controls the MRTF-SRF pathway in an actin-dependent manner. While MRTF-A localization and SRF activity was impaired under basal conditions, serum stimulation induced nuclear MRTF-A translocation and SRF activity in mutant MEFs similar to controls. In summary, our data revealed that in MEFs CAP2 controls basal MRTF-A localization and SRF activity, while it was dispensable for serum-induced nuclear MRTF-A translocation and SRF stimulation.

Background: The manual muscle test (MMT) is the traditional method to assess the intrinsic hand muscle test. However, this test is qualitative and subjective. A device capable of rapidly measuring motor output along a linear scale may be of value in the evaluation of hand recovery from any neurological impairment. Objective: To demonstrate inter-rater reliability of the Peg Restrained Intrinsic Muscle Evaluator (PRIME) device for measuring intrinsic hand muscle strength in adults with impaired hand functions. Methods: 16 subjects (2 female, 14 male, mean age=47±15 years) with cervical spinal cord injury were enrolled. Intrinsic hand muscle strength of adults were performed by two-tester with use of PRIME device and manual muscle testing, within the same session. Inter-tester correlation was tested by Pearson's correlation and Intraclass correlation coefficient (ICC). Results: Intraclass correlation coefficients for hypothenar, first dorsal interosseous, abductor pollicis brevis and opponence pollicis muscles ranged from 0.7 to 0.8 with hypothenar muscle test being lowest ICC=0.7 and thumb opposition highest, ICC=0.81. Conclusion: Results from this study suggest that PRIME device demonstrates good reliability within testers for quantified measuring of intrinsic hand muscle strength. Further use of PRIME in clinic will aid in diagnostics, medical decision making and evaluation of rehabilitation progress in patients with cervical spinal cord injury.

Interacting self-propelled particles exhibit phase separation or collective motion depending on particle shape. A unified theory connecting these paradigms represents a major challenge in active matter, which the authors address here by modeling active particles as continuum fields.

The coupling of the internal mechanisms of cell polarization to cell shape deformations and subsequent cell crawling poses many interdisciplinary scientific challenges. Several mathematical approaches have been proposed to model the coupling of both processes, where one of the most successful methods relies on a phase field that encodes the morphology of the cell, together with the integration of partial differential equations that account for the polarization mechanism inside the cell domain as defined by the phase field. This approach has been previously employed to model the motion of single cells of the social amoeba Dictyostelium discoideum, a widely used model organism to study actin-driven motility and chemotaxis of eukaryotic cells. Besides single cell motility, Dictyostelium discoideum is also well-known for its collective behavior. Here, we extend the previously introduced model for single cell motility to describe the collective motion of large populations of interacting amoebae by including repulsive interactions between the cells. We performed numerical simulations of this model, first characterizing the motion of single cells in terms of their polarity and velocity vectors. We then systematically studied the collisions between two cells that provided the basic interaction scenarios also observed in larger ensembles of interacting amoebae. Finally, the relevance of the cell density was analyzed, revealing a systematic decrease of the motility with density, associated with the formation of transient cell clusters that emerge in this system even though our model does not include any attractive interactions between cells. This model is a prototypical active matter system for the investigation of the emergent collective dynamics of deformable, self-driven cells with a highly complex, nonlinear coupling of cell shape deformations, self-propulsion and repulsive cell-cell interactions. Understanding these self-organization processes of cells like their autonomous aggregation is of high relevance as collective amoeboid motility is part of wound healing, embryonic morphogenesis or pathological processes like the spreading of metastatic cancer cells.

The actin nucleating and polymerizing formin-like 2 (FMNL2) is upregulated in several cancers and has been shown to play important roles in cell migration, invasion, cell–cell adhesion and filopodia formation. Here, using structured illumination microscopy we show that FMNL2 promotes rapid and highly dynamic filopodia formation in epithelial cells while remaining on the tip of the growing filopodia. This filopodia tip localization depends fully on its N-terminal myristoylation. We further show that FMNL2-dependent filopodia formation requires its serine 1072 phosphorylation within the diaphanous-autoregulatory domain (DAD) by protein kinase C (PKC) α. Consistent with this, filopodia formation depends on PKC activity and PKCα localizes to the base of growing filopodia. Thus, a PKCα–FMNL2 signaling module spatiotemporally controls dynamic filopodia formation.

OBJECTIVES:. We sought to validate prognostic scores in coronavirus disease 2019 including National Early Warning Score, Modified Early Warning Score, and age-based modifications, and define their performance characteristics. DESIGN:. We analyzed prospectively collected data from the Adaptive COVID-19 Treatment Trial. National Early Warning Score was collected daily during the trial, Modified Early Warning Score was calculated, and age applied to both scores. We assessed prognostic value for the end points of recovery, mechanical ventilation, and death for score at enrollment, average, and slope of score over the first 48 hours. SETTING:. A multisite international inpatient trial. PATIENTS:. A total of 1,062 adult nonpregnant inpatients with severe coronavirus disease 2019 pneumonia. INTERVENTIONS:. Adaptive COVID-19 Treatment Trial 1 randomized participants to receive remdesivir or placebo. The prognostic value of predictive scores was evaluated in both groups separately to assess for differential performance in the setting of remdesivir treatment. MEASUREMENTS AND MAIN RESULTS:. For mortality, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.60–0.68), and improved with addition of age (c-index, 0.66–0.74). For recovery, baseline National Early Warning Score and Modified Early Warning Score demonstrated somewhat better prognostic ability (c-index, 0.65–0.69); however, National Early Warning Score+age and Modified Early Warning Score+age further improved performance (c-index, 0.68–0.71). For deterioration, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.59–0.69) and improved with addition of age (c-index, 0.63–0.70). All prognostic performance improvements due to addition of age were significant (p < 0.05). CONCLUSIONS:. In the Adaptive COVID-19 Treatment Trial 1 cohort, National Early Warning Score and Modified Early Warning Score demonstrated moderate prognostic performance in patients with severe coronavirus disease 2019, with improvement in predictive ability for National Early Warning Score+age and Modified Early Warning Score+age. Area under receiver operating curve for National Early Warning Score and Modified Early Warning Score improved in patients receiving remdesivir versus placebo early in the pandemic for recovery and mortality. Although these scores are simple and readily obtainable in myriad settings, in our data set, they were insufficiently predictive to completely replace clinical judgment in coronavirus disease 2019 and may serve best as an adjunct to triage, disposition, and resourcing decisions.

The extracellular cues regulating filamentous actin formation in somatic cell nuclei are unclear. Here, the authors show that activated GPCR signalling initiates transient accumulation of nuclear F-actin/formation in nuclear actin filaments, driven by calcium and requiring the nucleator Formin INF2.

Summary: Cytoskeletal cross talk between actin filaments and microtubules is a common mechanism governing the assembly of cellular structures, i.e., during filopodia formation or cilia organization. However, potential actin-microtubule interactions during mammalian cell divisions are less well understood. At mitotic entry, centrosomes propagate the formation of the mitotic spindle, thereby aligning individual chromosomes to the metaphase plate, a process coined chromosome congression. Here, we identify actin filament assembly spatially defined at centrosomes contemporaneously with spindle microtubules forming during prometaphase. We show that pharmacological Arp2/3 complex inhibition as well as overexpression of the Arp2/3 complex inhibitory protein Arpin decreased spindle actin. As a consequence, mitotic spindle formation is impaired, which resulted in disorganized chromosome congression and ultimately mitotic defects in non-transformed cells. Thus centrosomal Arp2/3 complex activity plays a role in the maintenance of genomic integrity during mitosis. : Biological Sciences; Cell Biology; Organizational Aspects of Cell Biology; Functional Aspects of Cell Biology Subject Areas: Biological Sciences, Cell Biology, Organizational Aspects of Cell Biology, Functional Aspects of Cell Biology

The peritoneal fluid of ovarian carcinoma patients promotes cancer cell invasion and metastatic spread with lysophosphatidic acid (LPA) as a potentially crucial mediator. However, the origin of LPA in ascites and the clinical relevance of individual LPA species have not been addressed. Here, we show that the levels of multiple acyl‐LPA species are strongly elevated in ascites versus plasma and are associated with short relapse‐free survival. Data derived from transcriptome and secretome analyses of primary ascite‐derived cells indicate that (a) the major route of LPA synthesis is the consecutive action of a secretory phospholipase A2 (PLA2) and autotaxin, (b) that the components of this pathway are coordinately upregulated in ascites, and (c) that CD163+CD206+ tumor‐associated macrophages play an essential role as main producers of PLA2G7 and autotaxin. The latter conclusion is consistent with mass spectrometry‐based metabolomic analyses of conditioned medium from ascites cells, which showed that tumor‐associated macrophages, but not tumor cells, are able to produce 20:4 acyl‐LPA in lipid‐free medium. Furthermore, our transcriptomic data revealed that LPA receptor (LPAR) genes are expressed in a clearly cell type‐selective manner: While tumor cells express predominantly LPAR1‐3, macrophages and T cells also express LPAR5 and LPAR6 at high levels, pointing to cell type‐selective LPA signaling pathways. RNA profiling identified cytokines linked to cell motility and migration as the most conspicuous class of LPA‐induced genes in macrophages, suggesting that LPA exerts protumorigenic properties at least in part via the tumor secretome.