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Vocal communication is used across extant vertebrates, is evolutionarily ancient, and been maintained, in many lineages. Here I review the neural circuit architectures that support intraspecific acoustic signaling in representative anuran, mammalian and avian species as well as two invertebrates, fruit flies and Hawaiian crickets. I focus on hindbrain motor control motifs and their ties to respiratory circuits, expression of receptors for gonadal steroids in motor, sensory, and limbic neurons as well as divergent modalities that evoke vocal responses. Hindbrain and limbic participants in acoustic communication are highly conserved, while forebrain participants have diverged between anurans and mammals, as well as songbirds and rodents. I discuss the roles of natural and sexual selection in driving speciation, as well as exaptation of circuit elements with ancestral roles in respiration, for producing sounds and driving rhythmic vocal features. Recent technical advances in whole brain fMRI across species will enable real time imaging of acoustic signaling partners, tying auditory perception to vocal production.

Abstract Colleges and other organizations are considering testing plans to return to operation as the COVID-19 pandemic continues. Pre-symptomatic spread and high false negative rates for testing may make it difficult to stop viral spread. Here, we develop a stochastic agent-based model of COVID-19 in a university sized population, considering the dynamics of both viral load and false negative rate of tests on the ability of testing to combat viral spread. Reported dynamics of SARS-CoV-2 can lead to an apparent false negative rate from ~ 17 to ~ 48%. Nonuniform distributions of viral load and false negative rate lead to higher requirements for frequency and fraction of population tested in order to bring the apparent Reproduction number (Rt) below 1. Thus, it is important to consider non-uniform dynamics of viral spread and false negative rate in order to model effective testing plans.

Neuromuscular electrical stimulation (NMES) allows activation of muscle fibers in the absence of voluntary force generation. NMES could have the potential to promote muscle homeostasis in the context of muscle disease, but the impacts of NMES on diseased muscle are not well understood. We used the zebrafish Duchenne muscular dystrophy (dmd) mutant and a longitudinal design to elucidate the consequences of NMES on muscle health. We designed four neuromuscular stimulation paradigms loosely based on weightlifting regimens. Each paradigm differentially affected neuromuscular structure, function, and survival. Only endurance neuromuscular stimulation (eNMES) improved all outcome measures. We found that eNMES improves muscle and neuromuscular junction morphology, swimming, and survival. Heme oxygenase and integrin alpha7 are required for eNMES-mediated improvement. Our data indicate that neuromuscular stimulation can be beneficial, suggesting that the right type of activity may benefit patients with muscle disease.

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer in the United States, affecting one million people per year. Patients with aggressive disease have limited treatment options and high mortality, highlighting the need to identify new biomarkers linked to poor clinical outcome. HRAS mutations are found in skin papillomas and cSCCs and increase in frequency when MAP3K family members are inhibited, suggesting a link between blockade of mitogen-activated protein kinase (MAPK) signaling and initiation of RAS-primed cells. Tpl2, a MAP3K gene, can serve as a tumor suppressor gene in cSCC. We have previously shown that upon Tpl2 ablation, mice have heightened sensitivity to aberrant RAS signaling. Tpl2-/- mice display significantly higher numbers of papillomas and cSCCs in two-stage chemical carcinogenesis studies and increased tumorigenicity of keratinocytes expressing oncogenic v-rasHa in nude mouse skin grafts. In part, this is mediated through increased mesenchymal-epithelial transition factor (MET) receptor activity. Epidermal Growth Factor Receptor (EGFR) is reported to be an essential factor for MET-driven carcinogenesis and MET activation may confer resistance to EGFR therapies, suggesting that the concurrent use of both an EGFR inhibitor and a MET inhibitor may show promise in advanced cSCCs. In this study we assessed whether normal or Ras-transformed Tpl2-/- keratinocytes have aberrant EGFR signaling and whether concomitant treatment with EGFR/MET tyrosine kinase inhibitors was more effective than single agents in reducing growth and angiogenic potential of Ras-transformed keratinocytes. Tpl2-/- keratinocytes exhibited increased HER-2 and STAT-3 under basal conditions and elevated p-MET and p-EGFR when transduced with oncogenic RAS. Inhibition of MET by Capmatinib increased p-EGFR in Tpl2-/- keratinocytes and papillomas, and inhibition of EGFR by Gefitinib increased HER2 and HER3 signaling in both genotypes. Treatment of keratinocytes with EGFR and MET inhibitors, in combination, significantly enhanced endothelial tube formation, MMP-9 activity and activation of other RTKs, with more pronounced effects when Tpl2 was ablated. These data indicate that Tpl2 cross-talks with both EGFR and MET signaling pathways. Upon inhibition of EGFR/MET signaling, a myriad of escape mechanisms exists in keratinocytes to overcome targeted drug effects.

Abstract Background Secondary dystroglycanopathies are muscular dystrophies that result from mutations in genes that participate in Dystroglycan glycosylation. Glycosylation of Dystroglycan is essential for muscle fibers to adhere to the muscle extracellular matrix (myomatrix). Although the myomatrix is disrupted in a number of secondary dystroglycanopathies, it is unknown whether improving the myomatrix is beneficial for these conditions. We previously determined that either NAD+ supplementation or overexpression of Paxillin are sufficient to improve muscle structure and the myomatrix in a zebrafish model of primary dystroglycanopathy. Here, we investigate how these modulations affect neuromuscular phenotypes in zebrafish fukutin-related protein (fkrp) morphants modeling FKRP-associated secondary dystroglycanopathy. Results We found that NAD+ supplementation prior to muscle development improved muscle structure, myotendinous junction structure, and muscle function in fkrp morphants. However, Paxillin overexpression did not improve any of these parameters in fkrp morphants. As movement also requires neuromuscular junction formation, we examined early neuromuscular junction development in fkrp morphants. The length of neuromuscular junctions was disrupted in fkrp morphants. NAD+ supplementation prior to neuromuscular junction development improved length. We investigated NMJ formation in dystroglycan (dag1) morphants and found that although NMJ morphology is disrupted in dag1 morphants, NAD+ is not sufficient to improve NMJ morphology in dag1 morphants. Ubiquitous overexpression of Fkrp rescued the fkrp morphant phenotype but muscle-specific overexpression only improved myotendinous junction structure. Conclusions These data indicate that Fkrp plays an early and essential role in muscle, myotendinous junction, and neuromuscular junction development. These data also indicate that, at least in the zebrafish model, FKRP-associated dystroglycanopathy does not exactly phenocopy DG-deficiency. Paxillin overexpression improves muscle structure in dag1 morphants but not fkrp morphants. In contrast, NAD+ supplementation improves NMJ morphology in fkrp morphants but not dag1 morphants. Finally, these data show that muscle-specific expression of Fkrp is insufficient to rescue muscle development and homeostasis.

The host innate immune system has developed elegant processes for the detection and clearance of invasive fungal pathogens. These strategies may also aid in the spread of pathogens in vivo, although technical limitations have previously hindered our ability to view the host innate immune and endothelial cells to probe their roles in spreading disease. Here, we have leveraged zebrafish larvae as a model to view the interactions of these host processes with the fungal pathogen Candida albicans in vivo. We examined three potential host-mediated mechanisms of fungal spread: movement inside phagocytes in a "Trojan Horse" mechanism, inflammation-assisted spread, and endothelial barrier passage. Utilizing both chemical and genetic tools, we systematically tested the loss of neutrophils and macrophages and the loss of blood flow on yeast cell spread. Both neutrophils and macrophages respond to yeast-locked and wild type C. albicans in our model and time-lapse imaging revealed that macrophages can support yeast spread in a "Trojan Horse" mechanism. Surprisingly, loss of immune cells or inflammation does not alter dissemination dynamics. On the other hand, when blood flow is blocked, yeast can cross into blood vessels but they are limited in how far they travel. Blockade of both phagocytes and circulation reduces rates of dissemination and significantly limits the distance of fungal spread from the infection site. Together, this data suggests a redundant two-step process whereby (1) yeast cross the endothelium inside phagocytes or via direct uptake, and then (2) they utilize blood flow or phagocytes to travel to distant sites.

Abstract We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and $$90\%$$ 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5–$$20~\mathrm {deg}^2$$ 20deg2 requires at least three detectors of sensitivity within a factor of $$\sim 2$$ ∼2 of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.

This study examined administrator and faculty perceptions of the frequency and pervasiveness of student academic dishonesty, including their perceptions of the personal and contextual factors that affect whether a student is likely to engage in any form of academic dishonesty. One important contextual factor examined in this study was the extent to which the respondents thought that using the Internet in a course, delivering a course via distance education, or the availability of digital text through the Internet impacted the prevalence, prevention, and detection of academic dishonesty.

Listeners locate potential mates using species-specific vocal signals. As tetrapods transitioned from water to land, lungs replaced gills, allowing expiration to drive sound production. Some frogs then returned to water. Here we explore how air-driven sound production changed upon re-entry to preserve essential acoustic information on species identity in the secondarily aquatic frog genus Xenopus. We filmed movements of cartilage and muscles during evoked sound production in isolated larynges. Results refute the current theory for Xenopus vocalization, cavitation, and favor instead sound production by mechanical excitation of laryngeal resonance modes following rapid separation of laryngeal arytenoid discs. Resulting frequency resonance modes (dyads) are intrinsic to the larynx rather than due to neuromuscular control. Dyads are a distinctive acoustic signature. While their component frequencies overlap across species, their ratio is shared within each Xenopus clade providing information on species identity that could facilitate both conspecific localization and ancient species divergence.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Ribonucleoprotein (RNP) granules are higher order assemblies of RNA, RNA-binding proteins, and other proteins, that regulate the transcriptome and protect RNAs from environmental challenge. There is a diverse range of RNP granules, many cytoplasmic, which provide various levels of regulation of RNA metabolism. Here we present evidence that the yeast transcription termination factor, Nab3, is targeted to intranuclear granules in response to glucose starvation by Nab3's proline/glutamine-rich, prion-like domain (PrLD) which can assemble into amyloid in vitro. Localization to the granule is reversible and sensitive to the chemical probe 1,6 hexanediol suggesting condensation is driven by phase separation. Nab3's RNA recognition motif is also required for localization as seen for other PrLD-containing RNA-binding proteins that phase separate. Although the PrLD is necessary, it is not sufficient to localize to the granule. A heterologous PrLD that functionally replaces Nab3's essential PrLD, directed localization to the nuclear granule, however a chimeric Nab3 molecule with a heterologous PrLD that cannot restore termination function or viability, does not form granules. The Nab3 nuclear granule shows properties similar to well characterized cytoplasmic compartments formed by phase separation, suggesting that, as seen for other elements of the transcription machinery, termination factor condensation is functionally important.

Metagenomics is an important method for studying microbial life. However, undergraduate exposure to metagenomics is hindered by associated software, computing demands, and dataset access. In this inquiry-based activity designed for introductory life science majors and nonmajors, students perform an investigation of the bacterial communities inhabiting the human belly button and associated metagenomics data collected through a citizen science project and visualized using an open-access bioinformatics tool. The activity is designed for attainment of the following student learning outcomes: defining terms associated with metagenomics analyses, describing the biological impact of the microbiota on human health, formulating a hypothesis, analyzing and interpreting metagenomics data to compare microbiota, evaluating a specific hypothesis, and synthesizing a conceptual model as to why bacterial populations vary. This activity was implemented in six introductory biology and biotechnology courses across five institutions. Attainment of student learning outcomes was assessed through completion of a quiz and students’ presentations of their findings. In presentations, students demonstrated their ability to develop novel hypotheses and analyze and interpret metagenomic data to evaluate their hypothesis. In quizzes, students demonstrated their ability to define key terms and describe the biological impact of the microbiota on human health. Student learning gains assessment also revealed that students perceived gains for all student learning outcomes. Collectively, our assessment demonstrates achievement of the learning outcomes and supports the utility of this inquiry-based activity to engage undergraduates in the scientific process via analyses of metagenomics datasets and associated exploration of a microbial community that lives on the human body.

African clawed frogs, genus Xenopus, are extraordinary among vertebrates in the diversity of their polyploid species and the high number of independent polyploidization events that occurred during their diversification. Here we update current understanding of the evolutionary history of this group and describe six new species from west and central sub-Saharan Africa, including four tetraploids and two dodecaploids. We provide information on molecular variation, morphology, karyotypes, vocalizations, and estimated geographic ranges, which support the distinctiveness of these new species. We resurrect Xenopus calcaratus from synonymy of Xenopus tropicalis and refer populations from Bioko Island and coastal Cameroon (near Mt. Cameroon) to this species. To facilitate comparisons to the new species, we also provide comments on the type specimens, morphology, and distributions of X. epitropicalis, X. tropicalis, and X. fraseri. This includes significantly restricted application of the names X. fraseri and X. epitropicalis, the first of which we argue is known definitively only from type specimens and possibly one other specimen. Inferring the evolutionary histories of these new species allows refinement of species groups within Xenopus and leads to our recognition of two subgenera (Xenopus and Silurana) and three species groups within the subgenus Xenopus (amieti, laevis, and muelleri species groups).