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This Backstory discusses the development of a SARS-CoV-2 detection method using widely available laboratory equipment. The approach, reported in Cell Reports Methods and STAR Protocols, is intended as a diagnostic tool for COVID-19 that is accessible for resource-limited areas. We describe how the published method and protocols encourage adoption of the detection strategy in different areas and a variety of biological contexts. For complete details on the UnCovid method and protocols, please refer to (Alcántara et al., 2021a; Alcántara et al., 2021b; Mendoza-Rojas, et al., 2021).RNA interference (RNAi) is a technique used for posttranscriptional gene silencing, but lepidopteran insects are not sensitive to RNAi. Here, we present a protocol for knocking down the expression level of target genes by RNAi in Bombyx mori embryos. We describe the preparation of double-stranded RNAs (dsRNAs) of target genes, followed by microinjection of embryos at different developmental stages, with single or mixed dsRNA. Finally, we use RT-qPCR to verify RNAi efficiency. For complete details on the use and execution of this protocol, please refer to Xu et al. (2021).Cryo-electron microscopy (cryo-EM) has produced a number of structural models of the SARS-CoV-2 spike, already prompting biomedical outcomes. However, these reported models and their associated electrostatic potential maps represent an unknown admixture of conformations stemming from the underlying energy landscape of the spike protein. As with any protein, some of the spike's conformational motions are expected to be biophysically relevant, but cannot be interpreted only by static models. Using experimental cryo-EM images, we present the energy landscape of the glycosylated spike protein, and identify the diversity of low-energy conformations in the vicinity of its open (so called 1RBD-up) state. The resulting atomic refinement reveal global and local molecular rearrangements that cannot be inferred from an average 1RBD-up cryo-EM model. Here we report varied degrees of "openness" in global conformations of the 1RBD-up state, not revealed in the single-model interpretations of the density maps, together with conformations that overlap with the reported models. We discover how the glycan shield contributes to the stability of these low-energy conformations. Five out of six binding sites we analyzed, including those for engaging ACE2, therapeutic mini-proteins, linoleic acid, two different kinds of antibodies, switch conformations between their known apo- and holo-conformations, even when the global spike conformation is 1RBD-up. This apo-to-holo switching is reminiscent of a conformational preequilibrium. We found only one binding site, namely that of AB-C135 remains in apo state within all the sampled free energy-minimizing models, suggesting an induced fit mechanism for the docking of this antibody to the spike.This research explores the value proposition of Brazilian non-profits (NPOs) to society, how donors and NPOs perceive value co-creation, and the elements required for value co-creation to occur in a donation context. This study includes case studies with managers and donors from three distinct non-profit organizations in the same sector. We conducted semi-structured interviews, report analysis, and direct observations. The interviews were recorded and typed up for content analysis using the MAXQDA software. The triangulation approach and multilevel data collection contributed to the research's reliability and validity. NPOs propose value through marketing strategies, primarily by humanizing "sales techniques". Donors perceive value co-creation as a beneficial collaborative result. Value co-creation is a way for non-profit organizations to achieve their missions of assisting patients or families in need. Although there is strong evidence of dialogue and transparency elements in the donor-NPO relationship, other factors, such as the individual's background or empathy, stood out more in this context. Academically, this study contributes to the literature by elucidating the phenomena under multiple actor interaction regimes. Furthermore, most studies on value co-creation focus on customer participation and interaction in private organizational processes (i.e., innovation or feedback), leaving gaps for determining and exploring alternative forms of value co-creation. This gap was filled in this study.This study used critical race theory to examine the changes in awarding of doctoral degrees in Departments of Geography to American citizens who are Black, Latinx, and/or Native American. Data were obtained from the Integrated Postsecondary Education Data System (IPEDS), 1997-2019. The data show that of 4918 doctoral degrees awarded from 1997 to 2019, only 86 or 1.64% were awarded to African American students, 122 or 2.39% were awarded to Hispanic American students, and 25 or 0.53% were awarded to Native American students. The differential awarding of degrees was related to the differential funding by race and ethnicity to support their completion of the doctorate degrees. Critical race theory may lead to consciousness for students to review the practice as disparate impact racial discrimination. If policies and practices in departments of geography are not changed there will continue to be few doctoral degrees obtained by Blacks, Hispanics, and Native Americans. The paper offers a model for change.Virus-like particles (VLPs) have significant potential as artificial vaccines and drug delivery systems. The ability to control their size has wide ranging utility but achieving such controlled polymorphism using a single protein subunit is challenging as it requires altering VLP geometry. Here we achieve size control of MS2 bacteriophage VLPs via insertion of amino acid sequences in an external loop to shift morphology to significantly larger forms. The resulting VLP size and geometry is controlled by altering the length and type of the insert. Cryo electron microscopy structures of the new VLPs, in combination with a kinetic model of their assembly, show that the abundance of wild type (T = 3), T = 4, D3 and D5 symmetrical VLPs can be biased in this way. We propose a mechanism whereby the insert leads to a change in the dynamic behavior of the capsid protein dimer, affecting the interconversion between the symmetric and asymmetric conformers and thus determining VLP size and morphology.The S protein subunit 1 (S1) of SARS-CoV-2 is known to be responsible for the binding of the virus to host cell receptors, but the initial intracellular signalling steps following receptor activation of cells in the exocrine pancreas are unknown. Using an intact live mouse pancreatic lobule preparation, we observed that S1 elicited Ca2+ signals in stellate cells and macrophages, but not in the dominant acinar cells. The Ca2+ signals occurred mostly in the form of repetitive Ca2+ spikes. The probability of observing Ca2+ signals depended on the S1 concentration. The threshold was close to 70 nM, whereas at 600 nM, all cells responded. The SARS-Cov-2 nucleocapsid protein did not elicit any Ca2+ signals in any of the three cell types tested. The S1-induced Ca2+ signals in stellate cells started much faster (122 ± 37s) than those in macrophages (468 ± 68s). Furthermore, the interleukin-18 binding protein (IL-18BP) abolished the responses in macrophages without affecting the Ca2+ signals in stellate cells. The S1-elicited Ca2+ signals were completely dependent on the presence of external Ca2+ and were abolished by a selective inhibitor (CM4620) of Orai1 Ca2+ Release Activated Ca2+ channels. click here SARS-CoV-2 may contribute to acute pancreatitis, an often fatal inflammatory human disease. The S1-elicited Ca2+ signals we have observed in the pancreatic stellate cells and endogenous macrophages may play an important part in the development of the inflammatory process.Acute respiratory distress syndrome (ARDS) caused by coronavirus disease (COVID-19) is a serious complication that requires early recognition. Autopsy reports or biopsies of the lungs in patients with COVID-19 revealed diffuse alveolar damage (DAD) at different stages; the fibrotic phase is usually associated with long-standing severe disease. Care management of hospitalized patients is not easy, given that the risk of incurring a ventilator-induced lung injury (VILI) is high. Additionally, if the patient develops nosocomial infections, sepsis-induced ARDS should be considered in the study of the pathophysiological processes. We present an autopsy case of a hospitalized patient whose death was linked to COVID-19 infection, with the histopathological pattern of advanced pulmonary fibrosis. After prolonged use of non-invasive and invasive ventilation, the patient developed polymicrobial superinfection oh the lungs. After analyzing the individual's clinical history and pulmonary anatomopathological findings, we consider healthcare issues that should lead to an improvement in diagnosis and to more adequate standards of care management among health professionals.Thrombopoietin (TPO)-receptor agonists have heralded a paradigm shift in the treatment of refractory immune thrombocytopenia (ITP). Reactive thrombocytosis has been described as a secondary effect of such therapies. However, the phenomenon of extreme thrombocytosis with morphology mimicking a myeloproliferative neoplasm (MPN) followed by fatal thromboembolism is unusual in this setting. Caution is required in the diagnosis of refractory ITP as well as TPO-receptor agonist dosing in such cases.Understanding the patterns of human mobility between cities has various applications from transport engineering to spatial modeling of the spreading of contagious diseases. We adopt a city-centric, data-driven perspective to quantify such patterns and introduce the mobility signature as a tool for understanding how a city (or a region) is embedded in the wider mobility network. We demonstrate the potential of the mobility signature approach through two applications that build on mobile-phone-based data from Finland. First, we use mobility signatures to show that the well-known radiation model is more accurate for mobility flows associated with larger Finnish cities, while the traditional gravity model appears a better fit for less populated areas. Second, we illustrate how the SARS-CoV-2 pandemic disrupted the mobility patterns in Finland in the spring of 2020. These two cases demonstrate the ability of the mobility signatures to quickly capture features of mobility flows that are harder to extract using more traditional methods.Despite progress toward gender equality in the labor market over the past few decades, gender segregation in labor force composition and labor market outcomes persists. Evidence has shown that job advertisements may express gender preferences, which may selectively attract potential job candidates to apply for a given post and thus reinforce gendered labor force composition and outcomes. Removing gender-explicit words from job advertisements does not fully solve the problem as certain implicit traits are more closely associated with men, such as ambitiousness, while others are more closely associated with women, such as considerateness. However, it is not always possible to find neutral alternatives for these traits, making it hard to search for candidates with desired characteristics without entailing gender discrimination. Existing algorithms mainly focus on the detection of the presence of gender biases in job advertisements without providing a solution to how the text should be (re)worded. To address this problem, we propose an algorithm that evaluates gender bias in the input text and provides guidance on how the text should be debiased by offering alternative wording that is closely related to the original input.