Citizen Science and Open Design: Workshop Findings

An inherent link exists between making things and designing things, often relying on skills, knowledge, and tools, and working together to achieve outcomes. Conventional design and manufac- ture to date has been a closed system requiring professional skills. Traditional manufacture has required a significant initial financial investment for “tooling” to produce large volumes of product (i.e., for “mass production”). In contrast, Digital Manufacture (DM) or Rapid Manufacture (RM) is “the ability to manufacture parts of vir- tually any complexity [and] geometry entirely without the need for tooling.” The latter offers lower financial entry-points and the ability to create bespoke products.1 The following article weaves Open design, Digital Manufacture and Citizen Science together present- ing findings from territory exploring workshops with lay users signposting opportunities and perceived detrimental factors

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The calcium-sensing receptor

Cell surface sensors for extracellular Ca2+ and Mg2+51 provide an important mechanism for the regulation of diverse physiological processes by extracellular divalent mineral ions.53, 190 and 402 These ion sensors function as “calciostats” for Ca2+ and/or Mg2+ that not only regulate divalent mineral metabolism at the level of the whole organism but also control a variety of other cellular processes (e.g., salt and water handing in various epithelia and cell proliferation-differentiation) in terrestrial and aquatic animals, as well as in plants. This chapter will focus on the role of the extracellular calcium-sensing receptor (CaSR) in the mammalian parathyroid, kidney, and other tissues participating in divalent mineral ion homeostasis. The unique properties of the mammalian CaSR include: (1) Having extracellular Ca2+ and Mg2+ as its primary physiological ligands, establishing that ions can function as first messengers. (2) Responding with a millimolar EC50, close to the normal plasma ionized Ca2+ concentration, but several orders of magnitude higher than that for ligands of other G protein–coupled receptors. (3) Possessing a remarkable ability to detect small deviations from the normal ionized calcium concentration of 1.1–1.3 mM, making it an ideal sensor for Ca2+, functioning as a “calciostat.” The identification of inherited disorders due to activating or inactivating mutations of the CaSR, basic research in CaSR biology, the development of CaSR-active compounds (calcimimetics), and the results from clinical trials of calcimimetics have established the biological roles of this receptor in mineral ion homeostasis and have suggested roles of the CaSR in several non-Ca2+ homeostatic processes. The reader is referred to Chapter 65 and other chapters in the section, “Regulation and Disorders of Calcium Homeostasis,” for additional information and background