Multifaceted roles of Fcγ receptors in COVID-19 and vaccine responses.

Recent data have revealed various effector functions of FcγRs in immune responses against challenges with SARS-CoV-2 virus. FcγRs act as a bridge between antibody specificity and effector cells. In many cases, IgG/FcγR interactions generate cell-mediated immune protection from infection via ADCP or ADCC. These responses are beneficial, as they may participate in virus elimination and persist longer than neutralizing anti-Spike antibodies. In contrast, these interactions may sometimes prove beneficial to the virus by enhancing viral uptake into phagocytic cells via ADE and causing excessive inflammation. Here, we summarize key features of FcγRs, discuss effector functions, clinical relevance, and factors influencing FcγR-mediated immune responses in COVID-19 and vaccine responses, and consider IVIg and kinase inhibitors for targeting FcγRs signaling in COVID-19.

Challenges and solutions in COVID-19 related pandemic solid waste management (PSWM) - A detailed analysis with special focus on plastic waste

A pandemic like novel coronavirus 2’ (SARS-CoV-2) not only poses serious public health repercussions but also affects the socio-economic and environmental conditions of the affected countries. The increased consumption of material resources in conjunction with ‘containment and preventive measures’ is generating an unprecedented amount of potentially infectious solid waste, especially that of plastic origin, which if mismanaged, is bound to affect the ecosystem and public health, as the virus can survive on fomites for longer duration. COVID-19 related pandemic waste, such as Personal protective equipment (PPEs), sanitizer and water bottles, disinfection wipes, and Single use Plastics (SUPs) products has already found its way to the aquatic and terrestrial environment. Even before the start of the COVID-19 pandemic, the management of plastic waste, an environmental stressor with trans-boundary migration capabilities, was a major environmental issue for every stake-holder.In this paper, we propose a separate domain in the waste management framework for the effective management of pandemic related solid waste. Factors and sources contributing to increased plastic waste generation are discussed in detail. A concise picture of global plastic demand through sectors and polymer types is presented and speculations are made on how COVID-19 is going to affect the plastic demand. Current solid waste handling and management practices in developed and developing countries are critically examined from the perspective of this pandemic. We identified various challenges that waste management sectors are facing currently and offered possible solutions.Concerns of transmission through fomites is bringing a change in public behavior and consumption pattern which affects 3R practices, while fear of secondary transmission from occupational infections is interfering with 3R practices at end-of-life plastic waste management. The legislative and restrictive frameworks on plastic use being currently put-on hold at the governmental level to ensure public safety are being used by the plastic industry to lobby for increased plastic consumption. The inability of the governments to win public confidence is further escalating unsustainable practices and slowing the shift towards sustainable economy. It is imperative to enforce sustainable practices without putting public safety at risk and to ensure that an unsustainable societal attitude wouldn’t be reinstated in the post-pandemic world. Lastly, eight research and policy points suggested here may guide future studies and governmental frameworks in the domain of COVID-19 pandemic related solid waste handling and management.

Do we still need animals? Surveying the role of animal-free models in Alzheimer's and Parkinson's disease research.

The use of animals in neuroscience and biomedical research remains controversial. Policy is built around the "3R" principle of "Refining, Reducing and Replacing" animal experiments, and across the globe, different initiatives stimulate the use of animal-free methods. Based on an extensive literature screen to map the development and adoption of animal-free methods in Alzheimer's and Parkinson's disease research, we find that at least two in three examined studies rely on animals or on animal-derived models. Among the animal-free studies, the relative contribution of innovative models that may replace animal experiments is limited. We argue that the distinction between animal research and alternative models presents a false dichotomy, as the role and scientific value of both animal and animal-free approaches are intertwined. Calls to halt all animal experiments appear premature, as insufficient non-animal-based alternatives are available and their development lags behind. In light of this, we highlight the need for objective, unprejudiced monitoring, and more robust performance indicators of animal-free approaches.

The Mitochondrial Outer Membrane Protein Tom70-Mediator in Protein Traffic, Membrane Contact Sites and Innate Immunity.

Tom70 is a versatile adaptor protein of 70 kDa anchored in the outer membrane of mitochondria in metazoa, fungi and amoeba. The tertiary structure was resolved for the Tom70 of yeast, showing 26 α-helices, most of them participating in the formation of 11 tetratricopeptide repeat (TPR) motifs. Tom70 serves as a docking site for cytosolic chaperone proteins and co-chaperones and is thereby involved in the uptake of newly synthesized chaperone-bound proteins in mitochondrial biogenesis. In yeast, Tom70 additionally mediates ER-mitochondria contacts via binding to sterol transporter Lam6/Ltc1. In mammalian cells, TOM70 promotes endoplasmic reticulum (ER) to mitochondria Ca2+ transfer by association with the inositol-1,4,5-triphosphate receptor type 3 (IP3R3). TOM70 is specifically targeted by the Bcl-2-related protein MCL-1 that acts as an anti-apoptotic protein in macrophages infected by intracellular pathogens, but also in many cancer cells. By participating in the recruitment of PINK1 and the E3 ubiquitin ligase Parkin, TOM70 can be implicated in the development of Parkinson's disease. TOM70 acts as receptor of the mitochondrial antiviral-signaling protein (MAVS) and thereby participates in the corresponding system of innate immunity against viral infections. The protein encoded by Orf9b in the genome of SARS-CoV-2 binds to TOM70, probably compromising the synthesis of type I interferons.

Public perception of laboratory animal testing: Historical, philosophical, and ethical view.

The use of laboratory animals in biomedical research is a matter of intense public debate. Recent statistics indicates that about half of the western population, sensitive to this discussion, would be in favor of animal testing while the other half would oppose it. Here, outlining scientific, historical, ethical, and philosophical aspects, we provide an integrated view explaining the reasons why biomedical research can hardly abandon laboratory animal testing. In this paper, we retrace the historical moments that mark the relationship between humans and other animal species. Then starting from Darwin's position on animal experimentation, we outline the steps that over time allowed the introduction of laws and rules that regulate animals' use in biomedical research. In our analysis, we present the perspectives of various authors, with the aim of delineating a theoretical framework within which to insert the ethical debate on laboratory animals research. Through the analysis of fundamental philosophical concepts and some practical examples, we propose a view according to which laboratory animals experimentation become ethically acceptable as far as it is guided by the goal of improving humans and other animal species (i.e., pets) life. Among the elements analyzed, there is the concept of responsibility that only active moral subjects (humans) have towards themselves and towards passive moral subjects (other animal species). We delineate the principle of cruelty that is useful to understand why research in laboratory animals should not be assimilated to a cruel act. Moreover, we touch upon the concepts of necessity and "good cause" to underline that, if biomedical research would have the possibility to avoid using animals, it would surely do that. To provide an example of the negative consequences occurring from not allowing laboratory animal research, we analyze the recent experience of Covid-19 epidemic. Finally, recalling the principle of "heuristics and biases" by Kahneman, we discuss why scientists should reconsider the way they are conveying information about their research to the general public.

Monocyte activation in systemic Covid-19 infection: Assay and rationale.

Mononuclear phagocytes are a widely distributed family of cells contributing to innate and adaptive immunity. Circulating monocytes and tissue macrophages participate in all stages of SARS COVID-19. They contribute to comorbidities predisposing to clinical infection, virus resistance and dissemination, and to host factors that determine disease severity, recovery and sequelae. Assays are available to detect viral infection and antibody responses, but no adequate tests have been developed to measure the activation level of monocytes and tissue macrophages, and the risk of progression to a fatal hyperinflammatory syndrome. Blood monocytes provide a window on the systemic immune response, from production to tissue recruitment, reflecting the impact of infection on the host. Ready availability of blood makes it possible to monitor severity and the risk of potentially lethal complications, by developing tests to assess the status of monocyte activation and its potential for further inflammatory dysregulation after recruitment to tissues and during recovery.