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Polymerase chain reaction (PCR)-based assays were widely deployed during the SARS-CoV-2 pandemic for population-scale testing. High-throughput molecular diagnostic laboratories required a high degree of process automation to cope with huge testing demands, fast turnaround times, and quality requirements. However, process developers and optimizers often neglected the critical step of preparing a PCR Master Mix. The construction of PCR Master Mix depends on operator skill during the manual pipetting of reagents. Manual procedures introduce variation, inconsistency, wastage, and potentially risks data integrity. To address this, we developed a liquid-handler-based solution for automated, traceable, and compliant PCR Master Mix preparation. Here, we show that a fully automated PCR Master Mix protocol can replace manual pipetting, even in a diagnostic environment, without affecting accuracy or precision. Ultimately, this method eliminated operator-induced wastage and improved the consistency of the quality of results.

Tuberculosis (TB) is the leading cause of global morbidity and mortality resulting from infectious disease, with over 10.6 million new cases and 1.4 million deaths in 2021. This global emergency is exacerbated by the emergence of multidrug-resistant MDR-TB and extensively drug-resistant XDR-TB; therefore, new drugs and new drug targets are urgently required. From a whole cell phenotypic screen, a series of azetidines derivatives termed BGAz, which elicit potent bactericidal activity with MIC99values <10 μM against drug-sensitive Mycobacterium tuberculosisand MDR-TB, were identified. These compounds demonstrate no detectable drug resistance. The mode of action and target deconvolution studies suggest that these compounds inhibit mycobacterial growth by interfering with cell envelope biogenesis, specifically late-stage mycolic acid biosynthesis. Transcriptomic analysis demonstrates that the BGAz compounds tested display a mode of action distinct from the existing mycobacterial cell wall inhibitors. In addition, the compounds tested exhibit toxicological and PK/PD profiles that pave the way for their development as antitubercular chemotherapies.

Discussion on the impact of microenvironments on macrophage permissiveness to influenza virus infection and to the innate immune responses elicited by such infection.

ABSTRACTIn the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provide a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain of the viral Spike (S) glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic viral infection in a standard 96-h co-incubation assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.

An interview with lesbian writer Debra Anderson is presented. When asked how she felt with winning the 2009 Dayne Ogilvie Award, she says that she is thrilled with receiving the recognition. Anderson relates that she loves to write because it is a way of understanding her purpose in living life as well others' too. She shares that she likes reading and writing about people and situations that are not part of mainstream culture.