Carbon fixation, in addition to the evolution of metabolism, is a main requirement for the evolution of life. Here, we report a one-pot carbon fixation of acetylene (C2H2) and carbon monoxide (CO) by aqueous nickel sulfide (NiS) under hydrothermal (>100 °C) conditions. A slurry of precipitated NiS converts acetylene and carbon monoxide into a set of C2–4-products that are surprisingly representative for C2–4-segments of all four central CO2-fixation cycles of the domains Bacteria and Archaea, whereby some of the products engage in the same interconversions, as seen in the central CO2-fixation cycles. The results suggest a primordial, chemically predetermined, non-cyclic acetyleno/carboxydotrophic core metabolism. This metabolism is based on aqueous organo–metal chemistry, from which the extant central CO2-fixation cycles based on thioester chemistry would have evolved by piecemeal modifications.
Summary
Adoptive T cell therapy using T-cell receptor (TCR)-engineered T cells allows to redirect T cell specificity and to target any antigen of interest. Here, we apply advanced genetic engineering using clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) for simultaneous editing of TCR α- and β-chains in primary human T cells. Together with non-virally delivered template DNA, this CRISPR-Cas9-system allows for elimination of the endogenous TCR and orthotopic placement of TCR α- and β-chains.
For complete details on the use and execution of this protocol, please refer to
Schober et al. (2019)
and
Müller et al. (2021)
.
Vaccines are the most important means to overcome the SARS–CoV–2 pandemic. They induce specific antibody and T–cell responses but it remains open how well vaccine-induced immunity is preserved over time following homologous and heterologous immunization regimens. Here, we compared the dynamics of humoral and cellular immune responses up to 5 months after homologous or heterologous vaccination with either ChAdOx1–nCoV–19 (ChAd) or BNT162b2 (BNT) or both. Antibody responses significantly waned after vaccination, irrespective of the regimen. The capacity to neutralize SARS-CoV–2 – including variants of concern such as Delta or Omicron – was superior after heterologous compared to homologous BNT vaccination, both of which resulted in longer–lasting humoral immunity than homologous ChAd immunization. T–cell responses showed less waning irrespective of the vaccination regimen. These findings demonstrate that heterologous vaccination with ChAd and BNT is a potent approach to induce long–term humoral and cellular immune protection.
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