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Markus, P.

Publications and source records attributed to Markus, P..

2 recordsLinked to original sources

Conditions for successful nitrogen removal from source-separated urine by partial nitritation/anammox

Partial nitritation/anammox (PN/A) of source-separated urine is less energy-intensive and potentially cheaper and more environmentally friendly than conventional nitrogen removal from mixed sewage. However, PN/A of undiluted source-separated urine has not yet been established. In this study, the feasibility of PN/A for source-separated urine (total nitrogen {approx} 2 to 3 g-N L-1). To evaluate the influence of different factors, one- and two-stage configurations were operated using different influents, i.e. source-separated urine, synthetic urine, and urine with additional divalent cations. While partial nitritation was successfully achieved in both configurations with digester supernatant and urine, anammox activity was lost shortly after switching from digester supernatant to the urine influents. Toxic organic compounds or pharmaceuticals and the high monovalent to divalent cation ratio were suspected as causes of anammox failure, but were ruled out due to the different reactor configurations and influent compositions tested. Other suspected factors such as COD/N ratio, phosphate and sulfate inhibition, nitrogen compound inhibition, metal inhibition, pH and dissolved oxygen were also systematically excluded. Instead, the high salt concentration in urine compared to the digester supernatant most likely caused the reactor to fail due to the disintegration of large flocs, and the resulting challenge of biomass retention. The shortcomings of the floccular sludge system were overcome by using biofilm carriers, resulting in successful PN/A. This hybrid system ran for 140 days with nitrogen removal rates of up to 1000 mg-N L-1 d-1 with an average of 410 {+/-} 220 mg-N L-1 d-1, and a nitrogen removal efficiency of 93 {+/-} 3% at 30{degrees}C.

bioengineering↗

Progranulin promotes immune evasion of pancreatic adenocarcinoma through regulation of MHCI expression

Immune evasion is indispensable for cancer initiation and progression, although its underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain elusive. Here, we unveiled a cancer cell-autonomous function of PGRN in driving immune evasion in primary PDAC. Tumor- but not macrophage-derived PGRN was associated with poor overall survival in PDAC. Multiplex immunohistochemistry revealed low MHC class I (MHCI) expression and lack of CD8+ T cells infiltration in PGRN-high tumors. Inhibition of PGRN abrogated autophagy-dependent MHCI degradation and restored MHCI expression on PDAC cells. Antibody-based blockade of PGRN in a genetic PDAC mouse model remarkably decelerated tumor initiation and progression. Notably, tumors expressing LCMV-gp33 as model antigen were sensitized towards cytotoxic gp33-TCR transgenic T cells upon anti-PGRN antibody treatment. Overall, our study uncovered an unprecedented role of tumor-derived PGRN in regulating immunogenicity of primary PDAC. STATEMENT OF SIGNIFICANCEImmune evasion is a key property of PDAC, rendering it refractory to immunotherapy. Here we demonstrate that tumor-derived PGRN promotes autophagy-dependent MHCI degradation, while anti-PGRN increases intratumoral CD8 infiltration and blocks tumor progression. With recent advances in T cell-mediated approaches, PGRN represents a pivotal target to enhance tumor antigen-specific cytotoxicity.

cancer biology↗