Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours.

Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.

Structural Analysis of Breast-Milk α-Casein: An α-Helical Conformation Is Required for TLR4-Stimulation.

Breast-milk α-casein is a Toll-like receptor 4 (TLR4) agonist, whereas phosphorylated α-casein does not bind TLR4. The objective of this study was to analyse the structural requirements for these effects. In silico analysis of α-casein indicated high α-helical content with coiled-coil characteristics.

Data-Driven Prediction and Uncertainty Quantification of Process Parameters for Directed Energy Deposition.

Laser-based directed energy deposition using metal powder (DED-LB/M) offers great potential for a flexible production mainly defined by software. To exploit this potential, knowledge of the process parameters required to achieve a specific track geometry is essential. Existing analytical, numerical, and machine-learning approaches, however, are not yet able to predict the process parameters in a satisfactory way.

An insulin hypersecretion phenotype precedes pancreatic β cell failure in MODY3 patient-specific cells.

MODY3 is a monogenic hereditary form of diabetes caused by mutations in the transcription factor HNF1A. The patients progressively develop hyperglycemia due to perturbed insulin secretion, but the pathogenesis is unknown. Using patient-specific hiPSCs, we recapitulate the insulin secretion sensitivity to the membrane depolarizing agent sulfonylurea commonly observed in MODY3 patients.

Visualization and identification of single meteoritic organic molecules by atomic force microscopy.

Using high-resolution atomic force microscopy (AFM) with CO-functionalized tips, we atomically resolved individual molecules from Murchison meteorite samples. We analyzed powdered Murchison meteorite material directly, as well as processed extracts that we prepared to facilitate characterization by AFM. From the untreated Murchison sample, we resolved very few molecules, as the sample contained mostly small molecules that could not be identified by AFM.