Drug Development.

Background: Accumulation of misfolded a-synuclein protein in intracellular inclusion bodies of dopaminergic neurons underlies the pathogenesis of synucleinopathies, which include Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). Therefore, clearance of misfolded α-synuclein from dopaminergic neurons could in principle offer a an approach for modifying synucleinopathies, which currently remain untreatable.

Method: In this study, we employ the Affinity-directed PROtein Missile (AdPROM) system consisting of the substrate receptor of the CUL2-E3 ligase complex VHL and a nanobody selectively recognising the human α-synuclein protein RESULT: We demonstrate targeted degradation of endogenous α-synuclein from human cell lines with exquisite selectivity.

Validation of cross-progeny variance genomic prediction using simulations and experimental data in winter elite bread wheat.

From simulations and experimental data, the quality of cross progeny variance genomic predictions may be high, but depends on trait architecture and necessitates sufficient number of progenies. Genomic predictions are used to select genitors and crosses in plant breeding. The usefulness criterion (UC) is a cross-selection criterion that necessitates the estimation of parental mean (PM) and progeny standard deviation (SD).

Comparison of genomic-enabled cross selection criteria for the improvement of inbred line breeding populations.

A crucial step in inbred plant breeding is the choice of mating design to derive high-performing inbred varieties while also maintaining a competitive breeding population to secure sufficient genetic gain in future generations. In practice, the mating design usually relies on crosses involving the best parental inbred lines to ensure high mean progeny performance. This excludes crosses involving lower performing but more complementary parents in terms of favorable alleles.

Serum albumin binding knob domains engineered within a V framework III bispecific antibody format and as chimeric peptides.

Background: Serum albumin binding is an established mechanism to extend the serum half-life of antibody fragments and peptides. The cysteine rich knob domains, isolated from bovine antibody ultralong CDRH3, are the smallest single chain antibody fragments described to date and versatile tools for protein engineering.

Methods: Here, we used phage display of bovine immune material to derive knob domains against human and rodent serum albumins.

A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling.

Metabolic rewiring is often considered an adaptive pressure limiting metastasis formation; however, some nutrients available at distant organs may inherently promote metastatic growth. We find that the lung and liver are lipid-rich environments. Moreover, we observe that pre-metastatic niche formation increases palmitate availability only in the lung, whereas a high-fat diet increases it in both organs.