Cervical organoids go viral.

In this issue of Cell Stem Cell, Lõhmussaar et al. (2021) describe a versatile platform for generating long-term patient-derived organoids from hysterectomies and Pap brush cells. They establish malignant and benign cervix tissue organoids from both endo- and ectocervix that have applications ranging from precision medicine to infection modeling

Patient-Derived Tumor Organoid Rings for Histologic Characterization and High-Throughput Screening.

Tumor organoids are promising tools for cancer biology investigations and preclinical drug screenings because they are often representative of the histology and drug responses of patients. Here, we introduce a facile protocol to overcome technical limitations by generating patient-derived tumor organoids using a simplified ring-like geometry. This facilitates media exchange and drug treatment for histopathology characterization and automated high-throughput drug screenings. For complete details on the use and execution of this protocol, please refer to Phan et al. (2019)

Solution Structure of Selenoprotein W and NMR Analysis of Its Interaction with 14-3-3 Proteins

Selenium is a trace element with significant biomedical potential. It is essential in mammals due to its occurrence in several proteins in the form of selenocysteine (Sec). One of the most abundant mamma¬lian Sec-containing proteins is selenoprotein W (SelW). This protein of unknown function has a broad expression pattern and contains a candidate CXXU (where U represents Sec) redox motif. Here, we re¬port the solution structure of the Sec13 →Cys variant of mouse SelW determined through high resolution NMR spectroscopy. The protein has a thioredoxin-like fold with the CXXU motif located in an exposed loop similarly to the redox-active site in thioredoxin. Protein dynam¬ics studies revealed the rigidity of the protein backbone and mobility of two external loops and suggested a role of these loops in interaction with SelW partners. Molecular modeling of structures of other mem¬bers of the Rdx family based on the SelW structure identified new con¬served features in these proteins, including an aromatic cluster and in¬teracting loops. Our previous study suggested an interaction between SelW and 14-3-3 proteins. In the present work, with the aid of NMR spectroscopy, we demonstrated specificity of this interaction and iden¬tified mobile loops in SelW as interacting surfaces. This finding sug¬gests that 14-3-3 are redox-regulated proteins

Journal clubs in the time of preprints.

Early-career researchers can learn about peer review by discussing preprints at journal clubs and sending feedback to the authors

Journal clubs in the time of preprints

Early-career researchers can learn about peer review by discussing preprints at journal clubs and sending feedback to the authors

Mechanism of membrane interaction and disruption by α-synuclein

Parkinson's disease is a common progressive neurodegenerative condition, characterized by the deposition of amyloid fibrils as Lewy bodies in the substantia nigra of affected individuals. These insoluble aggregates predominantly consist of the protein α-synuclein. There is increasing evidence suggesting that the aggregation of α-synuclein is influenced by lipid membranes and, vice versa, the membrane integrity is severely affected by the presence of bound aggregates. Here, using the surface-sensitive imaging technique supercritical angle fluorescence microscopy and Förster resonance energy transfer, we report the direct observation of α-synuclein aggregation on supported lipid bilayers. Both the wild-type and the two mutant forms of α-synuclein studied, namely, the familiar variant A53T and the designed highly toxic variant E57K, were found to follow the same mechanism of polymerization and membrane damage. This mechanism involved the extraction of lipids from the bilayer and their clustering around growing α-synuclein aggregates. Despite all three isoforms following the same pathway, the extent of aggregation and their effect on the bilayers was seen to be variant and concentration dependent. Both A53T and E57K formed cross-β-sheet aggregates and damaged the membrane at submicromolar concentrations. The wild-type also formed aggregates in this range; however, the extent of membrane disruption was greatly reduced. The process of membrane damage could resemble part of the yet poorly understood cellular toxicity phenomenon in vivo