•Secondary, reversion mutations in genes can restore protein function.•Reversion mutations can underlie resistance to therapies such as PARP inhibitors.•Reversion mutations arise during the course of treatment.
Two-pore domain, outwardly rectifying potassium (TOK) channels are exclusively expressed in fungi. Human fungal pathogen TOK channels are potential antifungal targets, but TOK channel modulation in general is poorly understood. Here, we discovered that TOK (CaTOK) is regulated by extracellular pH, in contrast to TOK channels from other fungal species tested.
Introduction: Modification of natural enzymes to introduce new properties and enhance existing ones is a central challenge in bioengineering. This study is focused on the development of Taq polymerase mutants that show enhanced reverse transcriptase (RTase) activity while retaining other desirable properties such as fidelity, 5'- 3' exonuclease activity, effective deoxyuracyl incorporation, and tolerance to locked nucleic acid (LNA)-containing substrates. Our objective was to use AI-driven rational design combined with multiparametric wet-lab analysis to identify and validate Taq polymerase mutants with an optimal combination of these properties.
Radiotherapy is an integral modality in treating human cancers, but radioresistance remains a clinical challenge due to the involvement of multiple intrinsic cellular and extrinsic tumour microenvironment factors that govern radiosensitivity. To study the intrinsic factors that are associated with cancer radioresistance, we established 4 radioresistant prostate (22Rv1 and DU145) and head and neck cancer (FaDu and HK1) models by irradiating their wild-type parentals to 90 Gy, mimicking the fractionated radiotherapy schema that is often using in the clinic, and performed whole exome and transcriptome sequencing of the radioresistant and wild-type models. Comparative genomic analyses detected the enrichment of mismatch repair mutational signatures (SBS6, 14, 15, 20) across all the cell lines and several non-synonymous single nucleotide variants involved in pro-survival pathways.
AbstractTheoretical studies from diverse areas of population biology have shown that demographic stochasticity can substantially impact evolutionary dynamics in finite populations, including scenarios where traits that are disfavored by natural selection can nevertheless increase in frequency through the course of evolution. Here, we analytically describe the eco-evolutionary dynamics of finite populations from demographic first principles. We investigate how noise-induced effects can alter the evolutionary fate of populations in which total population size may vary stochastically over time.
Department of Urology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Uromonitor and urinary telomerase reverse transcriptase promoter mutation droplet digital PCR (uTERTpm ddPCR) are non-invasive tests designed to detect bladder cancer in urine. We aimed to compare the diagnostic performance of uTERTpm ddPCR, Uromonitor and urine cytology in detecting bladder cancer. Urine samples were collected prospectively from patients diagnosed with primary (n = 74) and recurrent bladder cancer (n = 20) or benign urological conditions (n = 48) prior to surgical resection.
