Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.

Background: Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, but their existence and relative frequency in clinical disease are unclear, as is how to target resistance.

Patients And Methods: Longitudinal mutation and methylation profiling of circulating tumour (ct)DNA was carried out in 47 patients with metastatic BRCA1-, BRCA2- or PALB2-mutant breast cancer treated with HRD-targeted therapy who developed progressive disease-18 patients had primary resistance and 29 exhibited response followed by resistance.

MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells.

The PSMC3IP-MND1 heterodimer promotes meiotic D loop formation before DNA strand exchange. In genome-scale CRISPR-Cas9 mutagenesis and interference screens in mitotic cells, depletion of PSMC3IP or MND1 causes sensitivity to poly (ADP-Ribose) polymerase inhibitors (PARPi) used in cancer treatment. PSMC3IP or MND1 depletion also causes ionizing radiation sensitivity.

Thermal and Mechanical Properties of Concrete Incorporating Silica Fume and Waste Rubber Powder.

Using waste rubber tires for concrete production will reduce the demand for natural aggregate and help to reduce environmental pollution. The main challenge of using waste rubber tires in concrete is the deterioration of mechanical properties, due to poor bonding between rubber and cement matrix. This research aims to evaluate the mechanical and thermal properties of rubberised concrete produced by using different proportions of rubber powder and silica fume.

Potential application of spent mushroom compost (SMC) biochar as low-cost filtration media in heavy metal removal from abandoned mining water: a review.

Overpopulation and rapid development have put an increasing burden on the environment, leading to various water crisis. Importing water from abandoned mines as an alternative raw water source could be the next answer to alleviate water scarcity problems globally. However, due to its high heavy metals content, there is a need to find an economical and effective method to remove heavy metals before reusing it as potable water source.

The multifaceted hTR telomerase RNA from a structural perspective: Distinct domains of hTR differentially interact with protein partners to orchestrate its telomerase-independent functions.

Human telomerase progressively emerged as a multifaceted ribonucleoprotein complex with additional functions beyond telomeric repeat synthesis. Both the hTERT catalytic subunit and the hTR long non-coding RNA (lncRNA) subunit are engaged in highly regulated cellular pathways that, together, contribute to cell fitness and protection against apoptosis. We recently described a new role for hTR in regulating the abundance of replication protein A at telomeres, adding to the growing repertoire of hTR's functions.