PM534, an Optimized Target-Protein Interaction Strategy through the Colchicine Site of Tubulin.

Targeting microtubules is the most effective wide-spectrum pharmacological strategy in antitumoral chemotherapy, and current research focuses on reducing main drawbacks: neurotoxicity and resistance. PM534 is a novel synthetic compound derived from the Structure-Activity-Relationship study on the natural molecule PM742, isolated from the sponge of the , family , genus (du Bocage 1869). PM534 targets the entire colchicine binding domain of tubulin, covering four of the five centers of the pharmacophore model.

Modulation of taxane binding to tubulin curved and straight conformations by systematic 3'N modification provides for improved microtubule binding, persistent cytotoxicity and in vivo potency.

The taxane class of microtubule stabilizers are some of the most effective and widely used chemotherapeutics. The anticancer activity of taxanes arises from their ability to induce tubulin assembly by selectively recognizing the curved (c-) conformation in unassembled tubulin as compared to the straight (s-) conformation in assembled tubulin. We first designed and synthesized a series of 3'N-modified taxanes bearing covalent groups.

Enzyme adaptation to habitat thermal legacy shapes the thermal plasticity of marine microbiomes.

Microbial communities respond to temperature with physiological adaptation and compositional turnover. Whether thermal selection of enzymes explains marine microbiome plasticity in response to temperature remains unresolved. By quantifying the thermal behaviour of seven functionally-independent enzyme classes (esterase, extradiol dioxygenase, phosphatase, beta-galactosidase, nuclease, transaminase, and aldo-keto reductase) in native proteomes of marine sediment microbiomes from the Irish Sea to the southern Red Sea, we record a significant effect of the mean annual temperature (MAT) on enzyme response in all cases.

COVID-SCORE Spain: public perceptions of key government COVID-19 control measures.

Background: Spain was initially one of the countries most affected by the coronavirus disease 2019 (COVID-19) pandemic. In June 2020, the COVID-SCORE-10 study reported that the Spanish public's perception of their government's response to the pandemic was low. This study examines these perceptions in greater detail.

Harnessing DNA for nanothermometry.

Temperature measurement at the nanoscale has brought insight to a wide array of research interests in modern chemistry, physics, and biology. These measurements have been enabled by the advent of nanothermometers, which relay nanoscale temperature information through the analysis of their intrinsic photophysical behavior. In the past decade, several nanothermometers have been developed including dyes, nanodiamonds, fluorescent proteins, nucleotides, and nanoparticles.