Convergent evolution of viral-like Borg archaeal extrachromosomal elements and giant eukaryotic viruses.

Unlabelled: Borgs are huge extrachromosomal elements of anaerobic methane-oxidizing archaea. They exist in exceedingly complex microbiomes, lack cultivated hosts and have few protein functional annotations, precluding their classification as plasmids, viruses or other. Here, we used structure prediction methods to investigate potential roles for ∼10,000 Borg proteins.

Secondary analysis of whole genomes reveals diverse antimicrobial resistance profiles.

Antimicrobial resistance (AMR) in microorganisms is an ongoing threat to human health across the globe. To better characterize the AMR profiles of six strains of , we performed a secondary analysis that consisted of the following steps: 1) download fastq files from the Sequence Read Archive, 2) perform a genome assembly from the sequencing reads, 3) annotate the assembled contigs, 4) predict the presence of antimicrobial resistance genes. We predicted the presence of 75 unique genes that conferred resistance against 22 unique antimicrobial compounds.

Temperature Response of Metabolic Activity of an Antarctic Nematode.

Because of climate change, the McMurdo Dry Valleys of Antarctica (MCM) have experienced an increase in the frequency and magnitude of summer pulse warming and surface ice and snow melting events. In response to these environmental changes, some nematode species in the MCM have experienced steady population declines over the last three decades, but , a mesophilic nematode species, has responded with a steady increase in range and abundance. To determine how responds to increasing temperatures, we measured metabolic heat and CO production rates and calculated O consumption rates as a function of temperature at 5 °C intervals from 5 to 50 °C.

A novel series of potent and selective PDE5 inhibitors with potential for high and dose-independent oral bioavailability.

Sildenafil (5-[2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one), a potent and selective phosphodiesterase type 5 (PDE5) inhibitor, provided the first oral treatment for male erectile dysfunction. The objective of the work reported in this paper was to combine high levels of PDE5 potency and selectivity with high and dose-independent oral bioavailability, to minimize the impact on the C(max) of any interactions with coadministered drugs in the clinic. This goal was achieved through identification of a lower clearance series with a high absorption profile, by replacing the 5'-piperazine sulfonamide in the sildenafil template with a 5'-methyl ketone.

Regulatory roles of the N-terminal domain based on crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligands.

Pyruvate dehydrogenase kinase (PDHK) regulates the activity of the pyruvate dehydrogenase multienzyme complex. PDHK inhibition provides a route for therapeutic intervention in diabetes and cardiovascular disorders. We report crystal structures of human PDHK isozyme 2 complexed with physiological and synthetic ligands.