Aquablation of the Prostate for Symptomatic Benign Prostatic Hyperplasia: Early Results.

Aquablation is a novel technique for the surgical management of bladder outlet obstruction secondary to benign prostatic hyperplasia. Following first-in-man studies, a multicenter trial was conducted with results now out to 1 year. Aquablation resulted in a mean International Prostate Symptom Score improvement of 16 points (p < 0.01) and a mean maximum urinary flow rate increase from 8.7 to 18.3 ml/s (p < 0.01) at 12 months. Due to the precise prostate mapping, aquablation has also demonstrated favorable sexual and urinary outcomes with no new erectile dysfunction, retrograde ejaculation, or urinary incontinence as often experienced with other techniques. These improvements in functional outcomes at 12 months confirm that aquablation is a safe and effective alternative for BPH treatment.

Coordination polymers of CdII and PbII with croconate show remarkable differences in coordination patterns: a structural and spectroscopic study.

The croconate dianion is a highly versatile ligand with two tautomeric forms making it useful for building large superstructures in the solid state. The single-crystal X-ray structures of PbII- and CdII-croconate coordination polymers, namely catena-poly[[[diaqualead(II)]-µ-croconato-κ4O1,O2:O3,O4] monohydrate], {[Pb(C5O5)(H2O)2]·H2O}n, 1, and catena-poly[[triaquacadmium(II)]-µ-croconato-κ4O1,O2:O3,O4], [Cd(C5O5)(H2O)3]n, 2, have been determined. Both polymers form one-dimensional (1D) structures; 1 is a nonplanar 1D zigzag coordination polymer extended along the crystallographic b axis, whereas 2 is a planar 1D ribbon parallel to the [101] direction. In 2, three H2O molecules are coordinated directly to the metal atom, while in 1, only two H2O molecules are directly coordinated to the metal atom. A third interstitial H2O molecule is involved in hydrogen bonding with O atoms of the croconate ligands of an adjacent layer and other H2O molecules, resulting in stacked double layers parallel to the [105] plane. Solid-state FT-IR and solution UV-Vis spectra also substantiate the croconate coordination.

The equilibrium unfolding pathway of a (beta/alpha)8 barrel.

The (beta/alpha)(8) barrel is the most commonly occurring fold among enzymes. A key step towards rationally engineering (beta/alpha)(8) barrel proteins is to understand their underlying structural organization and folding energetics. Using misincorporation proton-alkyl exchange (MPAX), a new tool for solution structural studies of large proteins, we have performed a native-state exchange analysis of the prototypical (beta/alpha)(8) barrel triosephosphate isomerase. Three cooperatively unfolding subdomains within the structure are identified, as well as two partially unfolded forms of the protein. The C-terminal domain coincides with domains reported to exist in four other (beta/alpha)(8) barrels, but the two N-terminal domains have not been observed previously. These partially unfolded forms may represent sequential intermediates on the folding pathway of triosephosphate isomerase. The methods reported here should be applicable to a variety of other biological problems involving protein conformational changes.

Mapping of amino acid substitutions conferring herbicide resistance in wheat glutathione transferase.

We have used design of experiments (DOE) and systematic variance to efficiently explore glutathione transferase substrate specificities caused by amino acid substitutions. Amino acid substitutions selected using phylogenetic analysis were synthetically combined using a DOE design to create an information-rich set of gene variants, termed infologs. We used machine learning to identify and quantify protein sequence-function relationships against 14 different substrates. The resulting models were quantitative and predictive, serving as a guide for engineering of glutathione transferase activity toward a diverse set of herbicides. Predictive quantitative models like those presented here have broad applicability for bioengineering.

A molecular ruler for measuring quantitative distance distributions.

We report a novel molecular ruler for measurement of distances and distance distributions with accurate external calibration. Using solution X-ray scattering we determine the scattering interference between two gold nanocrystal probes attached site-specifically to a macromolecule of interest. Fourier transformation of the interference pattern provides a model-independent probability distribution for the distances between the probe centers-of-mass. To test the approach, we measure end-to-end distances for a variety of DNA structures. We demonstrate that measurements with independently prepared samples and using different X-ray sources are highly reproducible, we demonstrate the quantitative accuracy of the first and second moments of the distance distributions, and we demonstrate that the technique recovers complex distribution shapes. Distances measured with the solution scattering-interference ruler match the corresponding crystallographic values, but differ from distances measured previously with alternate ruler techniques. The X-ray scattering interference ruler should be a powerful tool for relating crystal structures to solution structures and for studying molecular fluctuations.

Rapid mapping of protein structure, interactions, and ligand binding by misincorporation proton-alkyl exchange.

Understanding protein conformation, interactions, and ligand binding is essential to all biological inquiry. We report a novel biochemical technique, called misincorporation proton-alkyl exchange (MPAX), that can be used to footprint protein structure at single amino acid resolution. MPAX exploits translational misincorporation of cysteine residues to generate probes for physical analysis. We apply MPAX to the triosephosphate isomerase (beta/alpha)(8) barrel, accurately determining its substrate-binding site, a protein-protein interaction surface, the solvent-accessible protein surface, and the stability of the barrel. Because MPAX requires only microgram quantities of material and is not limited by protein size, it is ideally suited for proteins not amenable to conventional structural methods, such as membrane proteins, partially folded or insoluble proteins, and large protein complexes.