Synthesis and in vitro evaluation of small-molecule [18F] labeled gonadotropin-releasing hormone (GnRH) receptor antagonists as potential PET imaging agents for GnRH receptor expression

Two novel small molecule gonadotropin-releasing hormone (GnRH) receptor antagonists (12 and 13) of the furamide-class were synthesized and evaluated in vitro for their receptor binding affinities for the rat GnRH receptor. Radiolabeling with no carrier added fluorine-18 of the appropriate precursors was investigated in a one-step reaction. Log P (Octanol/PBS pH 7.4) and serum stability of the compounds were investigated. The antagonists showed low nM affinity for the rat GnRH receptor. ¹⁸F-radiolabled compounds were obtained in high radiochemical purity (>95%) and specific activity (>75 GBq/μmol). These findings suggest this class of compounds holds promise as potential probes for PET targeting of GnRH-receptor expression.     

MV-mimicking micelles loaded with PEG-serine-ACP nanoparticles to achieve biomimetic intra/extra fibrillar mineralization of collagen in vitro

Since their discovery, matrix vesicles (MVs) containing minerals have received considerable attention for their role in the mineralization of bone, dentin and calcified cartilage. Additionally, MVs' association with collagen fibrils, which serve as the scaffold for calcification in the organic matrix, has been repeatedly highlighted. The primary purpose of the present study was to establish a MVs–mimicking model (PEG-S-ACP/micelle) in vitro for studying the exact mechanism of MVs-mediated extra/intra fibrillar mineralization of collagen in vivo. In this study, high-concentration serine was used to stabilize the amorphous calcium phosphate (S-ACP), which was subsequently mixed with polyethylene glycol (PEG) to form PEG-S-ACP nanoparticles. The nanoparticles were loaded in the polysorbate 80 micelle through a micelle self-assembly process in an aqueous environment. This MVs–mimicking model is referred to as the PEG-S-ACP/micelle model. By adjusting the pH and surface tension of the PEG-S-ACP/micelle, two forms of minerals (crystalline mineral nodules and ACP nanoparticles) were released to achieve the extrafibrillar and intrafibrillar mineralization, respectively. This in vitro mineralization process reproduced the mineral nodules mediating in vivo extrafibrillar mineralization and provided key insights into a possible mechanism of biomineralization by which in vivo intrafibrillar mineralization could be induced by ACP nanoparticles released from MVs. Also, the PEG-S-ACP/micelle model provides a promising methodology to prepare mineralized collagen scaffolds for repairing bone defects in bone tissue engineering.     

A convenient method of isoflavonone synthesis

Reaction of 2-hydroxydeoxybenzoins with bis(dimethylamino)methane in ethanol results in isoflavonones.     

The N-Terminal Region of the RecU Holliday Junction Resolvase Is Essential for Homologous Recombination

The RecU Holliday junction (HJ)-resolving enzyme is highly conserved in the Firmicutes phylum of bacteria. In Bacillus subtilis, the recU gene has two putative initiation codons, at positions 1 and 33. In rec⁺ cells, only the full-length RecU polypeptide (206 residues, 23.9 kDa) was detected even after different stress treatments. To address the relevance of the flexible N-terminus, we constructed mutant variants. Experiments in vivo revealed that recUΔ1-32 (which initiates at Met33 and encodes RecUΔ1-32) and recU31 (the conserved Arg31 residue was substituted with alanine to give RecUR31A) are genuine RecU mutants, rendering cells impaired in DNA repair and chromosomal segregation. RecU has three activities: It (i) cleaves HJs, (ii) anneals complementary strands and (iii) modulates RecA activities. RecUR31A binds and cleaves HJ DNA in vitro as efficiently as wild-type RecU, but RuvB·ATPγS·Mg²⁺ fails to stimulate the RecUR31A cleavage reaction. In contrast, RecUΔ1-32 forms unstable complexes with DNA and fails to cleave HJs. RecU and its variants are capable of promoting DNA strand annealing and exert a negative effect on deoxy-ATP-dependent RecA-mediated DNA strand exchange. This study shows that the flexible N-terminus of RecU is essential for protein activity.     

Anatomical site of pheromone accumulation and temporal pattern of pheromone emission in the ambrosia beetle Megaplatypus mutatus

Megaplatypus mutatus (Chapuis) is a native South American ambrosia beetle that attacks live hardwood trees (e.g. Populus spp.), causing important economic losses to commercial plantations. Male beetles release the main components of the sex pheromone, namely (+)‐6‐methyl‐5‐hepten‐2‐ol [(+)‐sulcatol, or retusol] and 6‐methyl‐5‐hepten‐2‐one (sulcatone), when colonizing suitable hosts. The hindgut is shown to be the anatomical site of pheromone accumulation within males, the enantiomeric composition of sulcatol in this tissue is 99%‐(+) and sulcatol is first detectable in this tissue on days 1–2 after gallery initiation. Peak accumulation of sulcatol occurs on days 5–12 after gallery initiation. Trace quantities of sulcatone are also observed during the same period. Both pheromone components are present in male emissions from three host species (Populus×canadensis, Populus alba and Casuarina stricta) between days 2 and 12 after gallery initiation, although sulcatone is always present in low concentrations. The temporal patterns of sulcatol and sulcatone accumulation or storage in male M. mutatus correspond to the temporal patterns of emission.     

Rhythms of fragrance emission in flowers

A method for the sampling of volatiles emitted by individual flowers is described. Sampling over periods of 3 h allowed the examination of diurnal changes in quantity and quality of fragrance. In the species studied, Odontoglossum constrictum Lindl., Citrus medica L., Hoya carnosa R. Br., and Stephanotis floribunda Brongs., the fragrance was characterized by a few major components accompanied by a larger number of minor components. Flowers of all species produced volatiles in a rhythmical, diurnal fashion. Whereas in detached flowers of O. constrictum and C. medica rhythmicity could be observed for up to four cycles, flowers of H. carnosa showed this phenomenon only when attached to the plant. Maxima of emission were observed during the day in C. medica and O. constrictum whereas in H. carnosa it occurred during the night. In S. floribunda a conspicuous asynchronism of the emission of different volatiles was observed, resulting in the rhythmical change of fragrance quality.     

Decrease of the hydraulic conductivity of sand columns by Methanosarcina barkeri

The extent to which a methanogen can clog sand columns was examined: two permeameters packed with clean quartz sand were sterilized, saturated with water, inoculated with Methanosarcina barkeri and percolated under upward flow conditions. After approx. 5 months, the hydraulic conductivity of the sand had decreased to 3% and 25% of the highest values measured earlier. At that point, gas-filled regions in the sand were clearly visible through the transparent walls of the permeameters, and methane bubbles were continuously released from the columns into the effluent. Scanning electron microscopy observations and biomass assays indicated that cell mass accumulation did not contribute significantly to the observed decrease of the hydraulic conductivity. This decrease was therefore attributed to pore blocking due to the entrapment of methane bubbles.D. Sanchez de Lozada and P. Baveye are with the Department of Soil, Crop and Atmospheric Sciences, Bradfield Hall, Cornell University, Ithaca, NY 13853, USA; P. Vandevivere is with the College of Marine Studies, University of Delaware, Lewes, DE 19958, USA. S. Zinder is with the Department of Microbiology, Rice Hall, Cornell University, Ithaca, NY 14853, USA.