Synthesis and biological activities of phenyl piperazine-based peptidomimetic growth hormone secretagogues

A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substituent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.     

Prenatal diagnosis of trisomy 13 on fetal cells obtained from maternal blood after minor enrichment

In a pilot study to establish fetal nucleated red blood cell (NRBC) detection in maternal blood, trisomy 13 was diagnosed by FISH analysis at 11 weeks' gestation. The NRBCs were detected after a single-step ficoll density gradient enrichment. In blood samples taken both before and after CVS, 52 and 80 NRBCs, respectively, were found to be positive for fetal haemoglobin. In 47 per cent of these cells, FISH analysis for X and Y chromosomes confirmed the fetal sex. Moreover, 48 per cent of these NRBCs showed three fluorescent signals for a chromosome 13 probe, which confirmed the diagnosis of trisomy 13, previously detected at CVS karyotyping. This is the first report of non-invasive prenatal diagnosis of trisomy 13, i.e., pre-CVS, in the first trimester. The high number of fetal NRBCs detected indicates a connection with aneuploidy, probably due to early impairment of the feto-maternal barrier.     

Insulin-like growth factor binding protein-1 at mouse neuromuscular synapses

The insulin-like growth factor (IGF) signaling system includes the growth factors and their cell surface receptors, along with circulating IGF binding proteins (IGFBPs) that may alter and modulate the action of these neurotrophic hormones. These IGFBPs, along with IGFs and receptors, have been detected in various tissues including the brain. In this study, using polyclonal antibody to human IGFBP-1 or bovine IGFBP-2, we found that mouse muscle extracts contain similar-sized proteins that cross-react with these antibodies on Western immunoblots. After establishing that these antibodies reacted with the homologous murine IGFBPs, we performed immunocytochemistry to demonstrate the localization of IGFBP-1 at the neuromuscular junction, a model nicotinic, cholinergic synapse, as well as within intramuscular nerves. IGFBP-2, a distinct macromolecule, is present on the surface of muscle fibers and is not present within synapses or nerves.     

Antimetabolite-induced increases in the invasive capacity of murine leukaemia L1210 cells

Pretreatment of murine leukaemia L1210 cells with non-lethal concentrations of various antimetabolites increased the in vitro invasive capacity of these cells into monolayers of rat embryo fibroblasts. The increase in invasive capacity was partly correlated with the induced cell cycle arrest. The concomitant increase in cell surface fucosylation and inhibition of invasion with sulphate indicate a role for glycoproteins in this process. Our results suggest that treatment with antimetabolites may lead to a more aggressive phenotype by altering cell surface properties.     

Local‐scale Benefits of River Connectivity Restoration Planning Beyond Jurisdictional Boundaries

Conservation planning aims to optimize outcomes for select species or ecosystems by directing resources toward high‐return sites. The possibility that local benefits might be increased by directing resources beyond the focal area is rarely considered. We present a case study of restoring river connectivity for migratory fish of the Great Lakes Basin by removing dams and road crossings within municipal jurisdictions versus their broader watersheds. We found that greater river connectivity could often be achieved by considering both intra‐jurisdictional and extra‐jurisdictional barriers. Focusing on jurisdictional barriers alone generally forfeited <20% (median = 0%) of habitat gains for those who value solely habitat gains within the jurisdiction, but >75% (median = 100%) for planners who value larger‐scale habitat gains. Similarly, cost savings tended to be between ?50% and +50%, but in some cases were very negative. Our study underscores the local‐scale benefits of broadening restoration investments, especially for decision makers of the Great Lakes Basin and contributes to a discussion of appropriate and efficient scales of conservation planning. Copyright © 2017 John Wiley & Sons, Ltd.     

Void formation in a filled SBR rubber determined by small-angle X-ray scattering

Two commercial styrene-butadiene (SBR) latexes were used to prepare a model filled material consisting of glassy SBR filler particles about 1000 Å in diameter embedded in a rubbery SBR matrix crosslinked by γ-radiation. When transparent specimens of this material were extended, voiding occurred, as evidenced by stress whitening and greatly enhanced X-ray scattering intensity. More voids were formed at higher rates of extension, but voids disappeared when specimens were relaxed. The effects of filler content and cure time of the matrix on the size and number of voids formed were determined by low-angle X-ray scattering for a constant extension rate and a constant extension ratio λ = 1.6. The number of voids measured by X-ray scattering intensity decreased rapidly with time over the 3-h period of measurement. The number of voids remaining 1 h after extension increased about 40 times as filler content was increased from 15% to 50%. Increasing the cure time from 24 to 96 h increased the number of voids about four times. In contrast, the radius of gyration of the voids formed (250–350 Å) did not depend strongly on time, nor did it depend strongly on the filler content or the cure time of the matrix. Stress relaxation measurements made under the same conditions as X-ray scattering measurements showed effects typical of filled materials. However, the relaxation of stress (which followed a power law decay) was much slower than the decay of the number of voids as measured by X-ray scattering intensity.     

Engineering Analysis and Design with ALE-VMS and Space–Time Methods

Flow problems with moving boundaries and interfaces include fluid–structure interaction (FSI) and a number of other classes of problems, have an important place in engineering analysis and design, and offer some formidable computational challenges. Bringing solution and analysis to them motivated the Deforming-Spatial-Domain/Stabilized Space–Time (DSD/SST) method and also the variational multiscale version of the Arbitrary Lagrangian–Eulerian method (ALE-VMS). Since their inception, these two methods and their improved versions have been applied to a diverse set of challenging problems with a common core computational technology need. The classes of problems solved include free-surface and two-fluid flows, fluid–object and fluid–particle interaction, FSI, and flows with solid surfaces in fast, linear or rotational relative motion. Some of the most challenging FSI problems, including parachute FSI, wind-turbine FSI and arterial FSI, are being solved and analyzed with the DSD/SST and ALE-VMS methods as core technologies. Better accuracy and improved turbulence modeling were brought with the recently-introduced VMS version of the DSD/SST method, which is called DSD/SST-VMST (also ST-VMS). In specific classes of problems, such as parachute FSI, arterial FSI, ship hydrodynamics, fluid–object interaction, aerodynamics of flapping wings, and wind-turbine aerodynamics and FSI, the scope and accuracy of the FSI modeling were increased with the special ALE-VMS and ST FSI techniques targeting each of those classes of problems. This article provides an overview of the core ALE-VMS and ST FSI techniques, their recent versions, and the special ALE-VMS and ST FSI techniques. It also provides examples of challenging problems solved and analyzed in parachute FSI, arterial FSI, ship hydrodynamics, aerodynamics of flapping wings, wind-turbine aerodynamics, and bridge-deck aerodynamics and vortex-induced vibrations.     

Atomic force microscopy study of biaxially oriented polypropylene films

Atomic force microscopy (AFM) uses a very sharp pointed mechanical probe to collect real-space morphological information of solid surfaces. AFM was used in this study to image the surface morphology of a biaxially oriented polypropylene film. The polymer film is characterized by a nanometer-scale, fiberlike network structure, which reflects the drawing process used during the fabrication of the film. AFM was used to study polymer-surface treatment to improve wettability by exposing the polymer to ozone with or without ultraviolet (UV) irradiation. Surface-morphology changes observed by AFM are the result of the surface oxidation induced by the treatment. Due to the topographic features of the polymer film, the fiberlike structure has been used to check the performance of the AFM tip. An AFM image is a mixture of the surface morphology and the shape of the AFM tip. Therefore, it is important to check the performance of a tip to ensure that the AFM image collected reflects the true surface features of the sample, rather than contamination on the AFM tip.     

The expanding small heat-shock protein family, and structure predictions of the conserved "alpha-crystallin domain"

The ever-increasing number of proteins identified as belonging to the family of small heat-shock proteins (shsps) and alpha-crystallins enables us to reassess the phylogeny of this ubiquitous protein family. While the prokaryotic and fungal representatives are not properly resolved, most of the plant and animal shsps and related proteins are clearly grouped in distinct clades, reflecting a history of repeated gene duplications. The members of the shsp family are characterized by the presence of a conserved homologous "alpha-crystallin domain," which sometimes is present in duplicate. Predictions are made of secondary structure and solvent accessibility of this domain, which together with hydropathy profiles and intron positions support the presence of two similar hydrophobic beta-sheet-rich motifs, connected by a hydrophilic alpha-helical region. Together with an overview of the newly characterized members of the shsp family, these data help to define this family as being involved as stable structural proteins and as molecular chaperones during normal development and induced under pathological and stressful conditions.