Skeletal growth and the changing genetic landscape during childhood and adulthood

Growth, development, and decline of the human skeleton are of central importance to physical anthropology. All processes of skeletal growth (longitudinal growth as well as gains and losses of bone mass) are subjected to environmental and genetic influences. These influences, and their relative contributions to the phenotype, can be asserted at any stage of life. We present here the gross phenotypic and genetic landscapes of four skeletal traits, and show how they vary across the life span. Phenotypic sex differences are found in bone diameter and cortical index (a ratio of cortical thickness over bone diameter) at a very early age and continue throughout most of life. Sexual dimorphism in summed cortical thickness and bone length, however, is not evident until shortly after the pubertal growth spurt. Genetic contributions (heritability) to these skeletal phenotypes are generally moderate to high. Bone length and bone diameter (which both scale with body size) tend to have the highest heritability, with heritability of bone length fairly stable across ages (with a notable dip in early childhood) and that of bone diameter peaking in early childhood. The bone traits summed cortical thickness and cortical index that may better reflect bone mass, a more plastic phenomenon, have slightly lower genetic influences, on average. Results from our phenotypic and genetic landscapes serve three key purposes: 1) demonstration of the integrated nature of the genetic and environmental underpinnings of skeletal form, 2) identification of periods of bone's relative sensitivity to genetic and environmental influences, 3) and stimulation of hypotheses predicting the effects of exposure to environmental variables on the skeleton, given variation in the underlying genetic architecture. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.     

Novel 9a-carbamoyl- and 9a-thiocarbamoyl-3-decladinosyl-6-hydroxy and 6-methoxy derivatives of 15-membered macrolides

An efficient method for the synthesis of diverse 9a-carbamoyl- and 9a-thiocarbamoyl-3-decladinosyl-6-hydroxy and 3-decladinosyl-6-methoxy derivatives of 15-membered azalides has been developed. These derivatives bear various alkyl and aryl groups attached to macrolide scaffold through urea or thiourea moieties at 9a position. Chemical transformations of hydroxy group at position C-3 afforded range of ketolides, anhydrolides, hemiketals, cyclic ethers, and acylides. It has been shown that 6-hydroxy and 6-methoxy derivatives undergo different chemical transformations under otherwise identical reaction conditions. Antimicrobial properties of prepared compounds were evaluated.     

Tailored Electron Transfer Pathways in Aucore/Ptshell–Graphene Nanocatalysts for Fuel Cells

Au_core/Pt_shell–graphene catalysts (G‐Cys‐Au@Pt) are prepared through chemical and surface chemical reactions. Au–Pt core–shell nanoparticles (Au@Pt NPs) covalently immobilized on graphene (G) are efficient electrocatalysts in low‐temperature polymer electrolyte membrane fuel cells. The 9.5 ± 2 nm Au@Pt NPs with atomically thin Pt shells are attached on graphene via l ‐cysteine (Cys), which serves as linkers controlling NP loading and dispersion, enhancing the Au@Pt NP stability, and facilitating interfacial electron transfer. The increased activity of G‐Cys‐Au@Pt, compared to non‐chemically immobilized G‐Au@Pt and commercial platinum NPs catalyst (C‐Pt), is a result of (1) the tailored electron transfer pathways of covalent bonds integrating Au@Pt NPs into the graphene framework, and (2) synergetic electronic effects of atomically thin Pt shells on Au cores. Enhanced electrocatalytic oxidation of formic acid, methanol, and ethanol is observed as higher specific currents and increased stability of G‐Cys‐Au@Pt compared to G‐Au@Pt and C–Pt. Oxygen reduction on G‐Cys‐Au@Pt occurs at 25 mV lower potential and 43 A g_Pt^?1 higher current (at 0.9 V vs reversible hydrogen electrode) than for C–Pt. Functional tests in direct fomic acid, methanol and ethanol fuel cells exhibit 95%, 53%, and 107% increased power densities for G‐Cys‐Au@Pt over C–Pt, respectively.     

Discovery of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides active against efflux-mediated resistant Streptococcus pneumoniae

A series of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides, were discovered, structurally characterized and biologically evaluated. They have shown good antibacterial activity against selected Gram-positive and Gram-negative bacterial strains. These include N″ substituted 9a-(N′-carbamoyl-γ-aminopropyl)- (6a,c), 9a-(N′-thiocarbamoyl-γ-aminopropyl)- (7a,e), 9a-[N′-(β-cyanoethyl)-N′-(carbamoyl-γ-aminopropyl)]- (9a-c, 9g) 9a-[N′-(β-cyanoethyl)-N′-(thiocarbamoyl-γ-aminopropyl)]-derivatives (10d-f) of 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3).Among the synthesized compounds thiourea 7a and urea 9b have shown substantially improved activity comparable to azithromycin (1) and significantly better activity than the 3-decladinosyl-azithromycin (2) and the parent 3-cladinosyl analogues against efflux-mediated resistant S. pneumoniae.