Cyclometalated ruthenium(II) complexes of benzo[h]quinoline (bzqH)[Ru(bzq)(NCMe)4], [Ru(bzq)(LL)(NCMe)2], and [Ru(bzq)(LL)2] (LL = bpy, phen)

Cyclometalation of benzo[h]quinoline (bzqH) by [RuCl(μ-Cl)(η⁶-C₆H₆)]₂ in acetonitrile occurs in a similar way to that of 2-phenylpyridine (phpyH) to afford [Ru(bzq)(MeCN)₄]PF₆ (3) in 52% yield. The properties of 3 containing ‘non-flexible’ benzo[h]quinoline were compared with the corresponding [Ru(phpy)(MeCN)₄]PF₆ (1) complex with ‘flexible’ 2-phenylpyridine. The [Ru(phpy)(MeCN)₄]PF₆ complex is known to react in MeCN solvent with ‘non-flexible’ diimine 1,10-phenanthroline to form [Ru(phpy)(phen)(MeCN)₂]PF₆, being unreactive toward ‘flexible’ 2,2′-bipyridine under the same conditions. In contrast, complex 3 reacts both with phen and bpy in MeCN to form [Ru(bzq)(LL)(MeCN)₂]PF₆ {LL = bpy (4) and phen (5)}. Similar reaction of 3 in methanol results in the substitution of all four MeCN ligands to form [Ru(bzq)(LL)₂]PF₆ {LL = bpy (6) and phen (7)}. Photosolvolysis of 4 and 5 in MeOH occurs similarly to afford [Ru(bzq)(LL)(MeCN)(MeOH)]PF₆ as a major product. This contrasts with the behavior of [Ru(phpy)(LL)(MeCN)₂]PF₆, which lose one and two MeCN ligands for LL = bpy and phen, respectively. The results reported demonstrate a profound sensitivity of properties of octahedral compounds to the flexibility of cyclometalated ligand. Analogous to the 2-phenylpyridine counterparts, compounds 4-7 are involved in the electron exchange with reduced active site of glucose oxidase from Aspergillus niger. Structure of complexes 4 and 6 was confirmed by X-ray crystallography.     

Frequency of natural regulatory CD4+CD25+ T lymphocytes determines the outcome of tolerance across fully mismatched MHC barrier through linked recognition of self and allogeneic stimuli

We show in this study that long-term tolerance to allogeneic skin grafts can be established in the absence of immunosuppression by the combination of the following elements: 1) augmenting the frequency of regulatory CD4(+)CD25(+) T cells (Treg) and 2) presentation of the allogeneic stimuli through linked recognition of allo- and self-epitopes on semiallogeneic F(1) APCs. BALB/c spleen cells enriched for CD4(+)CD25(+) T lymphocytes were transferred either to BALB/c nu/nu mice or to BALB/c nu/nu previously injected with F(1)(BALB/c x B6.Ba) spleen cells, or else grafted with F(1)(BALB/c x B6.Ba) skin (chimeric BALB/c nu/nu-F(1)). Chimeric BALB/c nu/nu-F(1) reconstituted with syngeneic CD25(+)-enriched spleen cells were unable to reject the previously transferred F(1)(BALB/c x B6.Ba) spleen cells or F(1)(BALB/c x B6.Ba) skin grafts, and a specific tolerance to a secondary B6 graft was obtained, with rejection of third-party CBA grafts. BALB/c nu/nu mice reconstituted only with syngeneic CD25(+)-enriched spleen cells rejected both B6 and CBA skin grafts. In contrast, when chimeric BALB/c nu/nu-F(1) were reconstituted with spleen populations comprising normal frequencies of Treg cells, the linked recognition of allo and self resulted in breaking of self tolerance and rejection of syngeneic grafts, strongly suggesting that linked recognition works in both directions, either to establish tolerance to allo, or to break tolerance to self, the critical parameter being the relative number of Treg cells.     

Conservation genetics of South American aquatic mammals: an overview of gene diversity,population structure,phylogeography, non‐invasive methods and forensics

• 1 Most aquatic mammals have high dispersal potential, and there are often severe conservation concerns related to their legal or illegal harvesting. Therefore, economic, social and forensic factors often arise in decisions relating to their population management. Molecular markers are essential tools in modern conservation genetics, revealing previously unknown aspects of aquatic mammal behaviour, natural history, population structure and demography. Molecular markers also have been used to define management units, to recognize taxonomic units, to conduct forensic analyses and to control illegal wildlife trade, providing valuable information for decision‐making in wildlife conservation and management.
• 2 We review studies published in peer‐reviewed journals between 1993 and 2010, in which genetic approaches have been applied to conservation‐related issues involving natural populations of 25 species of aquatic mammals in South America. These studies cover just 34% of the 70 aquatic mammal species recorded in South America.
• 3 Most of the studies are related to population structure, phylogeography, gene flow and dispersal movements. In addition, recent findings relate to evolutionarily significant units, management units, forensics and conservation policy.
• 4 Finally, we look to the future and, based on numbers of studies and conservation concerns, suggest which species, geographic areas and genetic studies should be prioritized. Moreover, we discuss constraints on research and suggest collaborative works that would provide critical information towards the effective conservation and management of aquatic mammals in South America.

     

An apoA-I mimetic peptibody generates HDL-like particles and increases alpha-1 HDL subfraction in mice

The aim of this study is to investigate the capability of an apoA-I mimetic with multiple amphipathic helices to form HDL-like particles in vitro and in vivo. To generate multivalent helices and to track the peptide mimetic, we have constructed a peptibody by fusing two tandem repeats of 4F peptide to the C terminus of a murine IgG Fc fragment. The resultant peptidbody, mFc-2X4F, dose-dependently promoted cholesterol efflux in vitro, and the efflux potency was superior to monomeric 4F peptide. Like apoA-I, mFc-2X4F stabilized ABCA1 in J774A.1 and THP1 cells. The peptibody formed larger HDL particles when incubated with cultured cells compared with those by apoA-I. Interestingly, when administered to mice, mFc-2X4F increased both pre-β and α-1 HDL subfractions. The lipid-bound mFc-2X4F was mostly in the α-1 migrating subfraction. Most importantly, mFc-2X4F and apoA-I were found to coexist in the same HDL particles formed in vivo. These data suggest that the apoA-I mimetic peptibody is capable of mimicking apoA-I to generate HDL particles. The peptibody and apoA-I may work cooperatively to generate larger HDL particles in vivo, either at the cholesterol efflux stage and/or via fusion of HDL particles that were generated by the peptibody and apoA-I individually.     

Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia

In an attempt to understand the applicability of various animal models to dyslipidemia in humans and to identify improved preclinical models for target discovery and validation for dyslipidemia, we measured comprehensive plasma lipid profiles in 24 models. These included five mouse strains, six other nonprimate species, and four nonhuman primate (NHP) species, and both healthy animals and animals with metabolic disorders. Dyslipidemic humans were assessed by the same measures. Plasma lipoprotein profiles, eight major plasma lipid fractions, and FA compositions within these lipid fractions were compared both qualitatively and quantitatively across the species. Given the importance of statins in decreasing plasma low-density lipoprotein cholesterol for treatment of dyslipidemia in humans, the responses of these measures to simvastatin treatment were also assessed for each species and compared with dyslipidemic humans. NHPs, followed by dog, were the models that demonstrated closest overall match to dyslipidemic humans. For the subset of the dyslipidemic population with high plasma triglyceride levels, the data also pointed to hamster and db/db mouse as representative models for practical use in target validation. Most traditional models, including rabbit, Zucker diabetic fatty rat, and the majority of mouse models, did not demonstrate overall similarity to dyslipidemic humans in this study.     

First polymorphisms in JY-1 gene in cattle (Bos taurus indicus) and their association with sexual precocity and growth traits

Protein JY-1 is a bovine oocyte-specific protein that regulates granulosa cell function and is involved in early embryonic development, influencing the chance of pregnancy. This study investigated molecular markers for the JY-1 gene. Seven SNPs were identified in exon 3 of the gene. The positions of the SNPs in the exon and the respective substitutions are: 163 (T/C), 281 (T/C), 321 (T/C), 532 (T/C), 652 (A/G), 679 (T/C), and 722 (G/C) (GenBank: JN592587 and JF262042.2). SNP 163 is located in a coding region and causes a proline-to-leucine substitution. The other SNPs are located in the 3′UTR region. SNPs 163, 281, 321, and 679 were genotyped in 297 Nellore heifers and the haplotypes were constructed. The haplotypes of JY-1 were not correlated with the traits studied at 5?%.     

The Socioecology of Network Scaling Ratios in the Multilevel Society of Hamadryas Baboons (Papio hamadryas hamadryas)

Multilevel or modular societies characterize a range of mammalian taxa, allowing social groups to fission and fuse in response to ecological factors. The modular society of hamadryas baboons has previously been shown to consist of 4 levels: troop, band, clan, and one-male unit (OMU). A recent study by Hill et al. (Biology Letters 4:748–751, 2008) revealed a mean scaling ratio across successive levels of multilevel societies of ca. 3; this was consistent across elephants, orca, geladas, and hamadryas baboons. Here we reanalyze the scaling ratio for hamadryas baboons with previously unavailable data from Filoha. Our analysis revealed a mean scaling ratio for hamadryas of 3.28 without data on the hamadryas clan layer of organization at Filoha, but a ratio of 6.17 with these data included. This discrepancy is due to the large clan and band sizes at Filoha yielding a larger than average gap between the OMU and the clan. Further analysis revealed subsets of OMUs within clans, suggesting a 5th level of society in this population. When this 5th layer of social structure is included in the analysis, the scaling ratio at Filoha is consistent with that of other hamadryas populations and other taxa. These results suggest that a consistent mammalian scaling ratio can be used to detect previously hidden levels of organization within societies and to predict their sizes in taxa for which detailed behavioral data are not available.     

Decreased sensory responses in osteocalcin null mutant mice imply neuropeptide function

Osteocalcin, the most abundant member of the family of extracellular mineral binding gamma-carboxyglutamic acid proteins is synthesized primarily by osteoblasts. Its affinity for calcium ions is believed to limit bone mineralization. Several of the numerous hormones that regulate synthesis of osteocalcin, including glucocorticoids and parathyroid hormone, are also affected by stressful stimuli that require energy for an appropriate response. Based on our observations of OC responding to stressful sensory stimuli, the expression of OC in mouse and rat sensory ganglia was confirmed. It was thus hypothesized that the behavioral responses of the OC knockout mouse to stressful sensory stimuli would be abnormal. To test this hypothesis, behaviors related to sensory aspects of the stress response were quantified in nine groups of mice, aged 4-14 months, comparing knockout with their wild-type counterparts in six distinctly different behavioral tests. Resulting data indicated the following statistically significant differences: open field grooming frequency following saline injection, wild-type > knockout; paw stimulation with Von Frey fibers, knockout < wild-type; balance beam, knockout mobility < WT; thermal sensitivity to heat (tail flick), knockout < wild-type; and cold, knockout < wild-type. Insignificant differences in hanging wire test indicate that these responses are unrelated to reduced muscle strength. Each of these disparate environmental stimuli provided data indicating alterations of responses in knockout mice that suggest participation of osteocalcin in transmission of information about those sensory stimuli.