Ligand substitution reactions of bis(μ-acetato)dichlorodicarbonyldiiridium(II)

Seven diiridium(II) complexes were synthesized by ligand substitution reactions of [Ir₂(μ-O₂CMe)₂Cl₂(CO)₂] (1) and [Ir₂(μ-O₂CMe)₂Cl₂(CO)₂(py)₂] (2).The reaction of 2 with the silver salt of a less coordinating anion, AgSbF₆, gave a cationic complex [Ir₂(μ-O₂CMe)₂Cl(CO)₂(py)₃]SbF₆ (3).A tricarbonyl cationic complex [Ir₂(μ-O₂CMe)₂(CO)₃Cl(py)₂]SbF₆ (4) was obtained under a CO atmosphere.Complex 2 reacted with AgO₂CCF₃ to give [Ir₂(μ-O₂CMe)₂Cl(O₂CCF₃)(CO)₂(py)₂] (5) in toluene.[Ir₂(μ-hiq)₂(CO)₂Cl₂] (Hhiq = 1-hydroxyisoquinoline, 6) was synthesized by the bridging-ligand substitution of 1 with Hhiq.Its axial adducts [Ir₂(μ-hiq)₂Cl₂(CO)₂L₂] (L = Mepy (4-methylpyridine), 7 or PPh₃, 8) were synthesized by addition of the ligands to a suspension of 6.In the structures of 7 and 8, two iridium atoms are bridged by two hiq ligands in a head-to-tail arrangement.The reaction of 1 with Hmhp (2-hydroxy-4-methylpyridine) led to triply bridged [Ir₂(μ-mhp)₃(CO)₂Cl(Hmhp)] (9).In complex 9, all the mhp ligands bridge between the Ir atoms in a head-to-head manner.The Ir-Ir distances of 3, 4, 5, 7 and 8 are 2.6047(7), 2.6216(9), 2.5899(9), 2.5933(5) and 2.634(2) Å, respectively, which are similar to those observed in[Ir₂(μ-O₂CMe)₂Cl₂(CO)₂L₂]. The Ir-Ir distance of 2.5512(4) Å in 9 is shorter than in the other complexes.     

Sodium n-butyrate induces prostaglandin synthetase activity in mastocytoma P-815 cells

Cultured mouse mastocytoma P-815 cells were treated with 1 mM sodium n-butyrate for 40 h. The treated cell homogenate showed high activities in synthesizing prostaglandin D2, E2, and F2 alpha. Such activities were virtually absent in untreated cell homogenate. Direct addition of sodium n-butyrate to the homogenate showed no effects. Pre-exposure of cells to acetylsalicylic acid did not diminish the effect of the subsequent treatment with sodium n-butyrate. These data suggest that sodium n-butyrate induces fatty acid cyclooxygenase in P-815 cells.     

Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors,S1P(2)/LP(B2)/EDG-5 and S1P(3)/LP(B3)/EDG-3

Five cognate G protein-coupled receptors (S1P(1-5)) have been shown to mediate various cellular effects of sphingosine 1-phosphate (S1P). Here we report the generation of mice null for S1P(2) and for both S1P(2) and S1P(3). S1P(2)-null mice were viable and fertile and developed normally. The litter sizes from S1P(2)S1P(3) double-null crosses were remarkably reduced compared with controls, and double-null pups often did not survive through infancy, although double-null survivors lacked any obvious phenotype. Mouse embryonic fibroblasts (MEFs) were examined for the effects of receptor deletions on S1P signaling pathways. Wild-type MEFs were responsive to S1P in activation of Rho and phospholipase C (PLC), intracellular calcium mobilization, and inhibition of forskolin-activated adenylyl cyclase. S1P(2)-null MEFs showed a significant decrease in Rho activation, but no effect on PLC activation, calcium mobilization, or adenylyl cyclase inhibition. Double-null MEFs displayed a complete loss of Rho activation and a significant decrease in PLC activation and calcium mobilization, with no effect on adenylyl cyclase inhibition. These data extend our previous findings on S1P(3)-null mice and indicate preferential coupling of the S1P(2) and S1P(3) receptors to Rho and PLC/Ca(2+) pathways, respectively. Although either receptor subtype supports embryonic development, deletion of both produces marked perinatal lethality, demonstrating an essential role for combined S1P signaling by these receptors.     

Ras-association domain family protein 6 induces apoptosis via both caspase-dependent and caspase-independent pathways

The Ras-association domain family (RASSF) comprises six members (RASSF1-6) that each harbors a RalGDS/AF-6 (RA) and Sav/RASSF/Hippo (SARAH) domain. The RASSF proteins are known as putative tumor suppressors but RASSF6 has not yet been studied. We have here characterized human RASSF6. Although RASSF6 has RA domain, it does not bind Ki-Ras, Ha-Ras, N-Ras, M-Ras, or TC21 under the condition that Nore1 (RASSF5) binds these Ras proteins. The message of RASSF6 is detected by RT-PCR in several cell lines including HeLa, MCF-7, U373, A549, and HepG2 cells, but the protein expression is low. The enhanced expression of RASSF6 causes apoptosis in HeLa cells. RASSF6 activates Bax and induces cytochrome C release. Caspase-3 activation is also induced, but the caspase inhibitor, Z-VAD-FMK, does not block RASSF6-mediated apoptosis. Apoptosis-inducing factor and endonuclease G are released from the mitochondria upon expression of RASSF6 and their releases are not blocked by Z-VAD-FMK. The knock down of RASSF6 partially blocks tumor necrosis factor-alpha-induced cell death in HeLa cells. These findings indicate that RASSF6 is implicated in apoptosis in HeLa cells and that it triggers both caspase-dependent and caspase-independent pathways.     

Howler monkey foraging ecology suggests convergent evolution of routine trichromacy as an adaptation for folivory

Primates possess remarkably variable color vision, and the ecological and social factors shaping this variation remain heavily debated. Here, we test whether central tenants of the folivory hypothesis of routine trichromacy hold for the foraging ecology of howler monkeys. Howler monkeys (genus Alouatta) and paleotropical primates (Parvorder: Catarrhini) have independently acquired routine trichromacy through fixation of distinct mid‐ to long‐wavelength‐sensitive (M/LWS) opsin genes on the X‐chromosome. The presence of routine trichromacy in howlers, while other diurnal neotropical monkeys (Platyrrhini) possess polymorphic trichromacy, is poorly understood. A selective force proposed to explain the evolution of routine trichromacy in catarrhines—reliance on young, red leaves—has received scant attention in howlers, a gap we fill in this study. We recorded diet, sequenced M/LWS opsin genes in four social groups of Alouatta palliata, and conducted colorimetric analysis of leaves consumed in Sector Santa Rosa, Costa Rica. For a majority of food species, including Ficus trees, an important resource year‐round, young leaves were more chromatically conspicuous from mature leaves to trichromatic than to hypothetical dichromatic phenotypes. We found that 18% of opsin genes were MWS/LWS hybrids; when combined with previous research, the incidence of hybrid M/LWS opsins in this species is 13%. In visual models of food discrimination ability, the hybrid trichromatic phenotype performed slightly poorer than normal trichromacy, but substantially better than dichromacy. Our results provide support for the folivory hypothesis of routine trichromacy. Similar ecological pressures, that is, the search for young, reddish leaves, may have driven the independent evolution of routine trichromacy in primates on separate continents. We discuss our results in the context of balancing selection acting on New World monkey opsin genes and hypothesize that howlers experience stronger selection against dichromatic phenotypes than other sympatric species, which rely more heavily on cryptic foods.     

Production of L-Tryptophan by Sulfonamide-resistant Mutants

Sulfaguanidine-resistant mutant S-225, derived from a tryptophan-producing 5-fluoro-tryptophan-resistant mutant of Brevibacterium flavum, accumulated 19 g/liter of L-tryptophan at maximum when cultured for 72 hr in a medium containing 13% glucose as carbon source, 1.8-fold higher than did the parent. Strain S-225 accumulated 17 g/liter of L-tryptophan in a medium containing 10% sucrose as carbon source (17% yield based on the sugar). It also accumulated 450 mg/liter of chorismate, an intermediate common to the biosyntheses of tryptophan and p-aminobenzoate. The accumulation was 1.7-fold higher than that by the parent, suggesting that the intracellular concentration of chorismate was increased through acquisition of the sulfaguanidine resistance. Sulfaguanidine-resistant mutants were also derived from a tryptophan-producing mutant of Corynebacterium glutamicum. The mutants showed 2.2-fold higher maximum tryptophan production than did the parent.