Primate molecular phylogenetics in a genomic era

A primary objective of molecular phylogenetics is to use molecular data to elucidate the evolutionary history of living organisms. Dr. Morris Goodman founded the journal Molecular Phylogenetics and Evolution as a forum where scientists could further our knowledge about the tree of life, and he recognized that the inference of species trees is a first and fundamental step to addressing many important evolutionary questions. In particular, Dr. Goodman was interested in obtaining a complete picture of the primate species tree in order to provide an evolutionary context for the study of human adaptations. A number of recent studies use multi-locus datasets to infer well-resolved and well-supported primate phylogenetic trees using consensus approaches (e.g., supermatrices). It is therefore tempting to assume that we have a complete picture of the primate tree, especially above the species level. However, recent theoretical and empirical work in the field of molecular phylogenetics demonstrates that consensus methods might provide a false sense of support at certain nodes. In this brief review we discuss the current state of primate molecular phylogenetics and highlight the importance of exploring the use of coalescent-based analyses that have the potential to better utilize information contained in multi-locus data.     

Prenylhydroxybenzoic acid compounds with pungent activity from Piper arieianum (CDC) leaves

Prenylhydroxybenzoic acid derivatives and other two analogues previously reported were isolated from Piper arieianum leaves. The structures of the compounds were assigned from detailed spectroscopical analysis (NMR 1D and 2D and HR ESI TOF MS) data and by comparison with data from the literature. These molecules posses pungent activity different to that of capsaicin and their activity is related to their structure and their mechanism of action can involve interactions with TRPV1 channel.     

Erratum: TMOF‐like factor controls the biosynthesis of serine proteases in the larval gut of Heliothis virescens

In our recently published paper, we the authors have found that in Table 3 there was a mistake in the statistical analysis of injected and control animals; they are not statistically different. Because of this faulty analysis, we initially did not find it necessary to include the 72 hour results that are highly statistically different. The amended Table 3 and the original article’s title page appear below.     

A comprehensive analysis of the geranylgeranylglyceryl phosphate synthase enzyme family identifies novel members and reveals mechanisms of substrate specificity and quaternary structure organization

Geranylgeranylglyceryl phosphate synthase (GGGPS) family enzymes catalyse the formation of an ether bond between glycerol‐1‐phosphate and polyprenyl diphosphates. They are essential for the biosynthesis of archaeal membrane lipids, but also occur in bacterial species, albeit with unknown physiological function. It has been known that there exist two phylogenetic groups (I and II) of GGGPS family enzymes, but a comprehensive study has been missing. We therefore visualized the variability within the family by applying a sequence similarity network, and biochemically characterized 17 representative GGGPS family enzymes regarding their catalytic activities and substrate specificities. Moreover, we present the first crystal structures of group II archaeal and bacterial enzymes. Our analysis revealed that the previously uncharacterized bacterial enzymes from group II have GGGPS activity like the archaeal enzymes and differ from the bacterial group I enzymes that are heptaprenylglyceryl phosphate synthases. The length of the isoprenoid substrate is determined in group II GGGPS enzymes by ‘limiter residues’ that are different from those in group I enzymes, as shown by site‐directed mutagenesis. Most of the group II enzymes form hexamers. We could disrupt these hexamers to stable and catalytically active dimers by mutating a single amino acid that acts as an ‘aromatic anchor’.     

Steroids from the root extract of Pentalinon andrieuxii

Two pregnane derivatives (1 and 2) were isolated from the methanolic root extract of Pentalinon andrieuxii, a plant used commonly in Yucatecan traditional medicine to treat leishmaniasis. The structures of both metabolites were established using spectroscopic methods and chemical correlation reactions. An X-ray structure of 1 is reported.     

Affinity of 3-acyl substituted 4-quinolones at the benzodiazepine site of GABA(A) receptors

The finding that alkyl 1,4-dihydro-4-oxoquinoline-3-carboxylate and N-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxamide derivatives may be high-affinity ligands at the benzodiazepine binding site of the GABA(A) receptor, prompted a study of 3-acyl-1,4-dihydro-4-oxoquinoline (3-acyl-4-quinolones). In general, the affinity of the 3-acyl derivatives was found to be comparable with the 3-carboxylate and the 3-carboxamide derivatives, and certain substituents (e.g., benzyl) in position 6 were again shown to be important. As it is believed that the benzodiazepine binding site is situated between an alpha- and a gamma-subunit in the GABA(A) receptor, selected compounds were tested on the alpha(1)beta(2)gamma(2s), alpha(2)beta(2)gamma(2s) and alpha(3)beta(2)gamma(2s) GABA(A) receptor subtypes. The 3-acyl-4-quinolones display various degrees of selectivity for alpha(1)- versus alpha(2)- and alpha(3)-containing receptors, and high-affinity ligands essentially selective for alpha(1) over alpha(3) were developed.     

Imidazo[1,2-a]pyridine derivatives as inhibitors of TNF-alpha expression in T cells

Novel hexahydroimidazo[1,2-a]pyridines prepared by the addition of ethyl (1-benzylimidazolidin-2-ylidene)acetate (2) to the fungal metabolite podoscyphic acid (1a) and esters of 1a have been evaluated for their ability to inhibit the inducible TNF-alpha promoter activity in T cells. The methyl ester 3b is the most potent, inhibiting the TNF-alpha driven reporter gene expression in Jurkat T cells with an IC(50)-value of 2.0 microg/ml (3.6 microM). In addition, compound 3b inhibited the inducible TNF-alpha production in the myelomonocytic U937 cells with an IC(50)-value of 4.6 microM.     

SAR studies of capsazepinoid bronchodilators 3: The thiourea part (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (C-region)

Certain derivatives and analogues of capsazepine are potent in vitro inhibitors of bronchoconstriction in human small airways. During an investigation of the dependency of the potency on the structural features of the capsazepinoids in the thiourea moiety (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (C-region), it was revealed that capsazepinoids with a thiourea or an amide link between the B-ring and the C-region in general have a good bronchorelaxing activity, while urea is a less attractive choice. Further, it was shown that 1,2,3,4-tetrahydroisoquinolines with a 2-(phenyl)ethyl derivative as the C-region are considerably more potent than those with an octyl group, while 2,3,4,5-tetrahydro-1H-2-benzazepines were found to be more insensitive to the nature of the C-region.     

Two chromones from Peperomia vulcanica

Two chromones: 5-hydroxy-2-(14′-(E)-nonadecenyl) chromone (1) and 5-hydroxy-2-[12′-(3″,4″-methylenedioxyphenyl)dodecanyl] chromone (2), together with six known compounds have been isolated from Peperomia vulcanica Baker & C. H. Wright (Piperaceae). Their structures were determined by spectroscopic analysis including 2D NMR techniques.