Lysophosphatidic acid: A potential mediator of osteoblast–osteoclast signaling in bone

Osteoclasts (bone resorbing cells) and osteoblasts (bone forming cells) play essential roles in skeletal development, mineral homeostasis and bone remodeling. The actions of these two cell types are tightly coordinated, and imbalances in bone formation and resorption can result in disease states, such as osteoporosis. Lysophosphatidic acid (LPA) is a potent bioactive phospholipid that influences a number of cellular processes, including proliferation, survival and migration. LPA is also involved in wound healing and pathological conditions, such as tumor metastasis and autoimmune disorders. During trauma, activated platelets are likely a source of LPA in bone. Physiologically, osteoblasts themselves can also produce LPA, which in turn promotes osteogenesis. The capacity for local production of LPA, coupled with the proximity of osteoblasts and osteoclasts, leads to the intriguing possibility that LPA acts as a paracrine mediator of osteoblast–osteoclast signaling. Here we summarize emerging evidence that LPA enhances the differentiation of osteoclast precursors, and regulates the morphology, resorptive activity and survival of mature osteoclasts. These actions arise through stimulation of multiple LPA receptors and intracellular signaling pathways. Moreover, LPA is a potent mitogen implicated in promoting the metastasis of breast and ovarian tumors to bone. Thus, LPA released from osteoblasts is potentially an important autocrine and paracrine mediator — physiologically regulating skeletal development and remodeling, while contributing pathologically to metastatic bone disease. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.     

A systematic revision of Baconia Lewis (Coleoptera,?Histeridae,Exosternini)

Here we present a complete revision of the species of Baconia. Up until now there have been 27 species assigned to the genus (Mazur, 2011), in two subgenera (Binhister Cooman and Baconia s. str.), with species in the Neotropical, Nearctic, Palaearctic, and Oriental regions. We recognize all these species as valid and correctly assigned to the genus, and redescribe all of them. We synonymize Binhister, previously used for a polyphyletic assemblage of species with varied relationships in the genus. We move four species into Baconia from other genera, and describe 85 species as new, bringing the total for the genus to 116 species. We divide these into 12 informal species groups, leaving 13 species unplaced to group. We present keys and diagnoses for all species, as well as habitus photos and illustrations of male genitalia for nearly all. The genus now contains the following species and species groups: Baconia loricata group [Baconia loricata Lewis, 1885, B. patula Lewis, 1885, Baconia gounellei (Marseul, 1887a), Baconia jubaris (Lewis, 1901), Baconia festiva (Lewis, 1891), Baconia foliosoma sp. n., Baconia sapphirina sp. n., Baconia furtiva sp. n., Baconia pernix sp. n., Baconia applanatis sp. n., Baconia disciformis sp. n., Baconia nebulosa sp. n., Baconia brunnea sp. n.], Baconia godmani group [Baconia godmani (Lewis, 1888), Baconia venusta (J. E. LeConte, 1845), Baconia riehli (Marseul, 1862), comb. n., Baconia scintillans sp. n., Baconia isthmia sp. n., Baconia rossi sp. n., Baconia navarretei sp. n., Baconia maculata sp. n., Baconia deliberata sp. n., Baconia excelsa sp. n., Baconia violacea (Marseul, 1853), Baconia varicolor (Marseul, 1887b), Baconia dives (Marseul, 1862), Baconia eximia (Lewis, 1888), Baconia splendida sp. n., Baconia jacinta sp. n., Baconia prasina sp. n., Baconia opulenta sp. n., Baconia illustris (Lewis, 1900), Baconia choaspites (Lewis, 1901), Baconia lewisi Mazur, 1984], Baconia salobrus group [Baconia salobrus (Marseul, 1887b), Baconia turgifrons sp. n., Baconia crassa sp. n., Baconia anthracina sp. n., Baconia emarginata sp. n., Baconia obsoleta sp. n.], Baconia ruficauda group [Baconia ruficauda sp. n., Baconia repens sp. n.], Baconia angusta group [Baconia angusta Schmidt, 1893a, Baconia incognita sp. n., Baconia guartela sp. n., Baconia bullifrons sp. n., Baconia cavei sp. n., Baconia subtilis sp. n., Baconia dentipes sp. n., Baconia rubripennis sp. n., Baconia lunatifrons sp. n.], Baconia aeneomicans group [Baconia aeneomicans (Horn, 1873), Baconia pulchella sp. n., Baconia quercea sp. n., Baconia stephani sp. n., Baconia irinae sp. n., Baconia fornix sp. n., Baconia slipinskii Mazur, 1981, Baconia submetallica sp. n., Baconia diminua sp. n., Baconia rufescens sp. n., Baconia punctiventer sp. n., Baconia aulaea sp. n., Baconia mustax sp. n., Baconia plebeia sp. n., Baconia castanea sp. n., Baconia lescheni sp. n., Baconia oblonga sp. n., Baconia animata sp. n., Baconia teredina sp. n., Baconia chujoi (Cooman, 1941), Baconia barbarus (Cooman, 1934), Baconia reposita sp. n., Baconia kubani sp. n., Baconia wallacea sp. n., Baconia bigemina sp. n., Baconia adebratti sp. n., Baconia silvestris sp. n.], Baconia cylindrica group [Baconia cylindrica sp. n., Baconia chatzimanolisi sp. n.], Baconia gibbifer group [Baconia gibbifer sp. n., B. piluliformis sp. n., Baconia maquipucunae sp. n., Baconia tenuipes sp. n., Baconia tuberculifer sp. n., Baconia globosa sp. n.], Baconia insolita group [Baconia insolita (Schmidt, 1893a), comb. n., Baconia burmeisteri (Marseul, 1870), Baconia tricolor sp. n., Baconia pilicauda sp. n.], Baconia riouka group [Baconia riouka (Marseul, 1861), Baconia azuripennis sp. n.], Baconia famelica group [Baconia famelica sp. n., Baconia grossii sp. n., Baconia redemptor sp. n., Baconia fortis sp. n., Baconia longipes sp. n., Baconia katieae sp. n., Baconia cavifrons (Lewis, 1893), comb. n., Baconia haeterioides sp. n.], Baconia micans group [Baconia micans (Schmidt, 1889a), Baconia carinifrons sp. n., Baconia fulgida (Schmidt, 1889c)], Baconia incertae sedis [Baconia chilense (Redtenbacher, 1867), Baconia glauca (Marseul, 1884), Baconia coerulea (Bickhardt, 1917), Baconia angulifrons sp. n., Baconia sanguinea sp. n., Baconia viridimicans (Schmidt, 1893b), Baconia nayarita sp. n., Baconia viridis sp. n., Baconia purpurata sp. n., Baconia aenea sp. n., Baconia clemens sp. n., Baconia leivasi sp. n., Baconia atricolor sp. n.]. We designate lectotypes for the following species: Baconia loricata Lewis, 1885,Phelister gounellei Marseul, 1887, Baconia jubaris Lewis, 1901, Baconia festiva Lewis, 1891, Platysoma venustum J.E. LeConte, 1845, Phelister riehli Marseul, 1862, Phelister violaceus Marseul, 1853, Phelister varicolor Marseul, 1887b, Phelister illustris Lewis, 1900, Baconia choaspites Lewis, 1901, Epierus festivus Lewis, 1898, Phelister salobrus Marseul, 1887, Baconia angusta Schmidt, 1893a, Phelister insolitus Schmidt, 1893a, Pachycraerus burmeisteri Marseul, 1870, Phelister riouka Marseul, 1861, Homalopygus cavifrons Lewis, 1893, Phelister micans Schmidt, 1889a, Phelister coeruleus Bickhardt, 1917, and Phelister viridimicans Schmidt, 1893b. We designate neotypes for Baconia patula Lewis, 1885 and Hister aeneomicans Horn, 1873, whose type specimens are lost.     

Probing the structural determinants of yellow fluorescence of a protein from Phialidium sp

Fluorescent proteins homologous to green fluorescent protein (avGFP) display pronounced spectral variability due to different chromophore structures and variable chromophore interactions with the surrounding amino acids. To gain insight into the structural basis for yellow emission, the 3D structure of phiYFP (λ_em = 537 nm), a protein from the sea medusa Phialidium sp., was built by a combined homology modeling – mass spectrometry approach. Mass spectrometry of the isolated chromophore-bearing peptide reveals that the chromophore of phiYFP is chemically identical to that of avGFP (λ_em = 508 nm). The experimentally acquired chromophore structure was combined with the homology-based model of phiYFP, and the proposed 3D structure was used as a starting point for identification of the structural features responsible for yellow fluorescence. Mutagenesis of residues in the local chromophore environment of phiYFP suggests that multiple factors cooperate to establish the longest-wavelength emission maximum among fluorescent proteins with an unmodified GFP-like chromophore.     

Mycoplasma gallisepticum produces a histone-like protein that recognizes base mismatches in DNA

Mycoplasmas are the smallest known microorganisms, with drastically reduced genome sizes. One of the essential biochemical pathways lost in mycoplasmas is methylation-mediated DNA repair (MMR), which is responsible for correction of base substitutions, insertions, and deletions in both bacteria and higher organisms. We found that the histone-like protein encoded by the himA/hup_2 gene of Mycoplasma gallisepticum (mgHU) recognizes typical MMR substrates, in contrast to homologues from other species. The recognition of substitution mismatches is sequence-dependent, with affinities decreasing in the following order: CC > CT = TT > AA = AC. Insertions or deletions of one nucleotide are also specifically recognized with the following sequence-dependent preference: A = T > C. One-nucleotide lesions involving guanine are bound only weakly, and this binding is indistinguishable from binding to intact DNA. Although mgHU is dissimilar to Escherichia coli HU, expression in a slow-growing hupAB E. coli strain restores wild-type growth. The results indicate that mgHU executes all essential functions of bacterial architectural proteins. The origin and the possible role of enhanced specificity for typical MMR substrates are discussed.     

Replacement of C-terminal histidines uncouples membrane insertion and translocation in diphtheria toxin T-domain

The translocation (T) domain plays a key role in the action of diphtheria toxin and is responsible for transferring the N-terminus-attached catalytic domain across the endosomal membrane into the cytosol in response to acidification. The T-domain undergoes a series of pH-triggered conformational changes that take place in solution and on the membrane interface, and ultimately result in transbilayer insertion and N-terminus translocation. Structure-function studies along this pathway have been hindered because the protein population occupies multiple conformations at the same time. Here we report that replacement of the three C-terminal histidine residues, H322, H323, and H372, in triple-R or triple-Q mutants prevents effective translocation of the N-terminus. Introduction of these mutations in the full-length toxin results in decrease of its potency. In the context of isolated T-domain, these mutations cause loss of characteristic conductance in planar bilayers. Surprisingly, these mutations do not affect general folding in solution, protein interaction with the membranes, insertion of the consensus transmembrane helical hairpin TH8-9, or the ability of the T-domain to destabilize vesicles to cause leakage of fluorescent markers. Thus, the C-terminal histidine residues are critical for the transition from the inserted intermediate state to the open-channel state in the insertion/translocation pathway of the T-domain.     

A missense mutation in DHDDS, encoding dehydrodolichyl diphosphate synthase, is associated with autosomal-recessive retinitis pigmentosa in Ashkenazi Jews

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations caused by mutations in at least 50 genes. Using homozygosity mapping in Ashkenazi Jewish (AJ) patients with autosomal-recessive RP (arRP), we identified a shared 1.7 Mb homozygous region on chromosome 1p36.11. Sequence analysis revealed a founder homozygous missense mutation, c.124A>G (p.Lys42Glu), in the dehydrodolichyl diphosphate synthase gene (DHDDS) in 20 AJ patients with RP of 15 unrelated families. The mutation was not identified in an additional set of 109 AJ patients with RP, in 20 AJ patients with other inherited retinal diseases, or in 70 patients with retinal degeneration of other ethnic origins. The mutation was found heterozygously in 1 out of 322 ethnically matched normal control individuals. RT-PCR analysis in 21 human tissues revealed ubiquitous expression of DHDDS. Immunohistochemical analysis of the human retina with anti-DHDDS antibodies revealed intense labeling of the cone and rod photoreceptor inner segments. Clinical manifestations of patients who are homozygous for the c.124A>G mutation were within the spectrum associated with arRP. Most patients had symptoms of night and peripheral vision loss, nondetectable electroretinographic responses, constriction of visual fields, and funduscopic hallmarks of retinal degeneration. DHDDS is a key enzyme in the pathway of dolichol, which plays an important role in N-glycosylation of many glycoproteins, including rhodopsin. Our results support a pivotal role of DHDDS in retinal function and may allow for new therapeutic interventions for RP.     

Synthesis, crystal structure and characterization of alkali metal hydroxoantimonates

Several alkali metal hydroxoantimonates, K₂[Sb(O)(OH)₅], Na[Sb(OH)₆], Cs[Sb(OH)₆] and Cs₂[Sb₂(μ-O)₂(OH)₈] were isolated from aqueous solutions and characterized by single crystal and powder X-ray diffraction studies and by FTIR and thermal analysis. Crystal structures involving [Sb(O)(OH)₅]²⁻ were never anticipated before, and this is also the first disclosure of a dinuclear antimonate [Sb₂(μ-O)₂(OH)₈]²⁻. Aqueous antimonate solutions of different pH were studied by high resolution electrospray mass spectrometry showing pH indifferent spectra and predominance of the mono and dinuclear antimonate species at pH 4-10.     

Synthesis of five nona-β-(1→6)-d-glucosamines with various patterns of N-acetylation corresponding to the fragments of exopolysaccharide of Staphylococcus aureus

A series of five 3-acetamidopropyl β-glycosides of nona-β-(1→6)-glucosamines containing two N-acetylglucosamine residues separated by a different number of glucosamine units with free amino groups have been synthesized using a convergent blockwise approach. Oxazoline glycosylation was used to introduce N-acetylglucosamine residues. These nonasaccharides are structurally related to the poly-N-acetylglucosamine (PNAG) extracellular polysaccharide of Staphylococcus aureus and can be used as models for biochemical and immunological studies.