MMT, Npeoc-protected spermine, a valuable synthon for the solid phase synthesis of oligonucleotide oligospermine conjugates via guanidine linkers

Solid phase spermine oligomerization via guanidine linkers was achieved using activated thiourea coupling reaction with primary amino group. Disymmetric spermine synthon was efficiently synthesised in eight steps from spermine. MMT group was used as coupling monitor and resulting oligomeric spermines were conjugated to oligonucleotides.     

Interactions between natural killer cells and antibody Fc result in enhanced antibody neutralization of human immunodeficiency virus type 1

Antibodies can prevent lentivirus infections in animals and may play a role in controlling viral burden in established infection. In preventing and particularly in controlling infection, antibodies likely function in the presence of large quantities of virus. In this study, we explored the mechanisms by which antibodies neutralize large inocula of human immunodeficiency virus type 1 (HIV-1) on different target cells. Immunoglobulin G (IgG) from HIV-infected patients was tested for neutralizing activity against primary R5 strains of HIV-1 at inocula ranging from 100 to 20,000 50% tissue culture infective doses. At all virus inocula, inhibition by antibody was enhanced when target cells for virus growth were monocyte-depleted, peripheral blood mononuclear cells (PBMCs) rather than CD4(+) lymphocytes. However, enhanced inhibition on PBMCs was greatest with larger amounts of virus. Depleting PBMCs of natural killer (NK) cells, which express Fc receptors for IgG (FcgammaRs), abrogated the enhanced antibody inhibition, whereas adding NK cells to CD4(+) lymphocytes restored inhibition. There was no enhanced inhibition on PBMCs when F(ab')(2) was used. Further experiments demonstrated that the release of beta-chemokines, most likely through FcgammaR triggering of NK cells, contributed modestly to the antiviral activity of antibody on PBMCs and that antibody-coated virus adsorbed to uninfected cells provided a target for NK cell-mediated inhibition of HIV-1. These results indicate that Fc-FcgammaR interactions enhance the ability of antibody to neutralize HIV-1. Since FcgammaR-bearing cells are always present in vivo, FcgammaR-mediated antibody function may play a role in the ability of antibody to control lentivirus infection.     

A new entomopathogenic nematode, <Emphasis Type="Italic">Steinernema robustispiculum</Emphasis> n. sp. (Rhabditida: Steinernematidae), from Chumomray National Park in Vietnam

Steinernemar robustispiculum n. sp. (Rhabditida: Steinernematidae) was isolated from woodland in Chumomray National Park, Sason, Sathay, Kontum, Vietnam. Its morphology, morphometrics, cross-hybridisation and the ITS-rDNA sequence analysis revealed that S. robustispiculum clearly differs from other known Steinernema spp. As in the cases of S. intermedium (Poinar, 1985), S. robustispiculum has very robust spicules, but it can be distinguished by the longer tail of the infective juvenile, lower E%, shorter spicules, the shape of the spicules, the number of genital papillae in the caudal region and the presence of a mucron on the male tail. S. robustispiculum has a lateral field resembling that of S. sangi Phan, Nguyen & Moens, 2001, but can be distinguished by a higher E%, higher D%, smaller length to width ratio of the spicules and the morphology of both the spicule head (manubrium) and the dorsal lobe of the spicule. The morphometrics of infective juveniles of S. robustispiculum are similar to those of S. monticolum Stock, Choo & Kaya, 1997; these species can be distingusihed by the position of the excretory pore, the smaller length to width ratio of the spicules, and the length and morphology of the spicule head (manubrium). The phylogenetic relationships within Steinernema Travassos, 1927, including the newly sequenced Vietnamese species S. robustispiculum n. sp., S. loci Phan, Nguyen & Moens, 2001, S. thanhi Phan, Nguyen & Moens, 2001 and S. sangi, are presented based on analyses of the ITS-rDNA. The ITS RFLP profiles obtained from 17 different restriction enzymes are also presented.     

Lipin, a lipodystrophy and obesity gene

Lipodystrophy and obesity represent extreme and opposite ends of the adiposity spectrum and have typically been attributed to alterations in the expression or function of distinct sets of genes. We previously demonstrated that lipin deficiency impairs adipocyte differentiation and causes lipodystrophy in the mouse. Using two different tissue-specific lipin transgenic mouse strains, we now demonstrate that enhanced lipin expression in either adipose tissue or skeletal muscle promotes obesity. This occurs through diverse mechanisms in the two tissues, with lipin levels in adipose tissue influencing the fat storage capacity of the adipocyte, and lipin levels in skeletal muscle acting as a determinant of whole-body energy expenditure and fat utilization. Thus, variations in lipin levels alone are sufficient to induce extreme states of adiposity and may represent a mechanism by which adipose tissue and skeletal muscle modulate fat mass and energy balance.