La Traca : semanari pa la gent de tro: Año III Número 96 - 3 octubre 1886

Recurso electrónico. Valencia: BVNP, 2014

Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes

Substance P (SP) is a potent modulator of neuroimmunoregulation. We recently reported that human immune cells express SP and its receptor. We have now investigated the possible role that SP and its receptor plays in HIV infection of human mononuclear phagocytes. SP enhanced HIV replication in human blood-isolated mononuclear phagocytes, whereas the nonpeptide SP antagonist (CP-96,345) potently inhibited HIV infectivity of these cells in a concentration-dependent fashion. CP-96,345 prevented the formation of typical giant syncytia induced by HIV Bal strain replication in these cells. This inhibitory effect of CP-96,345 was because of the antagonism of neurokinin-1 receptor, a primary SP receptor. Both CP-96,345 and anti-SP antibody inhibited SP-enhanced HIV replication in monocyte-derived macrophages (MDM). Among HIV strains tested (both prototype and primary isolates), only the R5 strains (Bal, ADA, BL-6, and CSF-6) that use the CCR5 coreceptor for entry into MDM were significantly inhibited by CP-96,345; in contrast, the X4 strain (UG024), which uses CXCR4 as its coreceptor, was not inhibited. In addition, the M-tropic ADA (CCR5-dependent)-pseudotyped HIV infection of MDM was markedly inhibited by CP-96,345, whereas murine leukemia virus-pseudotyped HIV was not affected, indicating that the major effect of CP-96,345 is regulated by Env-determined early events in HIV infection of MDM. CP-96,345 significantly down-regulated CCR5 expression in MDM at both protein and mRNA levels. Thus, SP–neurokinin-1 receptor interaction may play an important role in the regulation of CCR5 expression in MDM, affecting the R5 HIV strain infection of MDM.

Physical properties and bulk organic geochemical results for sediments from DSDP Hole 96-619

The concentration and carbon isotopic composition (d13C) of sedimentary organic carbon (C_org), N/C ratios, and terrigenous and marine d13C_org endmembers form a basis from which to address problems of Late Quaternary glacial-interglacial climatic variability in a 208.7 m hydraulic piston core (DSDP 619) from the Pigmy Basin in the northern Gulf of Mexico. While interpretations of sedimentary d13C_org time series records are often not unique, paired analyses of d13C_org and N/C are consistent with the hypothesis that the C_org in the Pigmy Basin is a climatically determined mixture of C3-photosynthetic terrigenous and marine organic matter, confirming the earlier d13C_org model of Sackett (1964). A high resolution (~1.4-2.9 Ka/sample) d13C_org record shows that sedimentary organic carbon in interglacial oxygen isotope (sub)stages 1 and 5a-b are enriched in 13C (average +/-1 sigma values are -24.2+/-1.2? and -22.9+/-0.7? relative to PDB, respectively) while glacial isotope stage values 2 are relatively depleted (-25.6+/-0.5?). Concentrations of terrigenous and marine sedimentary organic carbon are calculated for the first time using d13C_org and C_org measurements, and empirically determined terrigenous and marine d13C_org endmembers. The net accumulation rate of terrigenous organic carbon is 4.3+/-2.6 times higher in isotope stages 2-4 than in (sub)stages 1 and 5a-b, recording higher erosion rates of terrigenous organic material in glacial times. The concentration and net accumulation rates of marine and terrigenous C_org suggest that the nutrient-bearing plume of the Mississippi River may have advanced and retreated across the Pigmy Basin as sea level fell and rose in response to glacial-interglacial sea level change.

Concentrations of interstitial water, methane, and other sediment components related to microorganisms at DSDP Holes 96-618 and 96-619

Radiolabeled products were formed from labeled substrates during anaerobic incubation of sediments from Sites 618, 619, and 622. One set of experiments formed 14CO2, 14CH4, and 35SH2 from 2-14C-acetate and 35S-sulfate; a second set formed 14CH4 from 14C-methylamine or 14C-trimethylamine. Levels of 14CO2 and 35S2 formed were two to three orders of magnitude greater than 14CH4. Production of 14CH4 by Deep Sea Drilling Project (DSDP) sediments was four to five orders of magnitude less than that formed by anoxic San Francisco Bay sediment. However, incubation of Site 622 sediment slurries under H2 demonstrated production of small quantities of CH4. These results indicate that DSDP sediments recovered from 4 to 167 m sub-bottom (age 85,000-110,000 yr.) harbor potential microbial activity which includes sulfate reducers and methanogens. Analysis of pore waters from these DSDP sites indicates that bacterial substrates (acetate, methylated amines) were present.