The use of oxadiazole and triazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 1: Establishing the pharmacophore

A series of HIV-1 integrase inhibitors containing a novel metal binding motif consisting of the 8-hydroxy-1,6-naphthyridine core and either an oxadiazole or triazole has been identified. The design of the key structural components was based on a two-metal coordination pharmacophore. This report presents initial structure–activity data that shows the new chelation architecture delivers potent inhibition in both enzymatic and antiviral assays.     

Living on the edge: life‐history of olive baboons at Gashaka‐Gumti National Park,Nigeria

Baboons are the most successful and ubiquitous African primates, renowned for their behavioral and reproductive flexibility, which enable them to inhabit a wide variety of habitat types. Owing to a number of long‐term field studies, comparative behavioral, developmental, demographic, and life‐history data are available from several populations, but study sites show a heavy bias toward South and East African savannahs, with little research in West or Central Africa. Life‐history data from such areas are important if we are fully to understand the nature of the environmental factors that limit baboon distribution. Here, we present demographic data for olive baboons at Gashaka‐Gumti National Park (GGNP), Nigeria, collected from December 2000–February 2006, and use these data to test comparative models of baboon life‐history. The GGNP habitat, which includes large areas of rainforest, is an environment in which baboons are little studied, and rainfall is much higher than at previous study sites. GGNP troop size data are presented from censuses, as well as life‐history data for two troops, one of which is within the park and wild‐feeding (Kwano troop), whereas the other dwells at the park edge, and supplements its diet by crop‐raiding (Gamgam troop). Troop sizes at GGNP are small compared with other field sites, but fit within previously suggested ranges for baboons under these climatic conditions. Inter‐birth intervals in Kwano troop were long compared with most studied populations, and values were not as predicted by comparative models. Consistent with known effects of food enhancement, Gamgam troop experienced shorter inter‐birth intervals and lower infant mortality than Kwano troop. We indicate some possible factors that exclude baboons from true rainforest, and suggest that the clearing of forests in Central and West Africa for agricultural land may allow baboons to extend their range into regions from which they are currently excluded. Am. J. Primatol. 71:293–304, 2009. © 2009 Wiley‐Liss, Inc.     

Nanoantenna-Enhanced Radiative and Anisotropic Decay Rates in Monolayer-Quantum Dots

Plasmonics - Nanoantenna-enhanced ultrafast emission from colloidal quantum dots as quantum emitters is required for fast quantum communications. On-chip integration of such devices requires a...     

Rosette-type tegumental glands associated with aesthetasc sensilla in the olfactory organ of the Caribbean spiny lobster, Panulirus argus

The lateral antennular flagellum of decapod crustaceans bears unique olfactory sensilla, namely the aesthetascs, and other sensilla types. In this study, we identify a new major tissue in the lateral flagellum of the Caribbean spiny lobster, Panulirus argus, namely “aesthetasc tegumental glands” (ATGs), based on immunostaining with antibodies against CUB serine protease (Csp), in situ hybridization with csp-specific probes, labeling with the F-actin marker phalloidin, labeling with the nuclear marker Hoechst 33258, and staining with methylene blue. Each ATG has 12–20 secretory cells arranged in a rosette. Each secretory cell has a Csp-immunoreactive basal portion and an apical portion containing granular material (metachromatic staining indicative of acid mucopolysaccharides). At the center of each secretory rosette is a phalloidin-positive common locus that gives rise to a main drainage duct projecting toward the cuticle. Scanning electron and light microscopy show that thin ducts traverse the cuticle and connect to “peg pores” proximal to the bases of the aesthetascs, with 3.4 peg pores per aesthetasc. Since the number of common loci is correlated with the number of peg pores, we conclude that each pore represents the outlet of one ATG, and that the secretions are released from them. We conclude further that ATGs and aesthetascs are functionally linked. We hypothesize that ATG secretions have antifouling and/or friction-reducing properties, and that they are spread over the surface of the aesthetascs by antennular grooming. A review of the literature suggests that ATGs are common in decapod crustacean antennules, and that rosette glands and grooming might be functionally coupled in other body areas.This study was supported by NSF IBN 0077474 and NIH DC00312.     

Mutations altering the cleavage specificity of a homing endonuclease

The homing endonuclease I-CreI recognizes and cleaves a particular 22 bp DNA sequence. The crystal structure of I-CreI bound to homing site DNA has previously been determined, leading to a number of predictions about specific protein–DNA contacts. We test these predictions by analyzing a set of endonuclease mutants and a complementary set of homing site mutants. We find evidence that all structurally predicted I-CreI/DNA contacts contribute to DNA recognition and show that these contacts differ greatly in terms of their relative importance. We also describe the isolation of a collection of altered specificity I-CreI derivatives. The in vitro DNA-binding and cleavage properties of two such endonucleases demonstrate that our genetic approach is effective in identifying homing endonucleases that recognize and cleave novel target sequences.     

Comparison of the cytotoxic response against ovarian cancer by immune effector cells isolated and expanded from normal donors and ovarian cancer patients

Background/AimsThe aim of this study was to compare the cytotoxic response against ovarian cancer (OC) cells elicited by different immune effector cells in combination with the cytokines interleukin (IL)-2 and interferon (IFN) α-2b.MethodsOC cells were co-cultured with peripheral blood mononuclear cells (PBMC) from normal donors or OC patients and IL-2 or IFN α-2b alone or in combination, in order to determine the cytotoxicity. T cells were isolated from healthy donors to determine T cell cytotoxic activity. PBMC from healthy donors and OC patients were expanded in an IL-2/IL-7/IL-12 cocktail with and without anti-CD3 antibody, and the cytotoxic activity measured. Flow cytometry was performed on primary, selected and expanded cells to determine T, B, and natural killer- (NK) cell percentages.ResultsHealthy donor PBMC elicited a significant cytotoxic response (59%) compared with OC patient PBMC (7%). T cells enriched from normal donors elicited a significant cytotoxic response (18%) compared with controls lacking effector cells (1.4%); however, the cytotoxicity observed was significantly less compared with unselected PBMC. Expanded effector cells consisted primarily of T cells (98%) and the fold-expansion was significantly higher in the presence of anti-CD3 (19- versus 132-fold). No significant difference in the expansion (either fold-expansion or cell type) was observed between OC patients and healthy donors. Expanded cells from both healthy donors and OC patients elicited a significant cytotoxic response in the presence of IL-2 (19% and 22%) compared with controls.ConclusionsPBMC from OC patients do not elicit a significant cytotoxic response; however, ex vivo-expanded cells from OC patients are capable of cytotoxic killing similar to unexpanded T cells isolated from normal donors. These data provide the groundwork for further development of cellular therapy against OC.     

Fructose production by Zymomonas mobilis in fed-batch culture with minimal sorbitol formation

Summary Fed-batch cultures of Zymomonas mobilis (UQM 2864), a mutant unable to metabolise fructose, grown on diluted sugar cane syrup (200 g/l sucrose) achieved yields of 90.5 g/l fructose and 48.3 g/l ethanol with minimal sorbitol formation and complete utilization of the substrate. The effect of inoculum size on sorbitol formation in the batch stage of fed-batch fermentation are reported. Fermentation of sucrose (350 g/l) supplemented with nutrients yielded 142 g/l fructose and 76.5 g/l ethanol. Some fructose product loss at high fructose concentrations was observed. The fed-batch fermentation process offers a method for obtaining high concentrations of fructose and ethanol from sucrose materials.