Primate-specific evolution of an LDLR enhancer

Background  

Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain.     

Weather indices for designing micro-insurance products for small-holder farmers in the tropics

Agriculture is inherently risky. Drought is a particularly troublesome hazard that has a documented adverse impact on agricultural development. A long history of decision-support tools have been developed to try and help farmers or policy makers manage risk. We offer site-specific drought insurance methodology as a significant addition to this process. Drought insurance works by encapsulating the best available scientific estimate of drought probability and severity at a site within a single number- the insurance premium, which is offered by insurers to insurable parties in a transparent risk-sharing agreement. The proposed method is demonstrated in a case study for dry beans in Nicaragua.     

Biohydrogen production by <Emphasis Type="Italic">Enterobacter cloacae</Emphasis> and <Emphasis Type="Italic">Citrobacter freundii</Emphasis> in carrier induced granules

Carrier induced granular particles comprising Enterobacter cloacae and Citrobacter freundii were used to generate H₂ from sucrose in an anaerobic fluidized bed bioreactor. At a hydraulic retention time of 4.5 h, 95.8% of the sucrose was consumed and the rate of H₂ production reached 180 mmol H₂ l h⁻¹. Biogas composition for H₂ and CO₂ was 42 and 55%, respectively. Alex von Holy—Deceased     

Novel fluorinated acridone derivatives. Part 1: synthesis and evaluation as potential anticancer agents

We report on the synthesis of a novel series of fluorinated acridones from 5-trifluoromethyl-1,3-cyclohexanedione. The cytotoxic activities of the compounds were studied in several cancer cells. Compounds 9a, 9c, 9e, 9f, and 9h exhibited significant anticancer activities in selected cell lines. Compound 9c is the most active showing GI₅₀ that ranged in values from 0.13 to 26 μM, covering a wide range of cancer cell lines.     

Effects of proximate cholesterol precursors and steroid hormones on mouse myeloma growth in serum-free medium

Summary The proximate cholesterol precursors lathosterol, 7-dehydrocholesterol and desmosterol supported the growth of NS-1 and X63 mouse myeloma cells. These cells and X63.653 cells are cholesterol auxotrophs, yet each was able to convert [³H]lathosterol to [³H]cholesterol. These results are consistent with the conclusion that cholesterol auxotrophy in these myeloma cells is due to a deficiency in 3-ketosteroid reductase activity. The steroid hormones testosterone, progesserone and hydrocortisone could not replace cholesterol as a medium supplement. These results provide a greater understanding of the cholesterol auxotrophy characteristic of cell lines clonally-derived from the MOPC 21 myeloma tumor, and they provide a rational basis for the use of sterols in defined culture medium for mouse myeloma cells. This work was supported by National Institute of Health grants CA40294 and CA37589 to G. H. Sato and by a grant from RJR nabisco Inc. Editor's Statement These results help identify the defect in myeloma cells leading to cholesterol auxotrophy. The use of these cells in hybridoma derivation adds practical utility to a detailed appreciation of cholesterol metabolism in these cultures.     

Preliminary crystallographic study of C-reactive protein from Limulus polyphemus

Crystals of C-reactive protein from Limulus polyphemus have been grown both with and without calcium. The space group for the calcium-free crystals is I422 or I4(1)22, and the cell parameters are a = b = 173.33 (4) A, c = 98.81 (3) A. The crystals diffract to at least 2.8 A resolution and are suitable for detailed structural studies.     

Survial of fasted rats exposed to altitude.

Rats fasted for 48-96h before exposure were shown to have a longer survival time at groups 33,500 ft (1 ft = 0.305 m) simulated altitude than nonfasted controls. Although both become hypothermic at 33500 ft, colonic temperatures of the fasted rats were not sufficiently lower than those of nonfasted animals to explain the difference in survival time. The injection of glucose and insulin before exposure almost completely eliminated the protection afforded by fasting, whereas glucose alone had no effect on survival. It is therefore suggested that an alteration in carbohydrate metabolism, possibly in combination with other starvation-induced changes, allowed fasted rats to survive at 33500 ft until declining body temperature reduced metabolic rate to a level compatible with oxygen supply.     

Glycosylation of Ceramide Potentiates Cellular Resistance to Tumor Necrosis Factor-α-Induced Apoptosis

Ceramide, as a second messenger, initiates one of the major signal transduction pathways in tumor necrosis factor-α (TNF-α)-induced apoptosis. Glucosylceramide synthase (GCS) catalyzes glycosylation of ceramide and produces glucosylceramide. By introduction of the GCS gene, cytotoxic resistance to TNF-α has been conferred in human breast cancer cells. MCF-7/GCS-transfected cells expressed 4.1-fold higher levels of GCS activity and exhibited a 15-fold (P < 0.0005) greater EC₅₀ for TNF-α, compared with the parental MCF-7 cell line. DNA fragmentation and DNA synthesis studies showed that TNF-α had little influence on the induction of apoptosis or on growth arrest in MCF-7/GCS cells, compared to MCF-7 cells. These studies reveal that TNF-α resistance in MCF-7/GCS cells is closely related to ceramide hyperglycosylation, a hallmark of this transfected cell line, and resistance was not aligned with changes in TNF receptor 1 expression. This work demonstrates that GCS, which catalyzes ceramide glycosylation, potentiates cytotoxic resistance to TNF-α.