The p75 neurotrophin receptor is a central regulator of glioma invasion

The invasive nature of cancers in general, and malignant gliomas in particular, is a major clinical problem rendering tumors incurable by conventional therapies. Using a novel invasive glioma mouse model established by serial in vivo selection, we identified the p75 neurotrophin receptor (p75^NTR) as a critical regulator of glioma invasion. Through a series of functional, biochemical, and clinical studies, we found that p75^NTR dramatically enhanced migration and invasion of genetically distinct glioma and frequently exhibited robust expression in highly invasive glioblastoma patient specimens. Moreover, we found that p75^NTR-mediated invasion was neurotrophin dependent, resulting in the activation of downstream pathways and producing striking cytoskeletal changes of the invading cells. These results provide the first evidence for p75^NTR as a major contributor to the highly invasive nature of malignant gliomas and identify a novel therapeutic target.     

Acidophilic and acid-tolerant fungi and yeasts

Fungi have not been systematically studied from mines and mine drainage waters, even though they are often encountered there. This paper provides a key from literature sources and lists morphological characteristics and habitat information for the 81 fungal species that have been collected or identified in pH <4 environments.     

Gene therapy for established murine collagen-induced arthritis by local and systemic adenovirus-mediated delivery of interleukin-4

To determine whether IL-4 is therapeutic in treating established experimental arthritis, a recombinant adenovirus carrying the gene that encodes murine IL-4 (Ad-mIL-4) was used for periarticular injection into the ankle joints into mice with established collagen-induced arthritis (CIA). Periarticular injection of Ad-mIL-4 resulted in a reduction in the severity of arthritis and joint swelling compared with saline- and adenoviral control groups. Local expression of IL-4 also reduced macroscopic signs of joint inflammation and bone erosion. Moreover, injection of Ad-mIL-4 into the hind ankle joints resulted in a decrease in disease severity in the untreated front paws. Systemic delivery of murine IL-4 by intravenous injection of Ad-mIL-4 resulted in a significant reduction in the severity of early-stage arthritis.     

Determination of the structure of the Escherichia coli K100 capsular polysaccharide, cross-reactive with the capsule from type b Haemophilus influenzae

The structure of the Escherichia coli K100 capsular polysaccharide, cross-reactive with that from type b Haemophilus influenzae, was determined by using a combination of chemical and spectroscopic techniques. The structure of the K100 repeating unit was found to be----3)-beta-D-Ribf-(1----2)-D-ribitol-5-(PO4----. The K100 polysaccharide is thus identical in composition to, but different in linkage from, the H. influenzae type b capsular polysaccharide, which has beta-D-Ribf-(1----1)-D-ribitol linkages.     

Distribution of quinolizidine alkaloid types in nine Ormosia species (Leguminosae-Papilionoideae)

Quinolizidine alkaloids were surveyed in 22 plant samples, representing nineOrmosia species and up to five different plant parts per species, using combined gas chromatography and mass spectroscopy. The detected alkaloids were classified into 40 structural types. There was a remarkable degree of dissimilarity of alkaloid-type profiles between any two plant samples, including those obtained from the same species and even from a single tree. The similarity of alkaloid-type profiles among the studied samples varied between 0% and 79% (Jaccard similarity coefficient). Of chemotaxonomic interest was the finding of acosmine inO. isthmensis, which previously had been reported only from the related genusAcosmium. Furthermore, the alkaloid-type profile ofO. panamensis seeds was distinct from that of all other samples, supporting the hypothesis that this species is only distantly related to the other Latin AmericanOrmosia species.     

Role of brown bears (Ursus arctos) in the flow of marine nitrogen into a terrestrial ecosystem

We quantified the amount, spatial distribution, and importance of salmon (Oncorhynchus spp.)-derived nitrogen (N) by brown bears (Ursus arctos) on the Kenai Peninsula, Alaska. We tested and confirmed the hypothesis that the stable isotope signature (δ¹⁵N) of N in foliage of white spruce (Picea glauca) was inversely proportional to the distance from salmon-spawning streams (r=–0.99 and P<0.05 in two separate watersheds). Locations of radio-collared brown bears, relative to their distance from a stream, were highly correlated with δ¹⁵N depletion of foliage across the same gradient (r=–0.98 and –0.96 and P<0.05 in the same two separate watersheds). Mean rates of redistribution of salmon-derived N by adult female brown bears were 37.2±2.9 kg/year per bear (range 23.1–56.3), of which 96% (35.7±2.7 kg/year per bear) was excreted in urine, 3% (1.1±0.1 kg/year per bear) was excreted in feces, and <1% (0.3± 0.1 kg/year per bear) was retained in the body. On an area basis, salmon-N redistribution rates were as high as 5.1±0.7 mg/m² per year per bear within 500 m of the stream but dropped off greatly with increasing distance. We estimated that 15.5–17.8% of the total N in spruce foliage within 500 m of the stream was derived from salmon. Of that, bears had distributed 83–84%. Thus, brown bears can be an important vector of salmon-derived N into riparian ecosystems, but their effects are highly variable spatially and a function of bear density. Received: 11 February 1999 / Accepted: 7 July 1999     

Effects of Obesity and Body Fat Distribution on Lipids and Lipoproteins in Nondiabetic American Indians: The Strong Heart Study

Objectives: To examine the relationship between obesity and lipoprotein profiles and compare the effects of total obesity and central adiposity on lipids/lipoproteins in American Indians. Research Methods and Procedures: Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74 years participating in the Strong Heart Study. Total obesity was estimated using body mass index (BMI). Central obesity was measured as waist circumference. Lipoprotein measures included triglycerides, high‐density lipoprotei in (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, apolipoprotein AI (apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses were used to examine the associations between obesity and lipids/lipoproteins. Results: Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2 kg/m²) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m²), but there was no sex difference in waist circumference. Men had higher apoB and lower apoAI levels than did women. In women, when adjusted for center, gender, and age, BMI was significantly related to HDL cholesterol (r = ?0.24, p < 0.001). There was a significant but weak relation with apoAI (r = ?0.14 p < 0.001). Waist circumference was positively related to triglycerides (r = 0.14 p < 0.001) and negatively related to HDL cholesterol (r = ?0.23, p < 0.001) and apoAI (r = ?0.13, p < 0.001). In men, BMI was positively correlated with triglycerides (r = 0.30, p < 0.001) and negatively correlated with HDL cholesterol (r = ?0.35, p < 0.001) and apoAI (r = ?0.23, p < 0.001). Triglycerides increased with waist circumference (r = 0.30, p < 0.001) and HDL cholesterol decreased with waist circumference (r = ?0.36 p < 0.001). In both women and men there was an inverted U‐shaped relationship between obesity and waist with LDL cholesterol and apoB. In canonical correlation analysis, waist circumference received a greater weight (0.86) than did BMI (0.17) in women. However, the canonical weights were similar for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (?1.02) carried greater weight in women, whereas in men, triglycerides (0.50), and HDL cholesterol (?0.64) carried a large amount of weight. All the correlation coefficients between BMI, waist circumference, and the first canonical variable of lipids/lipoproteins or between the individual lipid/lipoprotein variables and the first canonical variable of obesity were smaller in women than in men. Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI and waist circumference in men. All lipid/lipoprotein changes in women in relation to BMI and waist circumference were minimal. Discussion: The main lipoprotein abnormality related to obesity in American Indians was decreased HDL cholesterol, especially in men. Central adiposity was more associated with abnormal lipid/lipoprotein profiles than general obesity in women; both were equally important in men.     

Molecular characterization of the thermosensitive E1 ubiquitin-activating enzyme cell mutant A31N-ts20. Requirements upon different levels of E1 for the ubiquitination/degradation of the various protein substrates in vivo.

According to our current knowledge, protein ubiquitination involves three steps: activation of ubiquitin through formation of an energy-rich bond with an E1 ubiquitin-activating enzyme; and transfer of activated ubiquitin onto E2 ubiquitin-conjugating enzymes, which, in turn, alone, or in combination with E3 ubiquitin-protein ligase enzymes, transfer ubiquitin onto target proteins. A31N-ts20 cells are mouse embryo fibroblasts, thermosensitive for E1. We show here that: (a) the enzymatic activity of the enzyme is heat-inactivatable in vitro; and (b) a major mechanism responsible for E1 inactivation in vivo consists of accelerated destruction. Surprisingly, a >90% reduction in E1 abundance little alters the formation of the bulk of protein-ubiquitin conjugates when A31N-ts20 cells are grown at the nonpermissive temperature, indicating that cautious interpretation of results is required when studying ubiquitination of specific substrates using this cell line. Surprisingly, our data also indicate that, in vivo, ubiquitination of the various protein substrates in A31N-ts20 cells requires different amounts of E1, indicating that this mutant cell line can be used for unveiling the existence of differences in the intimate mechanisms responsible for the ubiquitination of the various cell proteins in vivo, and for providing criteria of reliability when developing in vitro ubiquitination assays for specific proteins.