The Effect of Luteolin on Human Glioblastoma

Glioblastoma multiforme (GBM) is widely recognized as the most common and lethal of the malignant gliomas. Few effective therapeutic treatments are available as five-year survival rates of diagnosed individuals are less than five percent. Luteolin, a common flavonoid found in a variety of fruits and vegetables, has demonstrated significant promise in combating cancers of the breast, colon, liver, lung, and bone. In this study, we investigated the effects of luteolin on glioblastoma multiforme cell lines U-251, U-87, and U-1242. Cell viability was assessed using cell count with trypan blue exclusion and MTT assays. Results revealed that luteolin reduces GBM cell viability and cell proliferation in a time and concentration-dependent manner. Western Blot analysis indicated that luteolin decreased AKT, ERK, and MAPK phosphorylation following treatment with EGF. Additionally, luteolin promoted apoptosis in GBM cells by inducing PARP and caspase-3 cleavage, and decreasing levels of the anti-apoptotic protein BCL-XL. Our results indicate that luteolin exhibits a biological effect and may be used as a therapeutic agent for glioblastoma multiforme

Soybean seed protein, oil, fatty acids, and mineral composition as influenced by soybean-corn rotation

Effects of crop rotation on soybean (Glycine max (L) Merr.) seed composition have not been well investigated. Therefore, the objective of this study was to investigate the effects of soybean-corn (Zea mays L.) rotations on seed protein, oil, and fatty acids composition on soybean. Soybeans were grown at Stoneville, MS, from 2005 to 2008 in five different scheduled cropping sequences. In 2007, following three years of rotation with corn, seed oleic acid percentage was significantly higher in any crop rotation than continuous soybean. The increase of oleic fatty acid ranged from 61 to 68% in 2007, and from 27 to 51% in 2008, depending on the rotation. The increase of oleic acid was accompanied by significant increases in seed concentrations of phosphorus (P), iron (Fe), and boron (B). In 2007, the increase of P ranged from 60 to 75%, Fe from 70 to 72%, and B from 34 to 69%. In 2008, the increase of P ranged from 82 to 106%, Fe from 32 to 84%, and B from 62 to 77%. Continuous soybean had higher linoleic:oleic ratio and linoleic: palmitic + stearic + oleic ratio, indicating that relative quantity of linoleic acid decreased in rotated crops. The total production of protein, oil, stearic and oleic fatty acids was the lowest in continuous soybean. The total production of palmitic acid was inconsistent across years. The results show that soybean- corn rotation affects seed composition by consistently increasing seed oleic fatty acid, P, Fe, and B concentrations. Higher oleic acid, unsaturated fatty acid, is desirable for oil stability and long-shelf storage. The mechanisms of how these nutrients are involved are not yet understood

Emergency Department Crowding: Factors Influencing Flow

Background: The objective of this study was to evaluate those factors, both intrinsic and extrinsic to the emergency department (ED) that influence two specific components of throughput: “door-to-doctor” time and dwell time.Methods: We used a prospective observational study design to determine the variables that played a significant role in determining ED flow. All adult patients seen or waiting to be seen in the ED were observed at 8pm (Monday-Friday) during a three-month period. Variables measured included daily ED volume, patient acuity, staffing, ED occupancy, daily admissions, ED boarder volume, hospital volume, and intensive care unit volume. Both log-rank tests and time-to-wait (survival) proportional-hazard regression models were fitted to determine which variables were most significant in predicting “door-to-doctor” and dwell times, with full account of the censoring for some patients.Results: We captured 1,543 patients during our study period, representing 27% of total daily volume. The ED operated at an average of 85% capacity (61-102%) with an average of 27% boarding. Median “door-to-doctor” time was 1.8 hours, with the biggest influence being triage category, day of the week, and ED occupancy. Median dwell time was 5.5 hours with similar variable influences.Conclusion: The largest contributors to decreased patient flow through the ED at our institution were triage category, ED occupancy, and day of the week. Although the statistically significant factors influencing patient throughput at our institution involve problems with inflow, an increase in ED occupancy could be due to substantial outflow obstruction and may indicate the necessity for increased capacity both within the ED and hospital. [West J Emerg Med. 2010; 11(1):10-15

Measuring search-engine quality and query difficulty: Ranking with target and freestyle

Instead of using traditional performance measures such as precision and recall, information retrieval performance may be measured by considering the probability that the search engine is optimal and the difficulty associated with retrieving documents with a given query or on a given topic. These measures of desirable characteristics are more easily and more directly interpretable than are traditional measures. The performance of the Target and Freestyle search engines is examined and is very good. Each query in the CF database is assigned a difficulty number, and these numbers are found to strongly correlate with other measures of retrieval performance such as an E or F value. The query difficulty correlates weakly with query length

Pubertal timing and breast density in young women: a prospective cohort study.

BACKGROUND:Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. METHODS:From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. RESULTS:The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)). CONCLUSIONS:Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk

Xenon isotopes in Archean and Proterozoic insoluble organic matter: a robust indicator of syngenecity?

Insoluble organic materials (kerogens) isolated from ancient sedimentary rocks provide unique insights into the evolution of early life. However, establishing whether these kerogens are indeed syngenetic with the deposition of associated sedimentary host rocks, or contain contribution from episodes of secondary deposition, is not straightforward. Novel geochemical criterions are therefore required to test the syngenetic origin of Archean organic materials. On one hand, the occurrence of mass-independent fractionation of sulphur isotopes (MIF-S) provides a tool to test the Archean origin of ancient sedimentary rocks. Determining the isotope composition of sulphur within kerogens whilst limiting the contribution from associated minerals (e.g., nano-pyrites) is however challenging. On the other end, the Xe isotope composition of the Archean atmosphere has been shown to present enrichments in the light isotopes relative to its modern composition, together with a mono-isotopic deficit in ¹²⁹Xe. Given that the isotopic composition of atmospheric Xe evolved through time by mass dependent fractionation (MDF) until ∼2.5-2.0 Ga, the degree of MDF of Xe isotopes trapped in kerogens could provide a time stamp for the last chemical equilibration between organic matter and the atmosphere. However, the extent to which geological processes could affect the signature of Xe trapped in ancient kerogen remains unclear. In this contribution, we present new Ar, Kr and Xe isotopic data for four kerogens isolated from 3.4 to 1.8 Gy-old cherts and confirm that Xe isotopes from the Archean atmosphere can be retained within kerogens. However, new Xe-derived model ages are lower than expected from the ages of host rocks, indicating that initially trapped Xe components were at least partially lost and/or mixed together with some Xe carried out by younger generations of organic materials, therefore complicating the Xe-based dating method. Whilst non-null Δ³³S values and ¹²⁹Xe deficits relative to modern atmosphere constitute reliable imprints from the Archean atmosphere, using Xe isotopes to provide information on the syngenetic origin of ancient organic matter appears to be a promising - but not unequivocal - tool that calls for further analytical development

Soybean Seed Protein, Oil, and Fatty Acids are Altered by S and S + N Fertilizers Under Irrigated or Non-irrigated Environments

Information on the effect of sulfur (S) or sulfur+nitrogen (S + N) on soybean seed composition is scarce. Thus, the objective of this study was to investigate the effects of S, and S + N fertilizers on soybean [(Glycine max (L.) Merr.)] seed composition in the Early Soybean Production System (ESPS) under irrigated (I) and nonirrigated (NI) environments. Two separate field experiments were conducted from 2005 to 2007. One experiment was irrigated, and the second experiment was nonirrigated. Under I condition, S at a rate of 44.8 kg/ha alone or with N at 112 kg/ha resulted in a consistent increase in seed protein and oleic acid concentrations, and a decrease in oil and linolenic acid concentrations compared with the control (C). For example, in 2006 and compared with the C, application of S + N increased the percentage up to 11.4% and 48.5% for protein and oleic acid, respectively. However, oil concentration decreased by 3%. Protein and oleic acid increase were accompanied by a higher percentage of leaf and seed N and S. Under NI conditions, seed protein and oleic acid concentrations were significantly higher in C than in any S or S + N treatments, but the oil and linolenic acid concentrations were significantly lower. The results indicate that specific rate of S alone or S + N combined can alter seed composition under irrigated or nonirrigated conditions. This knowledge may help plant breeders to develop and release cultivars to suit specific target locations to grow new value-added soybeans or select for specific seed composition traits under specific environmental stress factors such as drought

A Scaling Theory of Bifurcations in the Symmetric Weak-Noise Escape Problem

We consider the overdamped limit of two-dimensional double well systems perturbed by weak noise. In the weak noise limit the most probable fluctuational path leading from either point attractor to the separatrix (the most probable escape path, or MPEP) must terminate on the saddle between the two wells. However, as the parameters of a symmetric double well system are varied, a unique MPEP may bifurcate into two equally likely MPEP's. At the bifurcation point in parameter space, the activation kinetics of the system become non-Arrhenius. In this paper we quantify the non-Arrhenius behavior of a system at the bifurcation point, by using the Maslov-WKB method to construct an approximation to the quasistationary probability distribution of the system that is valid in a boundary layer near the separatrix. The approximation is a formal asymptotic solution of the Smoluchowski equation. Our analysis relies on the development of a new scaling theory, which yields `critical exponents' describing weak-noise behavior near the saddle, at the bifurcation point.Comment: LaTeX, 60 pages, 24 Postscript figures. Uses epsf macros to include the figures. A file in `uufiles' format containing the figures is separately available at ftp://platinum.math.arizona.edu/pub/papers-rsm/paperF/figures.uu and a Postscript version of the whole paper (figures included) is available at ftp://platinum.math.arizona.edu/pub/papers-rsm/paperF/paperF.p

Luteolin Decreases EGFR-Mediated Cell Proliferation and Induces Apoptosis in Glioblastoma Cell Lines.

Glioblastomas are a subtype of gliomas, which are the most aggressive and deadly form of brain tumours. The epidermal growth factor receptor (EGFR) is over-expressed and amplified in glioblastomas. Luteolin is a common bioflavonoid found in a variety of fruits and vegetables. The aim of the present study was to explore the molecular and biological effects of luteolin on EGF-induced cell proliferation and the potential of luteolin to induce apoptosis in glioblastoma cells. In vitro cell viability assays demonstrated that luteolin decreased cell proliferation in the presence or absence of EGF. Immunoblots revealed that luteolin decreased the protein expression levels of phosphorylated Akt, mTOR, p70S6K, and MAPK in the presence of EGF. Furthermore, our results revealed the ability of luteolin to induce caspase and PARP cleavages in glioblastoma cells in addition to promoting cell cycle arrest. Our results demonstrated that luteolin has an inhibitory effect on downstream signalling molecules activated by EGFR, particularly the Akt and MAPK signalling pathways, and provided a rationale for further clinical investigation into the use of luteolin as a therapeutic molecule in the management of glioblastoma. This article is protected by copyright. All rights reserved