The effects of 5-fluorouracil and doxorubicin on expression of human immunodeficiency virus type 1 long terminal repeat

Previous work by many groups has documented induction of the HIV-LTR following exposure of cells to ultraviolet light and other DNA damaging agents. Our experiments set out to determine the relative activation or repression of the HIV-LTR in response to two classes of chemotherapeutic agents: Doxorubicin is a DNA-damage inducing agent, and 5-fluorouracil has an antimetabolic mode of action. Using HeLa cells stably transfected with a construct in which HIV-LTR drives expression of the chloramphenicol acetyl transferase reporter gene, we demonstrated an up to 10-fold induction following doxorubicin treatment in 24 h post-treatment. This induction was repressed by treatment with salicylic acid, suggesting a role for prostaglandin/cyclo-oxygenase pathways and/or NFKB in the inductive response. Induction by 5-fluorouracil, in contrast, was more modest (two-fold at most) though it was consistently elevated over controls

Dietary elimination of children with food protein induced gastrointestinal allergy – micronutrient adequacy with and without a hypoallergenic formula?

Background: The cornerstone for management of Food protein-induced gastrointestinal allergy (FPGIA) is dietary exclusion; however the micronutrient intake of this population has been poorly studied. We set out to determine the dietary intake of children on an elimination diet for this food allergy and hypothesised that the type of elimination diet and the presence of a hypoallergenic formula (HF) significantly impacts on micronutrient intake. Method: A prospective observational study was conducted on children diagnosed with FPIGA on an exclusion diet who completed a 3 day semi-quantitative food diary 4 weeks after commencing the diet. Nutritional intake where HF was used was compared to those without HF, with or without a vitamin and mineral supplement (VMS). Results: One-hundred-and-five food diaries were included in the data analysis: 70 boys (66.7%) with median age of 21.8 months [IQR: 10 - 67.7]. Fifty-three children (50.5%) consumed a HF and the volume of consumption was correlated to micronutrient intake. Significantly (p <0.05) more children reached their micronutrient requirements if a HF was consumed. In those without a HF, some continued not to achieve requirements in particular for vitamin D and zinc, in spite of VMS. Conclusion: This study points towards the important micronutrient contribution of a HF in children with FPIGA. Children, who are not on a HF and without a VMS, are at increased risk of low intakes in particular vitamin D and zinc. Further studies need to be performed, to assess whether dietary intake translates into actual biological deficiencies

Severe thrombocytosis and anemia associated with celiac disease in a young female patient: a case report

<p>Abstract</p> <p>Introduction</p> <p>Platelet counts exceeding 1.000 × 10³/μl are usually considered secondary to another cause, particularly to chronic myeloproliferative disease (CMPD). Reactive thrombocytosis due to iron deficiency rarely exceeds platelet counts of 700 × 10³/μl.</p> <p>Case presentation</p> <p>Here we report the case of a young woman presenting with clinical signs of severe anemia. Laboratory findings confirmed an iron-deficiency anemia associated with severe thrombocytosis of 1703 × 10³/μl. Macroscopic gastrointestinal and genitourinary tract bleeding was excluded. The excessive elevation of platelets, slightly elevated lactate dehydrogenase and slightly elevated leukocytes along with the absence of other inflammation parameters raised the suspicion of an underlying hematological disease. However, bone marrow evaluation could not prove the suspected diagnosis of a CMPD, especially essential thrombocythemia (ET). In the further clinical course the platelet count returned to normal after raising the hemoglobin to a level close to normal range with erythrocyte transfusion, and normalization of serum iron and decline of erythropoietin. Finally, following small bowel biopsy, despite the absence of typical clinical signs, celiac disease was diagnosed. After discharge from hospital the patient was commenced on a gluten-free diet and her hemoglobin almost completely normalized in the further follow-up period.</p> <p>Conclusion</p> <p>This case illustrates the rare constellation of an extreme thrombocytosis most likely secondary to iron deficiency due to celiac disease. This represents, to the best of the authors' knowledge, the highest reported platelet count coincident with iron deficiency. A potential mechanism for the association of iron-deficiency anemia and thrombocytosis is discussed. Even in the presence of 'atypically' high platelets one should consider the possibility of reactive thrombocytosis. Extreme thrombocytosis could emerge in the case of iron deficiency secondary to celiac disease.</p

Integrated Genetic and Epigenetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus

Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D), focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip) and absolute methylation values were estimated using a Bayesian algorithm (BATMAN). Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p = 9.40×10−4, permutation p = 1.0×10−3). Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p = 1.13×10−7). Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM), encapsulates a Highly Conserved Non-Coding Element (HCNE) that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA) SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases

Can You Hear us Now? Voices from the Margin: Using Indigenous Methodologies in Geographic Research

Indigenous methodologies are an alternative way of thinking about research processes. Although these methodologies vary according to the ways in which different Indigenous communities express their own unique knowledge systems, they do have common traits. This article argues that research on Indigenous issues should be carried out in a manner which is respectful and ethically sound from an Indigenous perspective. This naturally challenges Western research paradigms, yet it also affords opportunities to contribute to the body of knowledge about Indigenous peoples. It is further argued that providing a mechanism for Indigenous peoples to participate in and direct these research agendas ensures that their communal needs are met, and that geographers then learn how to build ethical research relationships with them. Indigenous methodologies do not privilege Indigenous researchers because of their Indigeneity, since there are many ‘insider’ views, and these are thus suitable for both Indigenous and non-Indigenous researchers. However, there is a difference between research done within an Indigenous context using Western methodologies and research done using Indig- enous methodologies which integrates Indigenous voices. This paper will discuss those differences while presenting a historical context of research on Indigenous peoples, providing further insights into what Indigenous methodologies entail, and proposing ways in which the academy can create space for this discourse

Teaching the Academic Word List in Foreign Language Speaking Classes

WOS: 00043485270039

Internet Daters’ Body Type Preferences: Race–Ethnic and Gender Differences

Employing a United States sample of 5,810 Yahoo heterosexual internet dating profiles, this study finds race–ethnicity and gender influence body type preferences for dates, with men and whites significantly more likely than women and non-whites to have such preferences. White males are more likely than non-white men to prefer to date thin and toned women, while African-American and Latino men are significantly more likely than white men to prefer female dates with thick or large bodies. Compatible with previous research showing non-whites have greater body satisfaction and are less influenced by mainstream media than whites, our findings suggest Latinos and African Americans negotiate dominant white idealizations of thin female bodies with their own cultures’ greater acceptance of larger body types

Source Evaluation and Trace Metal Contamination in Benthic Sediments from Equatorial Ecosystems Using Multivariate Statistical Techniques

race metals (Cd, Cr, Cu, Ni and Pb) concentrations in benthic sediments were analyzed through multi-step fractionation scheme to assess the levels and sources of contamination in estuarine, riverine and freshwater ecosystems in Niger Delta (Nigeria). The degree of contamination was assessed using the individual contamination factors (ICF) and global contamination factor (GCF). Multivariate statistical approaches including principal component analysis (PCA), cluster analysis and correlation test were employed to evaluate the interrelationships and associated sources of contamination. The spatial distribution of metal concentrations followed the pattern Pb>Cu>Cr>Cd>Ni. Ecological risk index by ICF showed significant potential mobility and bioavailability for Cu, Cu and Ni. The ICF contamination trend in the benthic sediments at all studied sites was Cu>Cr>Ni>Cd>Pb. The principal component and agglomerative clustering analyses indicate that trace metals contamination in the ecosystems was influenced by multiple pollution sources

Multimode Pulsations of the λ Bootis Star 29 Cygni: The 1995 and 1996 Multisite Campaigns

In this paper we present the results of multisite photometric and spectroscopic campaigns, carried out during the years 1995 and 1996, to study the pulsations of a typical λ Bootis star, 29 Cyg. During the 1995 campaign we found well-defined multiperiodicity in 29 Cyg, which was studied in detail during a multilongitude campaign covering a 65 day time interval in 1996. The frequency analysis of the 1996 campaign's data easily revealed 11 excited low ℓ degree modes with frequencies of oscillation ranging from 20.3 to 37.4 cycles day-1 and mean photometric amplitudes ranging from 10.65 to 0.96 mmag in the V filter. After removing the well-identified frequencies, the discrete Fourier transform of the residuals showed excess power in the 20-40 cycle day-1 domain, which indicates the probable existence of unresolved rich p-mode spectra with photometric V amplitudes below 0.5 mmag. We found a regular spacing of 2.41 cycles day-1 within the modes of 29 Cyg, which was interpreted as the spacing of consecutive even and odd ℓ-values. The asteroseismic luminosity log L/L⊙ = 1.12, calculated from the frequency spacing, is in good agreement with the Hipparcos luminosity log L/L⊙ = 1.16 and with luminosities from photometric and spectroscopic calibrations. Using our multicolor photometry we tentatively identified the dominant f1 = 37.425 cycle day -1 mode as an ℓ= 2, n = 5 mode, and made radial overtone identification for all frequencies. These ranged from n = 2 to 5. Analysis of the photometric data shows the long-term (years) and probable short-term (days) variability of amplitudes for all of these modes in 29 Cyg. Using our multicolor WBVR filter photometry, we found the wavelength dependence of the pulsation amplitudes for the five highest amplitude modes. Based on the Hα line radial velocity observations of 29 Cyg, we detected multiperiodic radial velocity variations with frequencies of 38.36 and 29.99 cycles day-1 and semiamplitudes of 1.0 and 0.8 km s-1, respectively. These frequencies coincide within the errors with the photometric frequencies of the two highest amplitude modes, 37.425 and 29.775 cycles day-1. For the highest amplitude ℓ = 2, n = 5 mode (37.425 cycles day-1), the radial velocity-to-light amplitude ratio and velocity-to-light phase shift are equal to 2K(Hα)/ Δ V = 94 km mag-1 s-1 and Φf1 = φVr - φV = +0.08 ± 0.01, respectively, and are in good agreement with values for δ Scuti stars. The rich multiperiodic spectrum makes 29 Cyg a promising target for future multisite campaigns. © 2007. The American Astronomical Society. All rights reserved.M. D. E. and K. Y. W. acknowledge their work as part of the research activity of the Astrophysical Research Center for the Structure and Evolution of the Cosmos, which is supported by the Korean Science and Engineering Foundation. The participation of G. H., E. P., and W. W. was supported by the Austrian Fonds zur Förderung der wissenschaftlichen Forschung under grant S-7303. The spectroscopic observations described in this publication were made possible in part by grants R2Q000 and U1C000 from the International Science Foundation and by grant A-05-067 from the ESO C&EE programme. This work was supported in part by US Civilian and Research Development Foundation grant UP2-317.Peer reviewe