142 research outputs found
Growth arrest-specific gene 6 expression in human breast cancer
Growth arrest-specific gene 6 (Gas6), identified in 1995, acts as the ligand to the Axl/Tyro3 family of tyrosine kinase receptors and exerts mitogenic activity when bound to these receptors. Overexpression of the Axl/Tyro3 receptor family has been found in breast, ovarian and lung tumours. Gas6 is upregulated 23-fold by progesterone acting through the progesterone receptor B (PRB). Recently, Gas6 has been shown to be a target for overexpression and amplification in breast cancer. Quantitative real-time PCR analysis was used to determine the levels of Gas6 mRNA expression in 49 primary breast carcinomas. Expression of PRB protein was evaluated immunohistochemically with a commercially available PRB antibody. The results showed a positive association between PRB protein and Gas6 mRNA levels (P=0.04). Gas6 correlated positively with a number of favourable prognostic variables including lymph node negativity (P=0.0002), younger age at diagnosis (P=0.04), smaller size of tumours (P=0.02), low Nottingham prognostic index scores (P=0.03) and low nuclear morphology (P=0.03). This study verifies for the first time the association between PRB and Gas6 in breast cancer tissue
Pentanol isomer synthesis in engineered microorganisms
Pentanol isomers such as 2-methyl-1-butanol and 3-methyl-1-butanol are a useful class of chemicals with a potential application as biofuels. They are found as natural by-products of microbial fermentations from amino acid substrates. However, the production titer and yield of the natural processes are too low to be considered for practical applications. Through metabolic engineering, microbial strains for the production of these isomers have been developed, as well as that for 1-pentanol and pentenol. Although the current production levels are still too low for immediate industrial applications, the approach holds significant promise for major breakthroughs in production efficiency
Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses
The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined
A dearth of small particles in the transiting material around the white dwarfWD 1145+017
White dwarf WD 1145+017 is orbited by several clouds of dust, possibly
emanating from actively disintegrating bodies. These dust clouds reveal
themselves through deep, broad, and evolving transits in the star's light
curve. Here, we report two epochs of multi-wavelength photometric observations
of WD 1145+017, including several filters in the optical, K and
4.5 m bands in 2016 and 2017. The observed transit depths are different at
these wavelengths. However, after correcting for excess dust emission at
K and 4.5 m, we find the transit depths for the white dwarf
itself are the same at all wavelengths, at least to within the observational
uncertainties of 5%-10%. From this surprising result, and under the
assumption of low optical depth dust clouds, we conclude that there is a
deficit of small particles (with radii 1.5 m) in the
transiting material. We propose a model wherein only large particles can
survive the high equilibrium temperature environment corresponding to 4.5 hr
orbital periods around WD 1145+017, while small particles sublimate rapidly. In
addition, we evaluate dust models that are permitted by our measurements of
infrared emission
Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project
<p>Abstract</p> <p>Background</p> <p>There is a lack of knowledge regarding the frequency of disease associated polymorphisms in populations and population attributable risk for many populations remains unknown. Factors that could affect the association of the allele with disease, either positively or negatively, such as race, ethnicity, and gender, may not be possible to determine without population based allele frequencies.</p> <p>Here we used a panel of 51 polymorphisms previously associated with at least one disease and determined the allele frequencies within the entire Personalized Medicine Research Project population based cohort. We compared these allele frequencies to those in dbSNP and other data sources stratified by race. Differences in allele frequencies between self reported race, region of origin, and sex were determined.</p> <p>Results</p> <p>There were 19544 individuals who self reported a single racial category, 19027 or (97.4%) self reported white Caucasian, and 11205 (57.3%) individuals were female. Of the 11,208 (57%) individuals with an identifiable region of origin 8337 or (74.4%) were German.</p> <p>41 polymorphisms were significantly different between self reported race at the 0.05 level. Stratification of our Caucasian population by self reported region of origin revealed 19 polymorphisms that were significantly different (p = 0.05) between individuals of different origins. Further stratification of the population by gender revealed few significant differences in allele frequencies between the genders.</p> <p>Conclusions</p> <p>This represents one of the largest population based allele frequency studies to date. Stratification by self reported race and region of origin revealed wide differences in allele frequencies not only by race but also by region of origin within a single racial group. We report allele frequencies for our Asian/Hmong and American Indian populations; these two minority groups are not typically selected for population allele frequency detection. Population wide allele frequencies are important for the design and implementation of studies and for determining the relevance of a disease associated polymorphism for a given population.</p
IL1B-CGTC haplotype is associated with colorectal cancer in admixed individuals with increased African ancestry
Single-nucleotide polymorphisms (SNPs) in cytokine genes can affect gene expression and thereby modulate inflammation and carcinogenesis. However, the data on the association between SNPs in the interleukin 1 beta gene (IL1B) and colorectal cancer (CRC) are conflicting. We found an association between a 4-SNP haplotype block of the IL1B (-3737C/-1464G/-511T/-31C) and CRC risk, and this association was exclusively observed in individuals with a higher proportion of African ancestry, such as individuals from the Coastal Colombian region (odds ratio, OR 2.06; 95% CI 1.31β3.25; pβ<β0.01). Moreover, a significant interaction between this CRC risk haplotype and local African ancestry dosage was identified in locus 2q14 (pβ=β0.03). We conclude that Colombian individuals with high African ancestry proportions at locus 2q14 harbour more IL1B-CGTC copies and are consequently at an increased risk of CRC. This haplotype has been previously found to increase the IL1B promoter activity and is the most frequent haplotype in African Americans. Despite of limitations in the number of samples and the lack of functional analysis to examine the effect of these haplotypes on CRC cell lines, our results suggest that inflammation and ethnicity play a major role in the modulation of CRC risk
The Founderβs Lecture 2009: advances in imaging of osteoporosis and osteoarthritis
The objective of this review article is to provide an update on new developments in imaging of osteoporosis and osteoarthritis over the past three decades. A literature review is presented that summarizes the highlights in the development of bone mineral density measurements, bone structure imaging, and vertebral fracture assessment in osteoporosis as well as MR-based semiquantitative assessment of osteoarthritis and quantitative cartilage matrix imaging. This review focuses on techniques that have impacted patient management and therapeutic decision making or that potentially will affect patient care in the near future. Results of pertinent studies are presented and used for illustration. In summary, novel developments have significantly impacted imaging of osteoporosis and osteoarthritis over the past three decades
Sex-Specific Genetic Structure and Social Organization in Central Asia: Insights from a Multi-Locus Study
In the last two decades, mitochondrial DNA (mtDNA) and the non-recombining portion of the Y chromosome (NRY) have been extensively used in order to measure the maternally and paternally inherited genetic structure of human populations, and to infer sex-specific demography and history. Most studies converge towards the notion that among populations, women are genetically less structured than men. This has been mainly explained by a higher migration rate of women, due to patrilocality, a tendency for men to stay in their birthplace while women move to their husband's house. Yet, since population differentiation depends upon the product of the effective number of individuals within each deme and the migration rate among demes, differences in male and female effective numbers and sex-biased dispersal have confounding effects on the comparison of genetic structure as measured by uniparentally inherited markers. In this study, we develop a new multi-locus approach to analyze jointly autosomal and X-linked markers in order to aid the understanding of sex-specific contributions to population differentiation. We show that in patrilineal herder groups of Central Asia, in contrast to bilineal agriculturalists, the effective number of women is higher than that of men. We interpret this result, which could not be obtained by the analysis of mtDNA and NRY alone, as the consequence of the social organization of patrilineal populations, in which genetically related men (but not women) tend to cluster together. This study suggests that differences in sex-specific migration rates may not be the only cause of contrasting male and female differentiation in humans, and that differences in effective numbers do matter
Combined low initial DNA damage and high radiation-induced apoptosis confers clinical resistance to long-term toxicity in breast cancer patients treated with high-dose radiotherapy
Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND. Either higher levels of initial DNA damage or lower levels of radiation-induced apoptosis in peripheral blood lymphocytes have been associated to increased risk for develop late radiation-induced toxicity. It has been recently published that these two predictive tests are inversely related. The aim of the present study was to investigate the combined role of both tests in relation to clinical radiation-induced toxicity in a set of breast cancer patients treated with high dose hyperfractionated radical radiotherapy. METHODS. Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma treated with high-dose hyperfractioned radical radiotherapy. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity scoring schema. The mean follow-up of survivors (n = 13) was 197.23 months. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radiation-induced apoptosis (RIA) at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide.
RESULTS. Mean DSB/Gy/DNA unit obtained was 1.70 Β± 0.83 (range 0.63-4.08; median, 1.46). Radiation-induced apoptosis increased with radiation dose (median 12.36, 17.79 and 24.83 for 1, 2, and 8 Gy respectively). We observed that those "expected resistant patients" (DSB values lower than 1.78 DSB/Gy per 200 Mbp and RIA values over 9.58, 14.40 or 24.83 for 1, 2 and 8 Gy respectively) were at low risk of suffer severe subcutaneous late toxicity (HR 0.223, 95%CI 0.073-0.678, P = 0.008; HR 0.206, 95%CI 0.063-0.677, P = 0.009; HR 0.239, 95%CI 0.062-0.929, P = 0.039, for RIA at 1, 2 and 8 Gy respectively) in multivariate analysis. CONCLUSIONS. A radiation-resistant profile is proposed, where those patients who presented lower levels of initial DNA damage and higher levels of radiation induced apoptosis were at low risk of suffer severe subcutaneous late toxicity after clinical treatment at high radiation doses in our series. However, due to the small sample size, other prospective studies with higher number of patients are needed to validate these results.This work was subsidized by a grant from the Ministerio de EducaciΓ³n y Ciencia (CICYT: SAF 2004-00889) and FundaciΓ³n del Instituto Canario de InvestigaciΓ³n del CΓ‘ncer (FICIC).Yes2011-0
The Fecal Viral Flora of Wild Rodents
The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat) collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in mammals
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