3,010 research outputs found

    Barium Promotes Anchorage-Independent Growth and Invasion of Human HaCaT Keratinocytes via Activation of c-SRC Kinase

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    Explosive increases in skin cancers have been reported in more than 36 million patients with arsenicosis caused by drinking arsenic-polluted well water. This study and previous studies showed high levels of barium as well as arsenic in the well water. However, there have been no reports showing a correlation between barium and cancer. In this study, we examined whether barium (BaCl2) may independently have cancer-related effects on human precancerous keratinocytes (HaCaT). Barium (5–50 ”M) biologically promoted anchorage-independent growth and invasion of HaCaT cells in vitro. Barium (5 ”M) biochemically enhanced activities of c-SRC, FAK, ERK and MT1-MMP molecules, which regulate anchorage-independent growth and/or invasion. A SRC kinase specific inhibitor, protein phosphatase 2 (PP2), blocked barium-mediated promotion of anchorage-independent growth and invasion with decreased c-SRC kinase activity. Barium (2.5–5 ”M) also promoted anchorage-independent growth and invasion of fibroblasts (NIH3T3) and immortalized nontumorigenic melanocytes (melan-a), but not transformed cutaneous squamous cell carcinoma (HSC5 and A431) and malignant melanoma (Mel-ret) cells, with activation of c-SRC kinase. Taken together, our biological and biochemical findings newly suggest that the levels of barium shown in drinking well water independently has the cancer-promoting effects on precancerous keratinocytes, fibroblast and melanocytes in vitro

    Minimum-Uncertainty Angular Wave Packets and Quantized Mean Values

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    Uncertainty relations between a bounded coordinate operator and a conjugate momentum operator frequently appear in quantum mechanics. We prove that physically reasonable minimum-uncertainty solutions to such relations have quantized expectation values of the conjugate momentum. This implies, for example, that the mean angular momentum is quantized for any minimum-uncertainty state obtained from any uncertainty relation involving the angular-momentum operator and a conjugate coordinate. Experiments specifically seeking to create minimum-uncertainty states localized in angular coordinates therefore must produce packets with integer angular momentum.Comment: accepted for publication in Physical Review

    Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

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    To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

    On absolute continuity of the spectrum of a periodic magnetic Schr\"odinger operator

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    We consider the Schr\"odinger operator in Rn{\mathbb R}^n, n≄3n\geq 3, with the electric potential VV and the magnetic potential AA being periodic functions (with a common period lattice) and prove absolute continuity of the spectrum of the operator in question under some conditions which, in particular, are satisfied if V∈Llocn/2(Rn)V\in L^{n/2}_{{\mathrm {loc}}}({\mathbb R}^n) and A∈Hlocq(Rn;Rn)A\in H^q_{{\mathrm {loc}}}({\mathbb R}^n;{\mathbb R}^n), q>(n−1)/2q>(n-1)/2.Comment: 25 page

    Bisphenol A exposure in Mexico City and risk of prematurity: a pilot nested case control study

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    Abstract Background Presence of Bisphenol A (BPA) has been documented worldwide in a variety of human biological samples. There is growing evidence that low level BPA exposure may impact placental tissue development and thyroid function in humans. The aim of this present pilot study was to determine urinary concentrations of BPA during the last trimester of pregnancy among a small subset of women in Mexico City, Mexico and relate these concentrations to risk of delivering prematurely. Methods A nested case-control subset of 60 participants in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) study in Mexico City, Mexico were selected based on delivering less than or equal to 37 weeks of gestation and greater than 37 weeks of gestation. Third trimester archived spot urine samples were analyzed by online solid phase extraction coupled with high performance liquid chromatography isotope dilution tandem mass spectrometry. Results BPA was detected in 80.0% (N = 48) of the urine samples; total concentrations ranged from < 0.4 μg/L to 6.7 μg/L; uncorrected geometric mean was 1.52 μg/L. The adjusted odds ratio of delivering less than or equal to 37 weeks in relation to specific gravity adjusted third trimester BPA concentration was 1.91 (95%CI 0.93, 3.91, p-value = 0.08). When cases were further restricted to births occurring prior to the 37th week (n = 12), the odds ratio for specific-gravity adjusted BPA was larger and statistically significant (p < 0.05). Conclusions This is the first study to document measurable levels of BPA in the urine of a population of Mexican women. This study also provides preliminary evidence, based on a single spot urine sample collected during the third trimester, that pregnant women who delivered less than or equal to 37 weeks of gestation and prematurely (< 37 weeks) had higher urinary concentrations of BPA compared to women delivering after 37 weeks.http://deepblue.lib.umich.edu/bitstream/2027.42/78251/1/1476-069X-9-62.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78251/2/1476-069X-9-62.pdfPeer Reviewe

    Environmental differences between sites control the diet and nutrition of the carnivorous plant Drosera rotundifolia

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    Background and aims: Carnivorous plants are sensitive to small changes in resource availability, but few previous studies have examined how differences in nutrient and prey availability affect investment in and the benefit of carnivory. We studied the impact of site-level differences in resource availability on ecophysiological traits of carnivory for Drosera rotundifolia L. Methods: We measured prey availability, investment in carnivory (leaf stickiness), prey capture and diet of plants growing in two bogs with differences in N deposition and plant available N: Cors Fochno (0.62 g m−2 yr.−1, 353 ÎŒg l−1), Whixall Moss (1.37 g m−2 yr.−1, 1505 ÎŒg l−1). The total N amount per plant and the contributions of prey/root N to the plants’ N budget were calculated using a single isotope natural abundance method. Results: Plants at Whixall Moss invested less in carnivory, were less likely to capture prey, and were less reliant on prey-derived N (25.5% compared with 49.4%). Actual prey capture did not differ between sites. Diet composition differed – Cors Fochno plants captured 62% greater proportions of Diptera. Conclusions: Our results show site-level differences in plant diet and nutrition consistent with differences in resource availability. Similarity in actual prey capture may be explained by differences in leaf stickiness and prey abundance

    RNA secondary structure prediction from multi-aligned sequences

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    It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

    Molecular Epidemiology of HIV-Associated Tuberculosis in Dar es Salaam, Tanzania: Strain Predominance, Clustering, and Polyclonal Disease.

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    Molecular typing of Mycobacterium tuberculosis can be used to elucidate the epidemiology of tuberculosis, including the rates of clustering, the frequency of polyclonal disease, and the distribution of genotypic families. We performed IS6110 typing and spoligotyping on M. tuberculosis strains isolated from HIV-infected subjects at baseline or during follow-up in the DarDar Trial in Tanzania and on selected community isolates. Clustering occurred in 203 (74%) of 275 subjects: 124 (80%) of 155 HIV-infected subjects with baseline isolates, 56 (69%) of 81 HIV-infected subjects with endpoint isolates, and 23 (59%) of 39 community controls. Overall, 113 (41%) subjects had an isolate representing the East Indian "GD" family. The rate of clustering was similar among vaccine and placebo recipients and among subjects with or without cellular immune responses to mycobacterial antigens. Polyclonal disease was detected in 6 (43%) of 14 patients with multiple specimens typed. Most cases of HIV-associated tuberculosis among subjects from this study in Dar es Salaam resulted from recently acquired infection. Polyclonal infection was detected and isolates representing the East Indian GD strain family were the most common
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