Nucleolar organization, ribosomal DNA array stability, and acrocentric chromosome integrity are linked to telomere function.

The short arms of the ten acrocentric human chromosomes share several repetitive DNAs, including ribosomal RNA genes (rDNA). The rDNA arrays correspond to nucleolar organizing regions that coalesce each cell cycle to form the nucleolus. Telomere disruption by expressing a mutant version of telomere binding protein TRF2 (dnTRF2) causes non-random acrocentric fusions, as well as large-scale nucleolar defects. The mechanisms responsible for acrocentric chromosome sensitivity to dysfunctional telomeres are unclear. In this study, we show that TRF2 normally associates with the nucleolus and rDNA. However, when telomeres are crippled by dnTRF2 or RNAi knockdown of TRF2, gross nucleolar and chromosomal changes occur. We used the controllable dnTRF2 system to precisely dissect the timing and progression of nucleolar and chromosomal instability induced by telomere dysfunction, demonstrating that nucleolar changes precede the DNA damage and morphological changes that occur at acrocentric short arms. The rDNA repeat arrays on the short arms decondense, and are coated by RNA polymerase I transcription binding factor UBF, physically linking acrocentrics to one another as they become fusogenic. These results highlight the importance of telomere function in nucleolar stability and structural integrity of acrocentric chromosomes, particularly the rDNA arrays. Telomeric stress is widely accepted to cause DNA damage at chromosome ends, but our findings suggest that it also disrupts chromosome structure beyond the telomere region, specifically within the rDNA arrays located on acrocentric chromosomes. These results have relevance for Robertsonian translocation formation in humans and mechanisms by which acrocentric-acrocentric fusions are promoted by DNA damage and repair

On the choice of ensemble mean for estimating the forced signal in the presence of internal variability

This is the final version of the article. Available from American Meteorological Society via the DOI in this record.In this paper we examine various options for the calculation of the forced signal in climate model simulations, and the impact these choices have on the estimates of internal variability. We find that an ensemble mean of runs from a single climate model [a single model ensemble mean (SMEM)] provides a good estimate of the true forced signal even for models with very few ensemble members. In cases where only a single member is available for a given model, however, the SMEM from other models is in general out-performed by the scaled ensemble mean from all available climate model simulations [the multimodel ensemble mean (MMEM)]. The scaled MMEM may therefore be used as an estimate of the forced signal for observations. The MMEM method, however, leads to increasing errors further into the future, as the different rates of warming in the models causes their trajectories to diverge. We therefore apply the SMEM method to those models with a sufficient number of ensemble members to estimate the change in the amplitude of internal variability under a future forcing scenario. In line with previous results, we find that on average the surface air temperature variability decreases at higher latitudes, particularly over the ocean along the sea ice margins, while variability in precipitation increases on average, particularly at high latitudes. Variability in sea level pressure decreases on average in the Southern Hemisphere, while in the Northern Hemisphere there are regional differences.This work was supported by the Australian Research Council (ARC) through grants to L. M. F. (DE170100367) and to M. H. E. through the ARC Centre of Excellence in Climate System Science (CE110001028). J. B. K. is supported by the Natural Environment Research Council (Grant NE/N005783/1). B. A. S. was supported by the U.S. National Science Foundation (EAR-1447048)

Comparative Antioxidant, Antiproliferative and Apoptotic Effects of Ilex laurina and Ilex paraguariensis on Colon Cancer Cells

Purpose: To determine and compare the antioxidant, antiproliferative and apoptotic effects of leaf infusions of Ilex laurina and Ilex paraguariensis in colon cancer cells.Methods: Antioxidant activity was determined by ORAC (Oxygen Radical Absorbance Capacity) and FRAP (Ferric Reducing Antioxidant Power). Cytotoxic and antiproliferative effects were analyzed using MTT ((3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) and sulfhorodamine-B respectively. Cell death and apoptosis of human colon adenocarcinoma cells SW480 and their metastatic-derived SW620 cells, were analyzed by flow cytometry using propidium iodide and Annexin-V.Results: Although their flavonoid levels were similar, I. laurina infusion contained 2.2 and 4.4 times higher amounts of total phenolic and caffeoyl derivatives, respectively, than I. paraguariensis. FRAP and ORAC values for I. laurina infusion were 1.6 and 2.0 more active than I. paraguariensis. Both plant infusions inhibited viability and cell growth of SW480 and SW620 cells. These results may be associated to cell cycle-arrest and apoptosis because of the comparable increase of hypodiploid and annexin-V positive colon cancer cells.Conclusion: These data highlight the antioxidant and promising anticancer activities of I. laurina and Ilex paraguariensis.Keywords: Ilex laurina, Ilex paraguariensis, Antioxidant, Antiproliferative, Apoptosis, Colon cance

Norovirus Infection and Disease in an Ecuadorian Birth Cohort: Association of Certain Norovirus Genotypes With Host FUT2 Secretor Status.

BACKGROUND: Although norovirus is the most common cause of gastroenteritis, there are few data on the community incidence of infection/disease or the patterns of acquired immunity or innate resistance to norovirus. METHODS: We followed a community-based birth cohort of 194 children in Ecuador with the aim to estimate (1) the incidence of norovirus gastroenteritis from birth to age 3 years, (2) the protective effect of norovirus infection against subsequent infection/disease, and (3) the association of infection and disease with FUT2 secretor status. RESULTS: Over the 3-year period, we detected a mean of 2.26 diarrheal episodes per child (range, 0-12 episodes). Norovirus was detected in 260 samples (18%) but was not found more frequently in diarrheal samples (79 of 438 [18%]), compared with diarrhea-free samples (181 of 1016 [18%]; P = .919). A total of 66% of children had at least 1 norovirus infection during the first 3 years of life, and 40% of children had 2 infections. Previous norovirus infections were not associated with the risk of subsequent infection. All genogroup II, genotype 4 (GII.4) infections were among secretor-positive children (P < .001), but higher rates of non-GII.4 infections were found in secretor-negative children (relative risk, 0.56; P = .029). CONCLUSIONS: GII.4 infections were uniquely detected in secretor-positive children, while non-GII.4 infections were more often found in secretor-negative children

A study of arsenic speciation in soil, irrigation water and plant tissue: A case study of the broad bean plant, Vicia faba.

Samples of soil, the broad bean plant, Vicia faba and irrigation water were collected from the same agricultural site in Dokan, in the Kurdistan region of Iraq. Total arsenic and arsenic speciation were determined in all materials by ICP-MS and HPLC-ICP-MS, respectively. Available arsenic (11%) was also determined within the soil, together with Cd, Cr, Cu, Ni, Zn, Fe and Mn. The concentrations of total arsenic were: soil (5.32μgg(-1)), irrigation water (1.06μgL(-1)), roots (2.065μgg(-1)) and bean (0.133μgg(-1)). Stems, leaves and pods were also measured. Inorganic As(V) dominated soil (90%) and root (78%) samples. However, organo-arsenic (MMA, 48% and DMA, 19%) was the more dominant species in the edible bean. The study provides an insight into the uptake, preferred disposal route, speciation changes and loss mechanism involved for arsenic with this food source

Dynamics of localization in a waveguide

This is a review of the dynamics of wave propagation through a disordered N-mode waveguide in the localized regime. The basic quantities considered are the Wigner-Smith and single-mode delay times, plus the time-dependent power spectrum of a reflected pulse. The long-time dynamics is dominated by resonant transmission over length scales much larger than the localization length. The corresponding distribution of the Wigner-Smith delay times is the Laguerre ensemble of random-matrix theory. In the power spectrum the resonances show up as a 1/t^2 tail after N^2 scattering times. In the distribution of single-mode delay times the resonances introduce a dynamic coherent backscattering effect, that provides a way to distinguish localization from absorption.Comment: 18 pages including 8 figures; minor correction

Heavy Quarkonium in a weakly-coupled quark-gluon plasma below the melting temperature

We calculate the heavy quarkonium energy levels and decay widths in a quark-gluon plasma, whose temperature T and screening mass m_D satisfy the hierarchy m alpha_s >> T >> m alpha_s^2 >> m_D (m being the heavy-quark mass), at order m alpha_s^5. We first sequentially integrate out the scales m, m alpha_s and T, and, next, we carry out the calculations in the resulting effective theory using techniques of integration by regions. A collinear region is identified, which contributes at this order. We also discuss the implications of our results concerning heavy quarkonium suppression in heavy ion collisions.Comment: 25 pages, 2 figure

Fluorescence Resonance Energy Transfer (FRET) as a method to calculate the dimerization strength of basic Helix-Loop-Helix (bHLH) proteins

Post-translational modifications such as phosphorylation play a vital role in the regulation of protein function. In our study of the basic Helix-loop-Helix (bHLH) transcription factor HAND1, we show that HAND1 is phosphorylated during the trophoblast giant cell differentiation on residues residing in Helix I of the bHLH domain. Our hypothesis is that these modifications result in changes in HAND1 dimerization affinities with other bHLH factors. To test this idea, we employed FRET to measure the protein-protein interactions of HAND1 and HAND1 point mutants in HEK293 cells using YFP and CFP fusion proteins and laser scanning confocal microscopy