Evidence for Divisome Localization Mechanisms Independent of the Min System and SlmA in Escherichia coli

Cell division in Escherichia coli starts with assembly of FtsZ protofilaments into a ring-like structure, the Z-ring. Positioning of the Z-ring at midcell is thought to be coordinated by two regulatory systems, nucleoid occlusion and the Min system. In E. coli, nucleoid occlusion is mediated by the SlmA proteins. Here, we address the question of whether there are additional positioning systems that are capable of localizing the E. coli divisome with respect to the cell center. Using quantitative fluorescence imaging we show that slow growing cells lacking functional Min and SlmA nucleoid occlusion systems continue to divide preferentially at midcell. We find that the initial Z-ring assembly occurs over the center of the nucleoid instead of nucleoid-free regions under these conditions. We determine that Z-ring formation begins shortly after the arrival of the Ter macrodomain at the nucleoid center. Removal of either the MatP, ZapB, or ZapA proteins significantly affects the accuracy and precision of Z-ring positioning relative to the nucleoid center in these cells in accordance with the idea that these proteins link the Ter macrodomain and the Z-ring. Interestingly, even in the absence of Min, SlmA, and the putative Ter macrodomain – Z-ring link, there remains a weak midcell positioning bias for the Z-ring. Our work demonstrates that additional Z-ring localization systems are present in E. colithan are known currently. In particular, we identify that the Ter macrodomain acts as a landmark for the Z-ring in the presence of MatP, ZapB and ZapA proteins

X-Ray and UV Orbital Phase Dependence in LMC X-3

The black-hole binary LMC X-3 is known to be variable on time scales of days to years. We investigate X-ray and ultraviolet variability in the system as a function of the 1.7 day binary phase using a 6.4 day observation with the Rossi X-ray Timing Explorer (RXTE) from December 1998. An abrupt 14% flux decrease, lasting nearly an entire orbit, is followed by a return to previous flux levels. This behavior occurs twice, at nearly the same binary phase, but it is not present in consecutive orbits. When the X-ray flux is at lower intensity, a periodic amplitude modulation of 7% is evident in data folded modulo the orbital period. The higher intensity data show weaker correlation with phase. This is the first report of X-ray variability at the orbital period of LMC X-3. Archival RXTE observations of LMC X--3 during a high flux state in December 1996 show similar phase dependence. An ultraviolet light curve obtained with the High Speed Photometer aboard the Hubble Space Telescope shows orbital modulation consistent with that in the optical, caused by the ellipsoidal variation of the spatially deformed companion. The X-ray spectrum of LMC X-3 can be acceptably represented by a phenomenological disk-black-body plus a power law. Changes in the spectrum of LMC X-3 during our observations are compatible with earlier observations during which variations in the 2-10 keV flux are tracked closely by the disk geometry spectral model parameter.Comment: 11 pages, 7 figures, ApJ in pres

Breast cancer risk factors and a novel measure of volumetric breast density: cross-sectional study

We conducted a cross-sectional study nested within a prospective cohort of breast cancer risk factors and two novel measures of breast density volume among 590 women who had attended Glasgow University (1948–1968), replied to a postal questionnaire (2001) and attended breast screening in Scotland (1989–2002). Volumetric breast density was estimated using a fully automated computer programme applied to digitised film-screen mammograms, from medio-lateral oblique mammograms at the first-screening visit. This measured the proportion of the breast volume composed of dense (non-fatty) tissue (Standard Mammogram Form (SMF)%) and the absolute volume of this tissue (SMF volume, cm3). Median age at first screening was 54.1 years (range: 40.0–71.5), median SMF volume 70.25 cm3 (interquartile range: 51.0–103.0) and mean SMF% 26.3%, s.d.=8.0% (range: 12.7–58.8%). Age-adjusted logistic regression models showed a positive relationship between age at last menstrual period and SMF%, odds ratio (OR) per year later: 1.05 (95% confidence interval: 1.01–1.08, P=0.004). Number of pregnancies was inversely related to SMF volume, OR per extra pregnancy: 0.78 (0.70–0.86, P<0.001). There was a suggestion of a quadratic relationship between birthweight and SMF%, with lowest risks in women born under 2.5 and over 4 kg. Body mass index (BMI) at university (median age 19) and in 2001 (median age 62) were positively related to SMF volume, OR per extra kg m−2 1.21 (1.15–1.28) and 1.17 (1.09–1.26), respectively, and inversely related to SMF%, OR per extra kg m−2 0.83 (0.79–0.88) and 0.82 (0.76–0.88), respectively, P<0.001. Standard Mammogram Form% and absolute SMF volume are related to several, but not all, breast cancer risk factors. In particular, the positive relationship between BMI and SMF volume suggests that volume of dense breast tissue will be a useful marker in breast cancer studies

Influence of Gamma-Ray Emission on the Isotopic Composition of Clouds in the Interstellar Medium

We investigate one mechanism of the change in the isotopic composition of cosmologically distant clouds of interstellar gas whose matter was subjected only slightly to star formation processes. According to the standard cosmological model, the isotopic composition of the gas in such clouds was formed at the epoch of Big Bang nucleosynthesis and is determined only by the baryon density in the Universe. The dispersion in the available cloud composition observations exceeds the errors of individual measurements. This may indicate that there are mechanisms of the change in the composition of matter in the Universe after the completion of Big Bang nucleosynthesis. We have calculated the destruction and production rates of light isotopes (D, 3He, 4He) under the influence of photonuclear reactions triggered by the gamma-ray emission from active galactic nuclei (AGNs). We investigate the destruction and production of light elements depending on the spectral characteristics of the gamma-ray emission. We show that in comparison with previous works, taking into account the influence of spectral hardness on the photonuclear reaction rates can increase the characteristic radii of influence of the gamma-ray emission from AGNs by a factor of 2-8. The high gamma-ray luminosities of AGNs observed in recent years increase the previous estimates of the characteristic radii by two orders of magnitude. This may suggest that the influence of the emission from AGNs on the change in the composition of the medium in the immediate neighborhood (the host galaxy) has been underestimated.Comment: 13 pages, 13 figures, 3 table

Mammographic density and epithelial histopathologic markers

<p>Abstract</p> <p>Background</p> <p>We explored the association of mammographic density, a breast cancer risk factor, with hormonal and proliferation markers in benign tissue from tumor blocks of pre-and postmenopausal breast cancer cases.</p> <p>Methods</p> <p>Breast cancer cases were recruited from a case-control study on breast density. Mammographic density was assessed on digitized prediagnostic mammograms using a computer-assisted method. For 279 participants of the original study, we obtained tumor blocks and prepared tissue microarrays (TMA), but benign tissue cores were only available for 159 women. The TMAs were immunostained for estrogen receptor alpha (ERα) and beta (ERβ), progesterone receptor (PR), HER2/neu, Ki-67, and Proliferating Cell Nuclear Antigen (PCNA). We applied general linear models to compute breast density according to marker expression.</p> <p>Results</p> <p>A substantial proportion of the samples were in the low or no staining categories. None of the results was statistically significant, but women with PR and ERβ staining had 3.4% and 2.4% higher percent density. The respective values for Caucasians were 5.7% and 11.6% but less in Japanese women (3.5% and -1.1%). Percent density was 3.4% higher in women with any Ki-67 staining and 2.2% in those with positive PCNA staining.</p> <p>Conclusion</p> <p>This study detected little evidence for an association between mammographic density and expression of steroid receptors and proliferation markers in breast tissue, but it illustrated the problems of locating tumor blocks and benign breast tissue samples for epidemiologic research. Given the suggestive findings, future studies examining estrogen effects in tissue, cell proliferation, and density in the breast may be informative.</p

High-risk mammographic parenchymal patterns and anthropometric measures: a case–control study

Mammographic parenchymal patterns are related to breast cancer risk and are also affected by anthropometric measure. We carried out a case–control study comprising 200 cases with high-risk (P2 and DY) mammographic parenchymal pattern and 200 controls with low-risk (N1 and P1) patterns in order to investigate the effect of body size and shape and breast size on mammographic patterns. Women in the highest quartile of body mass index (BMI) distribution were significantly less likely to have a high-risk pattern (odds ratio (OR) = 0.21, 95% confidence interval (CI) 0.08–0.52, P-value for trend = 0.001) compared to those in the lowest quartile. Relative to women with a waist to hip ratio (WHR) of less than 0.75, the OR of having a high-risk pattern in women with a WHR greater than 0.80 was 0.30 (95% CI 0.14–0.63). Breast size as measured by cup size was significantly and negatively related to high-risk pattern. Our study indicates that both BMI and WHR are negatively associated with high-risk patterns. However, both phenomena are associated with increased risk of breast cancer in post-menopausal women. This negative confounding of two positive risk factors means that the effect of parenchymal patterns on risk will tend to be underestimated when not adjusted for BMI and WHR and vice versa. Thus we may have underestimated the importance of BMI and mammographic parenchymal patterns in the past. Further studies are needed to determine a measure of parenchymal density that is independent of anthropometric measures and breast size. © 1999 Cancer Research Campaig

Percentage density, Wolfe's and Tabár's mammographic patterns: agreement and association with risk factors for breast cancer

INTRODUCTION: The purpose of this report was to classify mammograms according to four methods and to examine their agreement and their relationship to selected risk factors for breast cancer. METHOD: Mammograms and epidemiological data were collected from 987 women, aged 55 to 71 years, attending the Norwegian Breast Cancer Screening Program. Two readers each classified the mammograms according to a quantitative method (Cumulus or Madena software) and one reader according to two qualitative methods (Wolfe and Tabár patterns). Mammograms classified in the reader-specific upper quartile of percentage density, Wolfe's P2 and DY patterns, or Tabár's IV and V patterns, were categorized as high-risk density patterns and the remaining mammograms as low-risk density patterns. We calculated intra-reader and inter-reader agreement and estimated prevalence odds ratios of having high-risk mammographic density patterns according to selected risk factors for breast cancer. RESULTS: The Pearson correlation coefficient was 0.86 for the two quantitative density measurements. There was moderate agreement between the Wolfe and Tabár classifications (Kappa = 0.51; 95% confidence interval 0.46 to 0.56). Age at screening, number of children and body mass index (BMI) showed a statistically significant inverse relationship with high-risk density patterns for all four methods (all P < 0.05). After adjustment for percentage density, the Wolfe classification was not associated with any of the risk factors for breast cancer, whereas the association with number of children and BMI remained statistically significant for the Tabár classification. Adjustment for Wolfe or Tabár patterns did not alter the associations between these risk factors and percentage mammographic density. CONCLUSION: The four assessments methods seem to capture the same overall associations with risk factors for breast cancer. Our results indicate that the quantitative methods convey additional information over the qualitative methods

Consensus-based guidelines for Video EEG monitoring in the pre-surgical evaluation of children with epilepsy in the UK

PURPOSE: Paediatric Epilepsy surgery in the UK has recently been centralised in order to improve expertise and quality of service available to children. Video EEG monitoring or telemetry is a highly specialised and a crucial component of the pre-surgical evaluation. Although many Epilepsy Monitoring Units work to certain standards, there is no national or international guideline for paediatric video telemetry. METHODS: Due to lack of evidence we used a modified Delphi process utilizing the clinical and academic expertise of the clinical neurophysiology sub-specialty group of Children’s Epilepsy Surgical Service (CESS) centres in England and Wales. This process consisted of the following stages I: Identification of the consensus working group, II: Identification of key areas for guidelines, III: Consensus practice points and IV: Final review. Statements that gained consensus (median score of either 4 or 5 using a five-point Likerttype scale) were included in the guideline. RESULTS: Two rounds of feedback and amendments were undertaken. The consensus guidelines includes the following topics: referral pathways, neurophysiological equipment standards, standards of recording techniques, with specific emphasis on safety of video EEG monitoring both with and without drug withdrawal, a protocol for testing patient’s behaviours, data storage and guidelines for writing factual reports and conclusions. All statements developed received a median score of 5 and were adopted by the group. CONCLUSIONS: Using a modified Delphi process we were able to develop universally-accepted video EEG guidelines for the UK CESS. Although these recommendations have been specifically developed for the pre-surgical evaluation of children with epilepsy, it is assumed that most components are transferable to any paediatric video EEG monitoring setting

Sex steroids, growth factors and mammographic density: a cross-sectional study of UK postmenopausal Caucasian and Afro-Caribbean women

INTRODUCTION: Sex steroids, insulin-like growth factors (IGFs) and prolactin are breast cancer risk factors but whether their effects are mediated through mammographic density, one of the strongest risk factors for breast cancer, is unknown. If such a hormonal basis of mammographic density exists, hormones may underlie ethnic differences in both mammographic density and breast cancer incidence rates. METHODS: In a cross-sectional study of 270 postmenopausal Caucasian and Afro-Caribbean women attending a population-based breast screening service in London, UK, we investigated whether plasma biomarkers (oestradiol, oestrone, sex hormone binding globulin (SHBG), testosterone, prolactin, leptin, IGF-I, IGF-II and IGF binding protein 3 (IGFBP3)) were related to and explained ethnic differences in mammographic percent density, dense area and nondense area, measured in Cumulus using the threshold method. RESULTS: Mean levels of oestrogens, leptin and IGF-I:IGFBP3 were higher whereas SHBG and IGF-II:IGFBP3 were lower in Afro-Caribbean women compared with Caucasian women after adjustment for higher mean body mass index (BMI) in the former group (by 3.2 kg/m(2) (95% confidence interval (CI): 1.8, 4.5)). Age-adjusted percent density was lower in Afro-Caribbean compared with Caucasian women by 5.4% (absolute difference), but was attenuated to 2.5% (95% CI: -0.2, 5.1) upon BMI adjustment. Despite ethnic differences in biomarkers and in percent density, strong ethnic-age-adjusted inverse associations of oestradiol, leptin and testosterone with percent density were completely attenuated upon adjustment for BMI. There were no associations of IGF-I, IGF-II or IGFBP3 with percent density or dense area. We found weak evidence that a twofold increase in prolactin and oestrone levels were associated, respectively, with an increase (by 1.7% (95% CI: -0.3, 3.7)) and a decrease (by 2.0% (95% CI: 0, 4.1)) in density after adjustment for BMI. CONCLUSIONS: These findings suggest that sex hormone and IGF levels are not associated with BMI-adjusted percent mammographic density in cross-sectional analyses of postmenopausal women and thus do not explain ethnic differences in density. Mammographic density may still, however, be influenced by much higher premenopausal hormone levels