Structural Insight into Chromatin Recognition by Multiple Domains of the Tumor Suppressor RBBP1

Retinoblastoma-binding protein 1 (RBBP1) is involved in gene regulation, epigenetic regulation, and disease processes. RBBP1 contains five domains with DNA-binding or histone-binding activities, but how RBBP1 specifically recognizes chromatin is still unknown. An AT-rich interaction domain (ARID) in RBBP1 was proposed to be the key region for DNA-binding and gene suppression. Here, we first determined the solution structure of a tandem PWWP-ARID domain mutant of RBBP1 after deletion of a long flexible acidic loop L12 in the ARID domain. NMR titration results indicated that the ARID domain interacts with DNA with no GC- or AT-rich preference. Surprisingly, we found that the loop L12 binds to the DNA-binding region of the ARID domain as a DNA mimic and inhibits DNA binding. The loop L12 can also bind weakly to the Tudor and chromobarrel domains of RBBP1, but binds more strongly to the DNA-binding region of the histone H2A-H2B heterodimer. Furthermore, both the loop L12 and DNA can enhance the binding of the chromobarrel domain to H3K4me3 and H4K20me3. Based on these results, we propose a model of chromatin recognition by RBBP1, which highlights the unexpected multiple key roles of the disordered acidic loop L12 in the specific binding of RBBP1 to chromatin.     

A Comparison of Bone Mineral Density and Its Predictors in HIV-Infected and HIV-Uninfected Older Men

ObjectiveBone health in older individuals with HIV infection has not been well studied. This study aimed to compare bone mineral density (BMD), trabecular bone score (TBS), and bone markers between HIV-infected men and age- and body mass index (BMI)-matched HIV-uninfected men aged ≥60 years. We investigated the associations of risk factors related to fracture with BMD, TBS, and bone markers in HIV-infected men.MethodsThis cross-sectional study included 45 HIV-infected men receiving antiretroviral therapy and 42 HIV-uninfected men. Medical history, BMD and TBS measurements, and laboratory tests related to bone health were assessed in all the participants. HIV-related factors known to be associated with bone loss were assessed in the HIV-infected men.ResultsThe mean BMD, TBS, and osteopenia or osteoporosis prevalence were similar among the cases and controls. The HIV-infected men had significantly higher mean N-terminal propeptide of type 1 procollagen and C-terminal cross-linking telopeptide of type I collagen levels. Stepwise multiple linear regression analysis demonstrated that low BMI (lumbar spine, P = .015; femoral neck, P = .018; and total hip, P = .005), high C-terminal cross-linking telopeptide of type I collagen concentration (total hip, P = .042; and TBS, P = .010), and low vitamin D supplementation (TBS, P = .035) were independently associated with low BMD and TBS.ConclusionIn older HIV-infected men with a low fracture risk, the mean BMD and TBS were similar to those of the age- and BMI-matched controls. The mean bone marker levels were higher in the HIV group. Traditional risk factors for fracture, including low BMI, high C-terminal cross-linking telopeptide of type I collagen level, and low vitamin D supplementation, were significant predictors of low BMD and TBS.     

An Efficient Regression Type Estimator in Survey Sampling

For the estimation of population mean in simple random sampling, an efficient regression-type estimator is proposed which is more efficient than the conventional regression estimator and hence than mean per unit estimator, ratio and product estimators and many other estimators proposed by various authors. Some numerical examples are included for illustration.     

Effects of local density and flower colour polymorphism on pollination and reproduction in the rewardless orchid Dactylorhiza sambucina (L.) Soò

The rewardless orchid Dactylorhiza sambucina shows a stable flower colour polymorphism, with both yellow- and red-flowered morphs growing sympatrically. Pollination biology and breeding system were investigated to examine the effects of density of plants, colour polymorphism, inflorescence dimension, and flower position within inflorescence on male and female reproductive success in three natural populations of D. sambucina. There were significant differences among sites in the number of pollinia removed and in fruit set per inflorescence. Number of removed pollinia and capsule production in D. sambucina were independent from flower and inflorescence size or flower position. As a whole, the red morphs showed the highest number of capsules produced, while the yellow morphs had the greatest male success. The relative male and female reproductive success were independent from plant density but were significantly correlated with the yellow morph frequency at the population level. Overall, our findings show that the contribution to the total reproductive success deriving from the two colour morphs does not conform with the predictions of negative frequency-dependent selection.     

Rates of small-scale species mobility in alvar limestone grassland

Abstract. Small-scale species frequency and cumulative species frequency were studied in four plots in limestone grassland of the Veronica spicata-Avenula pratensis association on Stora Alvaret on the Baltic island of Öland, Sweden. Species mobility was expressed as increase in cumulative species frequency in 20 subplots of 100 cm². Observed cumulative frequencies from 1985–1989 in all four plots, and from 1985–1995 in one plot were compared with values following from two null models, a ‘minimal mobility’ model and a random mobility model. In ca. 50 % of the cases the observed cumulative frequency was not significantly different from the random expectation. However, in many such cases the mean annual frequency was either very high or very low. Three ways of calculating the mobility rate are presented though only one is used: (observed cumulative frequency -lowest annual frequency) / expected cumulative frequency. Values × 100 range from 0 to 100. There were slight differences between the four plots which were interpreted in terms of differences in grazing intensity and soil depth. It is stressed that the idea of the Carousel model has never been meant to suggest that all species would show random mobility, which we now quantify, but that species differ in their mobility rate and that the mean rate is much higher than generally realized.     

Modela-r as a Froude and Strouhal dimensionless numbers combination for dynamic similarity in running

The aim of this study was to test the hypothesis that running at fixed fractions of Froude (Nfr) and Strouhal (Str) dimensionless numbers combinations induce dynamic similarity between humans of different sizes. Nineteen subjects ran in three experimental conditions, (i) constant speed, (ii) similar speed (Nfr) and (iii) similar speed and similar step frequency (Nfr and Str combination). In addition to anthropometric data, temporal, kinematic and kinetic parameters were assessed at each stage to measure dynamic similarity informed by dimensional scale factors and by the decrease of dimensionless mechanical parameter variability. Over a total of 54 dynamic parameters, dynamic similarity from scale factors was met for 16 (mean r=0.51), 32 (mean r=0.49) and 52 (mean r=0.60) parameters in the first, the second and the third experimental conditions, respectively. The variability of the dimensionless preceding parameters was lower in the third condition than in the others. This study shows that the combination of Nfr and Str, computed from the dimensionless energy ratio at the center of gravity (Modela-r) ensures dynamic similarity between different-sized subjects. The relevance of using similar experimental conditions to compare mechanical dimensionless parameters is also proved and will highlight the study of running techniques, or equipment, and will allow the identification of abnormal and pathogenic running patterns. Modela-r may be adapted to study other abilities requiring bounces in human or animal locomotion or to conduct investigations in comparative biomechanics.     

High frequency residues: A new set of signals for detectability studies of an X-ray imaging system

A new set of signals for studying detectability of an X-ray imaging system is presented. The results obtained with these signals are intended to complement the NEQ results.The signals are generated from line spread profiles by progressively removing their lower frequency components and the resulting high frequency residues (HFRs) form the set of signals to be used in detectability studies. Detectability indexes for these HFRs are obtained using a non-prewhitening (NPW) observer and a series of edge images are used to obtain the HFRs, the covariance matrices required by the NPW model and the MTF and NPS used in NEQ calculations. The template used in the model is obtained by simulating the processes of blurring and sampling of the edge images. Comparison between detectability indexes for the HFRs and NEQ are carried out for different acquisition techniques using different beam qualities and doses.The relative sensitivity shown by detectability indexes using HFRs is higher than that of NEQ, especially at lower doses. Also, the different observers produce different results at high doses: while the ideal Bayesian observer used by NEQ distinguishes between beam qualities, the NPW used with the HFRs produces no differences between them.Delta functions used in HFR are the opposite of complex exponential functions in terms of their support in the spatial and frequency domains. Since NEQ can be interpreted as detectability of these complex exponential functions, detectability of HFRs is presented as a natural complement to NEQ in the performance assessment of an imaging system.