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BackgroundInterphase chromosomes adopt a hierarchical structure, and recent data have characterized their chromatin organization at very different scales, from sub-genic regions associated with DNA-binding proteins at the order of tens or hundreds of bases, through larger regions with active or repressed chromatin states, up to multi-megabase-scale domains associated with nuclear positioning, replication timing and other qualities. However, we have lacked detailed, quantitative models to understand the interactions between these different strata.ResultsHere we collate large collections of matched locus-level chromatin features and Hi-C interaction data, representing higher-order organization, across three human cell types. We use quantitative modeling approaches to assess whether locus-level features are sufficient to explain higher-order structure, and identify the most influential underlying features. We identify structurally variable domains between cell types and examine the underlying features to discover a general association with cell-type-specific enhancer activity. We also identify the most prominent features marking the boundaries of two types of higher-order domains at different scales: topologically associating domains and nuclear compartments. We find parallel enrichments of particular chromatin features for both types, including features associated with active promoters and the architectural proteins CTCF and YY1.ConclusionsWe show that integrative modeling of large chromatin dataset collections using random forests can generate useful insights into chromosome structure. The models produced recapitulate known biological features of the cell types involved, allow exploration of the antecedents of higher-order structures and generate testable hypotheses for further experimental studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0661-x) contains supplementary material, which is available to authorized users.  相似文献   
3.
The effective management of leachables in pharmaceutical products is a critical aspect of their development. This can be facilitated if extractables information on the materials used in a packaging or delivery system is available to assist companies in selecting materials that will be compatible with the drug product formulation and suitable for the intended use. The Extractables and Leachables Safety Information Exchange (ELSIE) materials working group developed and executed a comprehensive extraction study protocol that included a number of extraction solvents, extraction techniques, and a variety of analytical techniques. This was performed on two test materials, polyethylene (PE) and polyvinyl chloride (PVC), that were selected due to their common use in pharmaceutical packaging. The purpose of the study was to investigate if the protocol could be simplified such that (i) a reduced number or even a single extraction technique could be used and (ii) a reduced number of solvents could be used to obtain information that is useful for material selection regardless of product type. Results indicate that, at least for the PVC, such reductions are feasible. Additionally, the studies indicate that levels of extractable elemental impurities in the two test materials were low and further confirm the importance of using orthogonal analytical detection techniques to gain adequate understanding of extraction profiles.KEY WORDS: extractables, extraction technique, polyethylene, polyvinyl chloride  相似文献   
4.
Volunteers are increasingly being recruited into citizen science projects to collect observations for scientific studies. An additional goal of these projects is to engage and educate these volunteers. Thus, there are few barriers to participation resulting in volunteer observers with varying ability to complete the project’s tasks. To improve the quality of a citizen science project’s outcomes it would be useful to account for inter-observer variation, and to assess the rarely tested presumption that participating in a citizen science projects results in volunteers becoming better observers. Here we present a method for indexing observer variability based on the data routinely submitted by observers participating in the citizen science project eBird, a broad-scale monitoring project in which observers collect and submit lists of the bird species observed while birding. Our method for indexing observer variability uses species accumulation curves, lines that describe how the total number of species reported increase with increasing time spent in collecting observations. We find that differences in species accumulation curves among observers equates to higher rates of species accumulation, particularly for harder-to-identify species, and reveals increased species accumulation rates with continued participation. We suggest that these properties of our analysis provide a measure of observer skill, and that the potential to derive post-hoc data-derived measurements of participant ability should be more widely explored by analysts of data from citizen science projects. We see the potential for inferential results from analyses of citizen science data to be improved by accounting for observer skill.  相似文献   
5.
Earlier research has revealed that the ndh loci have been pseudogenized, truncated, or deleted from most orchid plastomes sequenced to date, including in all available plastomes of the two most species-rich subfamilies, Orchidoideae and Epidendroideae. This study sought to resolve deeper-level phylogenetic relationships among major orchid groups and to refine the history of gene loss in the ndh loci across orchids. The complete plastomes of seven orchids, Oncidium sphacelatum (Epidendroideae), Masdevallia coccinea (Epidendroideae), Sobralia callosa (Epidendroideae), Sobralia aff. bouchei (Epidendroideae), Elleanthus sodiroi (Epidendroideae), Paphiopedilum armeniacum (Cypripedioideae), and Phragmipedium longifolium (Cypripedioideae) were sequenced and analyzed in conjunction with all other available orchid and monocot plastomes. Most ndh loci were found to be pseudogenized or lost in Oncidium, Paphiopedilum and Phragmipedium, but surprisingly, all ndh loci were found to retain full, intact reading frames in Sobralia, Elleanthus and Masdevallia. Character mapping suggests that the ndh genes were present in the common ancestor of orchids but have experienced independent, significant losses at least eight times across four subfamilies. In addition, ndhF gene loss was correlated with shifts in the position of the junction of the inverted repeat (IR) and small single-copy (SSC) regions. The Orchidaceae have unprecedented levels of homoplasy in ndh gene presence/absence, which may be correlated in part with the unusual life history of orchids. These results also suggest that ndhF plays a role in IR/SSC junction stability.  相似文献   
6.

Introduction

Breast cancer is a complex heterogeneous disease and is a leading cause of death in women. Early diagnosis and monitoring progression of breast cancer are important for improving prognosis. The aim of this study was to identify protein biomarkers in urine for early screening detection and monitoring invasive breast cancer progression.

Method

We performed a comparative proteomic analysis using ion count relative quantification label free LC-MS/MS analysis of urine from breast cancer patients (n = 20) and healthy control women (n = 20).

Results

Unbiased label free LC-MS/MS-based proteomics was used to provide a profile of abundant proteins in the biological system of breast cancer patients. Data analysis revealed 59 urinary proteins that were significantly different in breast cancer patients compared to the normal control subjects (p<0.05, fold change >3). Thirty-six urinary proteins were exclusively found in specific breast cancer stages, with 24 increasing and 12 decreasing in their abundance. Amongst the 59 significant urinary proteins identified, a list of 13 novel up-regulated proteins were revealed that may be used to detect breast cancer. These include stage specific markers associated with pre-invasive breast cancer in the ductal carcinoma in-situ (DCIS) samples (Leucine LRC36, MAST4 and Uncharacterized protein CI131), early invasive breast cancer (DYH8, HBA, PEPA, uncharacterized protein C4orf14 (CD014), filaggrin and MMRN2) and metastatic breast cancer (AGRIN, NEGR1, FIBA and Keratin KIC10). Preliminary validation of 3 potential markers (ECM1, MAST4 and filaggrin) identified was performed in breast cancer cell lines by Western blotting. One potential marker MAST4 was further validated in human breast cancer tissues as well as individual human breast cancer urine samples with immunohistochemistry and Western blotting, respectively.

Conclusions

Our results indicate that urine is a useful non-invasive source of biomarkers and the profile patterns (biomarkers) identified, have potential for clinical use in the detection of BC. Validation with a larger independent cohort of patients is required in the following study.  相似文献   
7.

Background

Children with antisocial behaviour show deficits in the perception of emotional expressions in others that may contribute to the development and persistence of antisocial and aggressive behaviour. Current treatments for antisocial youngsters are limited in effectiveness. It has been argued that more attention should be devoted to interventions that target neuropsychological correlates of antisocial behaviour. This study examined the effect of emotion recognition training on criminal behaviour.

Methods

Emotion recognition and crime levels were studied in 50 juvenile offenders. Whilst all young offenders received their statutory interventions as the study was conducted, a subgroup of twenty-four offenders also took part in a facial affect training aimed at improving emotion recognition. Offenders in the training and control groups were matched for age, SES, IQ and lifetime crime level. All offenders were tested twice for emotion recognition performance, and recent crime data were collected after the testing had been completed.

Results

Before the training there were no differences between the groups in emotion recognition, with both groups displaying poor fear, sadness and anger recognition. After the training fear, sadness and anger recognition improved significantly in juvenile offenders in the training group. Although crime rates dropped in all offenders in the 6 months following emotion testing, only the group of offenders who had received the emotion training showed a significant reduction in the severity of the crimes they committed.

Conclusions

The study indicates that emotion recognition can be relatively easily improved in youths who engage in serious antisocial and criminal behavior. The results suggest that improved emotion recognition has the potential to reduce the severity of reoffending.  相似文献   
8.
The metatolic fate of silicone gel leaked from an intact or ruptured prosthesis is unknown. In this study, serum was blindly assayed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) for elemental silicon in 72 women with silicone gel breast implants and 55 control women (mean age 48 yr, both groups). Blood was drawn and processed using silicon-free materials. The mean silicon level in controls was 0.13±0.07 mg/L (range 0.06–0.35 mg/L), whereas in implant patients, the mean was significantly higher at 0.28±0.22 mg/L (range 0.06–0.87 mg/L) (P<0.01, Student'st-test with correction for unequal variances). Using the mean of the control group +2 SD as a cutoff for normal range (0.27 mg/L), 25/72 (34.7%) implant patients exceeded this value, compared with 2/55 (3.6%) controls. There was no significant correlation between past rupture of one or both implants, current rupture at the time of the blood draw, or the number of years with implants and silicon levels. The results suggest that serum silicon levels are elevated in many women with silicone gel breast implants. The chemical species involved and kinetics of this elevation remain to be determined.  相似文献   
9.
10.
Structural requirements for the activation of transducin by rhodopsin have been studied by site-specific mutagenesis of bovine rhodopsin. A variety of single amino acid replacements and amino acid insertions and deletions of varying sizes were carried out in the two cytoplasmic loops CD (amino acids 134-151) and EF (amino acids 231-252). Except for deletion mutant delta 137-150, all the mutants bound 11-cis-retinal and displayed normal spectral characteristics. Deletion mutant delta 236-239 in loop EF caused a 50% reduction of transducin activation, whereas deletion mutant delta 244-249 and the larger deletions in loop EF abolished transducin activation. An 8-amino acid deletion in the cytoplasmic loop CD as well as a replacement of 13 amino acids with an unrelated sequence showed no transducin activation. Several single amino acid substitutions also caused significant reduction in transducin activation. The conserved charged pair Glu-134/Arg-135 in the cytoplasmic loop CD was required for transducin activation; its reversal or neutralization abolished transducin activation. Three amino acid replacements in loop EF (S240A, T243V, and K248L) resulted in significant reduction in transducin activation. We conclude that 1) both the cytoplasmic loops CD and EF are required for transducin activation, and 2) effective functional interaction between rhodopsin and transducin involves relatively large peptide sequences in the cytoplasmic loops.  相似文献   
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