Abstract only
Covalent modifications of histone tails and protein domains that bind these epigenetic marks are essential components of the chromatin remodeling and gene expression machinery. The PHD ...(plant homeodomain) finger is found in many transcriptional regulators and chromatin‐associating complexes, however the overall biological role of this module remains unclear. Recently, it was found that a subset of PHD fingers recognizes histone H3 tri‐methylated at lysine 4 (H3K4me3). In this study, we characterize the binding specificity of the PHD finger family using a set of biochemical, crystallographic and spectroscopic approaches. We compare the crystal structures of the H3K4me3‐bound PHD fingers, identify the binding sites for methylated histone H3 tails by resonance perturbation analysis and mutagenesis, and measure the binding affinities by tryptophan fluorescence. Our results provide novel insight into the molecular mechanisms underlying the activity of the histone‐binding PHD fingers, and further our understanding on how the histone code is read.
The PHD (plant homeodomain) finger is found in many chromatin associated proteins however its function remains unclear. We found that a subset of PHD fingers targets tri‐methylated histone H3 ...(H3K4me3) tail and represents a novel family of effector proteins that recognize this epigenetic mark1,2. We have determined structures of the PHD fingers of ING (inhibitor of growth) tumor suppressors in complex with a histone H3K4me3 peptide and characterized their specificity toward post‐translationally modified histone tails. The H3K4me3 peptide is bound in an extended conformation in a deep and extensive binding site consisting of elements that are conserved among other PHD fingers. The trimethylammonium group of Lys 4 is recognized by aromatic residues of the domain, whereas the intermolecular hydrogen‐bonding and complementary surface interactions, involving five peptide residues, account for the PHD finger's high specificity and affinity. Substitution of the binding site residues disrupts H3K4me3 interaction in vitro and impairs the ability of ING to induce apoptosis, suggesting a novel tumor suppressive mechanism. Strong binding of yeast YNG PHD fingers indicates that the recognition of the H3K4me3 histone code is a general function of this protein family.
Supported by the NIH and AHA (CA113472, GM071424 and 0555561Z to T.G.K.).
New azahelicenes having interesting photophysical properties have been prepared in a four‐step sequence. These 7helicenocarbazoles are efficient blue luminophores, demonstrating the utility of gold ...catalysis in the preparation of advanced materials.
Shining blue: A four‐step sequence from commercial precursors, has allowed for the preparation of new azahelical 6‐5‐6‐6‐6‐5‐6 derivatives, which are efficient blue luminophores.
Over the years, the most common methods for monitoring reproductive health in cattle have varied from transrectal palpation to B-mode ultrasonography. Nowadays, some portable ultrasound equipment ...includes the Doppler mode. Therefore, the aim of this study was to compare the accuracy of the different methods to assess corpus luteum (CL) functionality.
In Experiment 1, 53 Holstein lactating cows undergoing a synchronization protocol were examined via transrectal palpation and B-mode scanning. Measurements for the largest diameter (LAD) and subjective size of CL (SCLS) were collected. Data were analyzed using correlation analysis and ROC Curves. In Experiment 2, 30 Holstein non-lactating cows with a CL were administered PGF2α and examined several times after injection, first in B-mode and then with Power Doppler. Measurements for LAD, CL area (CLA) and subjective and objective CL blood flow were collected. Blood samples were taken in both experiments to determine P4 concentration. Data were analyzed using correlation analysis and the GLM repeated measures test.
Results for Experiment 1 showed that LAD was more accurate than SCLS. In Experiment 2, CLA was the best measurement to assess CL function, although both subjective and objective CL blood flow offer accurate information 24 h after PGF2α administration.
Consequently, ultrasonography provides more accurate information about CL function than transrectal palpation. Although CLA seems to be an earlier indicator of luteal function than blood flow, 24 h after the onset of luteolysis, both parameters are valid.
Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic options. In the last decade, several omics studies have provided significant insights into the molecular ...mechanisms of these diseases. Nevertheless, data from different cohorts and pathologies are stored independently in public repositories and a unified resource is imperative to assist researchers in this field.
Here, we present Autoimmune Diseases Explorer ( https://adex.genyo.es ), a database that integrates 82 curated transcriptomics and methylation studies covering 5609 samples for some of the most common autoimmune diseases. The database provides, in an easy-to-use environment, advanced data analysis and statistical methods for exploring omics datasets, including meta-analysis, differential expression or pathway analysis.
This is the first omics database focused on autoimmune diseases. This resource incorporates homogeneously processed data to facilitate integrative analyses among studies.
Abstract
Background
Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome.
Methods
Paediatric and adult nephrologists ...contacted through European professional organizations entered data in an online form.
Results
Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0–60) years and at last follow-up 14.0 (0.1–70) years. In adults, height was normal with a mean (standard deviation) score of −0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients.
Conclusion
This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems.
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