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Summary Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses. [ABSTRACT FROM AUTHOR]

This article explores the ways in which ‘gangsta’ English features are deployed, evaluated and adopted in two types of social media, the web forum and Twitter, within the domains of hip hop culture and football (soccer) culture, from the dual perspective of authenticity and normativity. Empirically, we aim to break new ground by investigating the intricate interconnections between two social media formats and combining two highly popular but previously seldom connected cultural forms—football and hip hop. Our theoretical aim is to contribute to the current debate on authenticity, normativity, popular culture and social media, and the complex ways in which they are connected. We focus, first, on the Twitter writing of the Finnish footballer Mikael Forssell, specifically his uses of non-Standard English and references to hip hop culture and rap music, and second, on the ways in which Forssell’s stylized writing elicits normatively oriented metapragmatic commentaries, i.e., meta-level discussion, on a major Finnish football discussion forum. Of particular interest here is the emically emerging category of ‘gangsta’ English and its perceived (in)authenticity—when used by Forssell and two other (‘White’) middle-class Finnish footballers. Drawing on the frameworks of authenticity and sociolinguistic superdiversity, we foreground the tension between purist normativity and playful appropriation online. Our discussion highlights the unpredictability of the connections between language use, (popular) cultural forms, ethnicity, country of origin, and the complexity of mediation across online and offline sites of social action. [ABSTRACT FROM AUTHOR]

Cardiac allograft rejection is currently monitored indirectly by evaluating graft function with clinical and laboratory parameters, but also histologically by evaluating endomyocardial biopsies (EMB) at regular intervals. EMB-sampling is invasive, and may result in complications, such as bleeding, pneumothorax, or cardiac tamponade. Furthermore, the biopsies represent only very small local histological area. As less invasive and more sensitive methods for detecting allograft injury and rejection are warranted, and donor-derived cell-free DNA (dd-cfDNA) detection from peripheral blood has been previously proposed as a feasible alternative method. We have initiated a prospective clinical trial ("EMBIO") in order to validate the sensitivity and specificity of cardiac allograft recipient peripheral blood liquid biopsy. We perform 25-35 cardiac transplantations yearly, and all transplant recipients operated in Helsinki University Hospital, will be recruited into the EMBIO-trial. Current number of recruited transplant recipients this year is 23. The study population is treated and followed up according to the local clinical protocol. With every routine EMB-sample, an extra study sample is taken for RNA-sequencing and an extra blood sample is taken for dd-cfDNA analysis. Patients follow a preplanned biopsy protocol: EMB samples are taken at 2, 4, 6, 8, 10, and 12 weeks, and 4, 5, 6, 8, 10, and 12 months after the transplantation. In addition to the biopsy protocol, a blood sample is taken 24 h after transplantation for dd-cfDNA analysis. The method of cfDNA analysis has just recently been added to the routine practice of our hospital's core laboratory service, and by 15.10.19, the samples of the first 5 patients have been analyzed. By March 2020, we expect to have a full sample analysis performed on the first 20 patients up until the 6-month follow-up, and another 10-20 patient on earlier timepoints. We will perform full RNAseq analysis of the EMB and we will compare the results of cfDNA to the RNA profile, and the histological evaluation of the biopsies. We expect to be able to present detailed pattern of dd-cfDNA kineticts early after transplantation, and its correlation to possible rejection episodes. We also will present RNAseq data on several early timepoints for at least 20 patients. [ABSTRACT FROM AUTHOR]

Fast progress of the next generation sequencing (NGS) technology has allowed global transcriptional profiling and genome-wide mapping of transcription factor binding sites in various cellular contexts. However, limited number of replicates and high amount of data processing may weaken the significance of the findings. Comparative analyses of independent data sets acquired in the different laboratories would greatly increase the validity of the data. Runx2 is the key transcription factor regulating osteoblast differentiation and bone formation. We performed a comparative analysis of three published Runx2 data sets of chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) analysis in osteoblasts from mouse and human origin. Moreover, we assessed the similarity of the corresponding transcription data of these studies available online. The ChIP-seq data analysis confirmed general features of Runx2 binding, including location at genic vs intergenic regions and abundant Runx2 binding on promoters of the highly expressed genes. We also found high frequency of Runx2 DNA binding without a consensus Runx2 motif at the binding site. Importantly, mouse and human Runx2 showed moderately similar binding patterns in terms of peak-associated closest genes and their associated genomic ontology (GO) pathways. Accordingly, the gene expression profiles were highly similar and osteoblastic phenotype was prominent in the differentiated stage in both species. In conclusion, ChIP-seq method shows good reproducibility in the context of mature osteoblasts, and mouse and human osteoblast models resemble each other closely in Runx2 binding and in gene expression profiles, supporting the use of these models as adequate tools in studying osteoblast differentiation. [ABSTRACT FROM AUTHOR]

Grid stability becomes an issue when incorporating renewable distribution generation into an electrical grid due to voltage fluctuations. This work presents an innovative solution which assists grid planners in carrying out technical and economic analysis of future grids and in taking decisions based on it. A set of tools allows the determination of the renewable energy sources and energy storage systems impact to a given grid concerning technical and economic indicators. Using these tools, a study was conducted comparing model predictive control with photovoltaics-curtailment, volt-watt and volt-var methods for the control of photovoltaics and energy storage power in an existing grid. Some highlights of the analysis are: (i) the given grid supports maximal photovoltaics penetration level of 120% without exceeding the ±10 % voltage level limits; (ii) the model predictive control method aiming at the minimization of power exchange in a grid with 60% storage penetration allowed significant increase of photovoltaics penetration to 190% and reduced the maximum voltage level to 1.089pu; (iii) a user-centered design and development of the interface for grid planners resulted in a system usability scale score of 63.9. The tools enable the grid planner to take decisions when planning the future grid. • Method to analyze storage impact at various levels of photovoltaic penetration. • Tool for grid planners to assure grid stability for increasing photovoltaics. • Planning tool to avoid voltage violations due to high photovoltaic penetration. • Economic model to justify storage cost to increase photovoltaic hosting capacity. • User-centered tool to assist planning grid of the future with increasing renewables. [ABSTRACT FROM AUTHOR]

Cardiac allograft rejection is monitored by histological evaluation of surveillance endomyocardial biopsies (EMB). EMB is invasive and may result in complications, such as bleeding, pneumothorax, damage to tricuspid valve, or cardiac tamponade. Furthermore, the biopsies evaluated by pathologists represent only a very small local histological area and their analysis is imprecise due to inter-observer variance. Donor-derived cell-free DNA (dd-cfDNA) detection from peripheral blood has been previously proposed as a feasible alternative and less-invasive method. The purpose of this study is to validate the method of detecting dd-cfDNA in a prospective patient cohort. We have prospectively collected clinical data, EMB, and blood samples from all heart transplant recipients operated in our unit. Patients were treated with tacrolimus-based triple-drug immunosuppression including anti-thymocyteglobulin induction therapy. EMB samples were taken at 2, 4, 6, 8, 10, and 12 weeks, and 4, 5, 6, 8, 10, and 12 months after transplantation and subjected to histological evaluation. Simultaneously, selected single-nucleotide polymorphisms were determined from pre-biopsy peripheral blood samples, and the ratio of dd-cfDNA-to-recipient-cfDNA was calculated. With every EMB sampling, an extra study sample is taken for RNA-sequencing analysis. We have collected data and samples from 52 consecutive heart transplant recipients with the mean follow-up of 19.2±9.2 months and performed 399 dd-cfDNA quantitations. Of these, 10 results were excluded from the analyses due to multiorgan transplantation (heart+kidney), and 5 results were discarded due to insufficient corresponding EMB sample. Our cohort consists of 297 samples with G0R, 97 with G1R, 8 with G2R, and one with G3R histopathological rejection. The corresponding dd-cfDNA values were 0.16%±0.216% for G0R, 0.16%±0.217% for G1R, and 0.28%±0.162% for G2R/G3R. The predictive value of dd-cfDNA for acute rejection failed to reach statistical significance. The novel detection method for dd-cfDNA shows promising preliminary results with higher values in more severe histopathological rejection classes. The limitations of our current results stem from the low numbers of G2R/G3R rejections. [ABSTRACT FROM AUTHOR]

• Juice from grass silage was produced by a twin-screw press. • The silage juice was successfully incorporated into liquid feed for growing pigs. • Meat quality was not negatively affected by silage juice inclusion. • Gut microbiome of the pigs was not altered in response to silage juice intake. • Silage juice provides a novel sustainable feed ingredient for pork production. Traditionally grass has been considered a suitable feed only for ruminants. Due to global challenges related to growing human population, sustainable feed materials for pigs are actively searched and grasses as a high yielding biomass have been seen as an interesting addition to pig feeds. The digestible nutrients in grasses are embedded in a fibre matrix not digestible to pigs, but suitable processing could alleviate this. The aim of the present study was to evaluate whether silage juice could provide a new sustainable diet ingredient for fattening pigs. Grass silage was fractionated with a twin-screw press to liquid and solid fractions. The silage juice was included into liquid feed of 112 fattening pigs from 62 kg live weight until slaughter (124 kg live weight) and compared to 96 pigs on a conventional control diet. Feed allowance was ad libitum until it reached 33.6 MJ net energy day−1 per pig which was kept as the maximum feed allowance until slaughter. The average daily gain of all the pigs was over 1000 g day−1 in the experimental period but no difference between silage juice fed and control group was found. The feed conversion ratio was, as expected, higher in barrows than gilts, but no difference was found between the two treatment groups. Variation in silage juice dry matter content during the experimental period may have led to a lower dry matter intake of silage juice fed pigs. Gilts had statistically significantly higher meat percentage than barrows in both treatments, but no difference was found between the treatment groups. Meat quality (pH, colour, drip loss and sensory analyses) results were similar in both treatment groups. For gut microbiota, no statistically significant differences were found in any of the bacterial families studied (Actinobacteriota, Bacteroidota, Firmicutes, Deferrivacterota, Spirochaetota, Minor Phyla). In conclusion, silage juice is a potential feed ingredient in liquid feed for pigs. Microbiological data indicates that silage juice does not cause gastrointestinal microbiota imbalance in pigs. [ABSTRACT FROM AUTHOR]

Data from 207 production trials (998 treatment means) were used to study the effects of animal and dietary characteristics on the efficiency of N utilization for milk protein production, and on fecal N, urinary N, and total manure N output. The average efficiency of transferring dietary N to milk N (MNE; milk N/N intake) was 277 (SD = 36.0) g/kg. Nitrogen efficiency was poorly related to milk yield. Dietary concentrations of crude protein (CP) and protein balance in the rumen (PBV) were the best single predictors of MNE. Dietary CP concentration explained variation in MNE better than did N intake. Bivariate models with PBV or metabolizable protein (MP) explained the variation better than CP alone. The effects of protein feeding parameters on MNE were consistent among data subsets from studies investigating the effects of the amount and protein concentration of concentrate supplement, silage digestibility, silage fermentation quality, or substitution of grass silage with legume silage. The model with total dry matter and N intakes as independent variables explained fecal, urinary, and total manure N output more precisely than N intake alone. The model of fecal N output suggested that the true digestibility of dietary N was 0.91, and that metabolic and endogenous N was the major component in fecal N. The proportion of urine N in manure N was strongly related to dietary CP concentration. Including the concentration of dietary carbohydrates only slightly improved the models, indicating that the most effective strategy to improve MNE and to decrease N losses in manure, especially in urine, is to avoid feeding diets with excessively high CP concentration and especially excess ruminally degradable CP. [ABSTRACT FROM AUTHOR]