MicroRNA-433 Dampens Glucocorticoid Receptor Signaling, Impacting Circadian Rhythm and Osteoblastic Gene Expression

FUNDING This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [AR44877]; the National Institutes for Dental and Craniofacial Research [5T90DE21989]; a Grant-in-Aid award from the American Society for Bone and Mineral Research; the UConn Health Center Research Advisory council; and the Center for Molecular Medicine at UConn Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Peer reviewedPublisher PD

Issues for computer modelling of room acoustics in non-concert hall settings

The basic principle of common room acoustics computer models is the energy-based geometrical room acoustics theory. The energy-based calculation relies on the averaging effect provided when there are many reflections from many different directions, which is well suited for large concert halls at medium and high frequencies. In recent years computer modelling has become an established tool in architectural acoustics design thanks to the advance in computing power and improved understanding of the modelling accuracy. However concert hall is only one of many types of built environments that require good acoustic design. Increasingly computer models are being sought for non-concert hall applications, such as in small rooms at low frequencies, flat rooms in workplace surroundings, and long enclosures such as underground stations. In these built environments the design issues are substantially difference from that of concert halls and in most cases the common room acoustics models will needed to be modified or totally re-formulated in order to deal with these new issues. This paper looks at some examples of these issues. In workplace environments we look at the issues of directional propagation and volume scattering by furniture and equipment instead of the surface scattering that is common assumed in concert hall models. In small rooms we look at the requirement of using wave models, such as boundary element models, or introducing phase information into geometrical room acoustics models to determine wave behaviours. Of particular interest is the ability of the wave models to provide phase information that is important not only for room modes but for the construction of impulse response for auralisation. Some simulated results using different modelling techniques will be presented to illustrate the problems and potential solutions

Sound fields near building facades: comparison of finite and semi-infinite reflectors on a rigid ground plane

The sound field in front of, and close to a building facade is relevant to the measurement and prediction of environmental noise and sound insulation. For simplicity it is often assumed that the facade can be treated as a semi-infinite reflector, however in the low-frequency range (50–200 Hz) this is no longer appropriate as the wavelengths are similar or larger than the facade dimensions. Scale model measurements and predictions using integral equation methods have been used to investigate the effect of diffraction on the sound field in front of finite size reflectors. For the situation that is commonly encountered in front of building facades, the results indicate that diffraction effects are only likely to be significant in the low-frequency range (50–200 Hz) when the façade dimensions are less than 5 m. This assumes that there is a point source close to the ground and microphones at a height of 1.2 or 1.5 m, at a distance between 1 and 2 m in front of the façade. © 2008 Elsevier Ltd. All rights reserved

Systematic alteration of ATAC-seq for profiling open chromatin in cryopreserved nuclei preparations from livestock tissues.

The use of Assay for Transposase-Accessible Chromatin (ATAC-seq) to profile chromatin accessibility has surged over the past years, but its applicability to tissues has been very limited. With the intent of preserving nuclear architecture during long-term storage, cryopreserved nuclei preparations from chicken lung were used to optimize ATAC-seq. Sequencing data were compared with existing DNase-seq, ChIP-seq, and RNA-seq data to evaluate library quality, ultimately resulting in a modified ATAC-seq method capable of generating high quality chromatin accessibility data from cryopreserved nuclei preparations. Using this method, nucleosome-free regions (NFR) identified in chicken lung overlapped half of DNase-I hypersensitive sites, coincided with active histone modifications, and specifically marked actively expressed genes. Notably, sequencing only the subnucleosomal fraction dramatically improved signal, while separation of subnucleosomal reads post-sequencing did not improve signal or peak calling. The broader applicability of this modified ATAC-seq technique was tested using cryopreserved nuclei preparations from pig tissues, resulting in NFR that were highly consistent among biological replicates. Furthermore, tissue-specific NFR were enriched for binding motifs of transcription factors related to tissue-specific functions, and marked genes functionally enriched for tissue-specific processes. Overall, these results provide insights into the optimization of ATAC-seq and a platform for profiling open chromatin in animal tissues

Primary osteoblast-like cells from patients with end-stage kidney disease reflect gene expression, proliferation, and mineralization characteristics ex vivo.

Osteocytes regulate bone turnover and mineralization in chronic kidney disease. As osteocytes are derived from osteoblasts, alterations in osteoblast function may regulate osteoblast maturation, osteocytic transition, bone turnover, and skeletal mineralization. Thus, primary osteoblast-like cells were cultured from bone chips obtained from 24 pediatric ESKD patients. RNA expression in cultured cells was compared with RNA expression in cells from healthy individuals, to RNA expression in the bone core itself, and to parameters of bone histomorphometry. Proliferation and mineralization rates of patient cells were compared with rates in healthy control cells. Associations were observed between bone osteoid accumulation, as assessed by bone histomorphometry, and bone core RNA expression of osterix, matrix gla protein, parathyroid hormone receptor 1, and RANKL. Gene expression of osteoblast markers was increased in cells from ESKD patients and signaling genes including Cyp24A1, Cyp27B1, VDR, and NHERF1 correlated between cells and bone cores. Cells from patients with high turnover renal osteodystrophy proliferated more rapidly and mineralized more slowly than did cells from healthy controls. Thus, primary osteoblasts obtained from patients with ESKD retain changes in gene expression ex vivo that are also observed in bone core specimens. Evaluation of these cells in vitro may provide further insights into the abnormal bone biology that persists, despite current therapies, in patients with ESKD

Estimating the public health impact of the effect of herpes simplex virus suppressive therapy on plasma HIV-1 viral load.

OBJECTIVE: Trials of herpes simplex virus (HSV) suppressive therapy among HSV-2/HIV-1-infected individuals have reported an impact on plasma HIV-1 viral loads (PVLs). Our aim was to estimate the population-level impact of suppressive therapy on female-to-male HIV-1 sexual transmission. DESIGN AND METHODS: By comparing prerandomization and postrandomization individual-level PVL data from the first two HSV suppressive therapy randomized controlled trials in sub-Saharan Africa, we estimated the effect of treatment on duration of asymptomatic infection and number of HIV-1 transmission events for each trial. RESULTS: Assuming that a reduction in PVL is accompanied by an increased duration of HIV-1 asymptomatic infection, 4-6 years of HSV suppressive therapy produce a 1-year increase in the duration of this stage. To avert one HIV-1 transmission requires 8.8 [95% confidence interval (CI), 5.9-14.9] and 11.4 (95% CI, 7.8-27.5) women to be treated from halfway through their HIV-1 asymptomatic period, using results from Burkina Faso and South African trials, respectively. Regardless of the timing of treatment initiation, 51.6 (95% CI, 30.4-137.0) and 66.5 (95% CI, 36.7-222.6) treatment-years are required to avert one HIV-1 infection. Distributions of set-point PVL values from sub-Saharan African populations suggest that unintended adverse consequences of therapy at the population level (i.e. increased HIV-1 transmission due to increased duration of infection) are unlikely to occur in these settings. CONCLUSION: HSV suppressive therapy may avert relatively few HIV-1 transmission events per person-year of treatment. Its use as a prevention intervention may be limited; however, further research into its effect on rate of CD4 cell count decline and the impact of higher dosing schedules is warranted

Genetic variation exists for telomeric array organization within and among the genomes of normal, immortalized, and transformed chicken systems

This study investigated telomeric array organization of diverse chicken genotypes utilizing in vivo and in vitro cells having phenotypes with different proliferation potencies. Our experimental objective was to characterize the extent and nature of array variation present to explore the hypothesis that mega-telomeres are a universal and fixed feature of chicken genotypes. Four different genotypes were studied including normal (UCD 001, USDA-ADOL Line 0), immortalized (DF-1), and transformed (DT40) cells. Both cytogenetic and molecular approaches were utilized to develop an integrated view of telomeric array organization. It was determined that significant variation exists within and among chicken genotypes for chromosome-specific telomeric array organization and total genomic-telomeric sequence content. Although there was variation for mega-telomere number and distribution, two mega-telomere loci were in common among chicken genetic lines (GGA 9 and GGA W). The DF-1 cell line was discovered to maintain a complex derivative karyotype involving chromosome fusions in the homozygous and heterozygous condition. Also, the DF-1 cell line was found to contain the greatest amount of telomeric sequence per genome (17%) as compared to UCD 001 (5%) and DT40 (1.2%). The chicken is an excellent model for studying unique and universal features of vertebrate telomere biology, and characterization of the telomere length variation among genotypes will be useful in the exploration of mechanisms controlling telomere length maintenance in different cell types having unique phenotypes

Qualitative protocol for understanding the contribution of Australian policy in the urban planning, justice, energy and environment sectors to promoting health and health equity

Introduction: A well-established body of literature demonstrates that health and equity are strongly influenced by the consequences of governments’ policy and resultant actions (or inactions) outside the health sector. Consequently, the United Nations, and its agency the WHO, have called for national leadership and whole-of-government action to understand and address the health impacts of policies in all sectors. This research responds to that call by investigating how policymaking in four sectors—urban planning, justice, energy and environment—may influence the social determinants of health and health equity (SDH/HE). Methods and analysis: The research design is informed by a critical qualitative approach. Three successive stages are included in the design. The first involves analysing all strategic policy documents and selected legislative documents from the four sectors (n=583). The document analysis is based on a coding framework developed to identify alignment between the documents and the SDH/HE. Two policies that demonstrate good practice in regard to SDH/HE will be selected from each sector during the second stage for embedded case study analysis (total n=8). This is intended to illuminate which factors have supported recognition and action on SDH/HE in the selected policies. The third stage involves progressive theoretical integration and development to understand political and institutional facilitators and barriers to action on SDH/HE, both within and between sectors. Ethics and dissemination: The research will provide much needed evidence about how coherent whole-of-government action on SDH/HE can be advanced and contribute knowledge about how health-enhancing policy activity in the four sectors may be optimised. Learnings from the research will be shared via a project advisory group, policy briefings, academic papers, conference presentations and research symposia. Ethics approval has been secured for the embedded case studies, which involve research participants