Human TFIIIA alone is sufficient to prevent nucleosomal repression of a homologous 5S gene.

Plasmid DNA harbouring the human 5S rRNA gene was assembled into nucleosomes using either Xenopus S150 extracts or purified core histones in the presence of pectin. In both cases reconstitution of nucleosomes led to a complete repression of transcription. This repression could be efficiently counteracted by preincubating the template DNA with highly purified hTFIIIA which allowed the protein to bind to the ICR of the 5S gene. By using an efficient and well-defined in vitro reconstitution system based on isolated core histones in the presence of pectin, which is devoid of endogenous transcription factors, we demonstrate here for the first time that human TFIIIA alone is sufficient to prevent nucleosomal repression of h5S gene transcription and that additional pol III transcription factors are not required to achieve this effect. Additionally, we investigated the binding of hTFIIIA to a mononucleosome reconstituted on the human 5S gene. DNAse I footprinting experiments reveal that the entire ICR of the human 5S gene is covered by the nucleosome, thereby precluding the subsequent binding of human TFIIIA to the promoter of the 5S gene

Process development in a miniplant scale - A multilevel - multiscale PSE approach for developing an improved Oxidative Coupling of Methane process

The oxidative coupling of methane (OCM) is a promising alternative route to olefins that converts methane to higher hydrocarbons and open up a new feedstock for the oil based industry. However, due to yield limitations of available catalysts and high separation costs for conventional gas processing, the OCM process has not been applied yet in the industry. Starting with process simulation and sensitivity studies a flexible mini-plant was built in this research so as to demonstrate technical feasibility of an efficient OCM process, model validity and to study long term effects. By this means a concurrent engineering approach was applied for the whole process while investigating each unit parallel. Moreover, catalyst with several reactor concepts like the fluidized bed and membrane reactor were investigated by CFD simulation, process simulation and experiments, in order to study catalyst life time, operation conditions and technical feasibility. Thus, the reaction section was improved from 16% yield to 18%. Furthermore, the separation part of the OCM process was energetically improved by an integrated down streaming unit for the CO2. Thus, an energetic improvement of more than 40% in comparison to a benchmark absorption - desorption based CO2 separation process was achieved. In addition to this, novel absorbents were studied starting with molecular simulation up to process simulation and experimental validation for the CO2 separation. The results of the integrated process development and optimization process for the OCM will be presented and an overview of the multi scale and multilevel Process System Engineering (PSE) approach will be given for the case study

Gestational diabetes alters functions in offspring's umbilical cord cells with implications for cardiovascular health

10.1210/en.2016-1889Endocrinology15872102-2112ENDOAGUSTO (Growing up towards Healthy Outcomes

Vibration Mitigation and Monitoring: A Case Study of Construction in a Museum

<p>Vibration from demolition and construction activities poses a serious risk to museum objects. This case study presents preventive conservation and vibration monitoring strategies developed in response to a large-scale renovation project on the floor directly below the Egyptian Art galleries of the Metropolitan Museum of Art in order to safeguard this fragile, ancient art collection. The paper discusses the methods and procedures that were developed not only to protect the art but also to allow visitors continued access to as much of the collection as possible during the work period. In advance of the construction, pilot testing was performed to determine the levels of vibrations caused by different tools, as well as to gain a better understanding of vibration propagation within the museum and to specific objects through their mounts, pedestals, and display shelves. Vibration prone installations were modified with isolation and/or dampening approaches to mitigate vibration, or when possible, selected objects were deinstalled. A variety of mitigation solutions were shown to be effective through testing. During the demolition and construction phase, continuous wireless vibration monitoring was provided from within the galleries, and sometimes from sensors directly on objects or their shelves to provide near real-time alerts to museum staff and construction personnel. Alert levels were based on frequency independent velocity levels.</p

Molecular pathways reflecting poor intrauterine growth are found in Wharton's jelly-derived mesenchymal stem cells

10.1093/humrep/deu209Human Reproduction29102287 - 2301HUREEGUSTO (Growing up towards Healthy Outcomes

Alterations to DNA methylation and expression of CXCL14 are associated with suboptimal birth outcomes

10.1038/jhg.2014.63Journal of human genetics599504 - 511GUSTO (Growing up towards Healthy Outcomes

The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis

An association between impaired fetal growth and the postnatal development of obesity has been established. Here, by comparing adipocytes differentiated from mesenchymal stem cells (MSCs) taken from the umbilical cord and derived from normal and growth-restricted neonates, we identified the transcription factor SOX6 as highly expressed only in growth-restricted individuals. We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST. We further show that SOX6 interacts with β-catenin in adipocytes, suggesting an inhibition of WNT/β-catenin signaling, thereby promoting adipogenesis. The upstream regulatory region of the MEST gene in MSCs from growth-restricted subjects harbors hypomethylated CpGs next to SOX6 binding motifs, and we found that SOX6 binding is impaired by adjacent CpG methylation. In summary, we report that SOX6 is a novel regulator of adipogenesis synergizing with epigenetic mechanisms