CCAAT/enhancer-binding proteins are key regulators of human type two deiodinase expression in a placenta cell line

An appropriate concentration of intracellular T(3) is a critical determinant of placenta development and function and is mainly controlled by the activity of type II deiodinase (D2). The levels of this enzyme are finely regulated in different tissues by coordinated transcriptional mechanisms, which rely on dedicated promoter sequences (e.g. cAMP response element and TATA elements) that impart inducibility and tissue specificity to Dio2 mRNA expression. Here we show that CCAAT enhancer-binding proteins α and β (C/EBPα and C/EBPβ) promote Dio2 expression in the trophoblastic cell line JEG3 through a conserved CCAAT element, which is a novel key component of the Dio2 promoter code that confers tissue-specific expression of D2 in these cells. Increased C/EBPs levels potently induce Dio2 transcription, whereas their ablation results in loss of Dio2 mRNA. By measuring the activity of several deletion and point mutant promoter constructs, we have identified the functional CCAAT element responsible for this effect, which is located in close proximity to the most 5' TATA box. Notably, this newly identified sequence is highly conserved throughout the species and binds in vivo and in vitro C/EBP, indicating the relevance of this regulatory mechanism. Together, our results unveil a novel mechanism of regulation of D2 expression in a trophoblastic cell line, which may play a relevant role during placenta development

Resistive damping implementation as a method to improve controllability in stiff ohmic RF-MEMS switches

This paper presents in detail the entire procedure of calculating the bias resistance of an ohmic RF-MEMS switch, controlled under resistive damping (charge drive technique). In case of a very stiff device, like the North Eastern University switch, the actuation control under resistive damping is the only way to achieve controllability. Due to the short switching time as well as the high actuation voltage, it is not practical to apply a tailored control pulse (voltage drive control technique). Implementing a bias resistor of 33 MΩ in series with the voltage source, the impact velocity of the cantilever has been reduced 80 % (13.2 from 65.9 cm/s), eliminating bouncing and high initial impact force during the pull-down phase. However, this results in an affordable cost of switching time increase from 2.38 to 4.34 μs. During the release phase the amplitude of bouncing has also been reduced 34 % (174 from 255 nm), providing significant improvement in both switching operation phases of the switch. © 2013 Springer-Verlag Berlin Heidelberg

Human Indoor Exposure to Airborne Halogenated Flame Retardants: Influence of Airborne Particle Size

Inhalation of halogenated flame-retardants (HFRs) released from consumer products is an important route of exposure. However, not all airborne HFRs are respirable, and thus interact with vascular membranes within the gas exchange (alveolar) region of the lung. HFRs associated with large (\u3e 4 mu m), inhalable airborne particulates are trapped on the mucosal lining of the respiratory tract and then are expelled or swallowed. The latter may contribute to internal exposure via desorption from particles in the digestive tract. Exposures may also be underestimated if personal activities that re-suspend particles into the breathing zone are not taken into account. Here, samples were collected using personal air samplers, clipped to the participants\u27 shirt collars (n = 18). We observed that the larger, inhalable air particulates carried the bulk (\u3e92%) of HFRs. HFRs detected included those removed from commerce (i.e., polybrominated diphenyl ethers (Penta-BDEs: BDE-47, -85, -100, -99, and -153)), their replacements; e.g., 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB or EH-TBB); bis(2-ethylhexyl) 3,4,5,6-tetrabromophthalate (TBPH or BEH-TEBP) and long-produced chlorinated organophosphate-FRs (ClOPFRs): tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCPP or TCIPP), and tris(1,3-dichloro-2-propyl) phosphate (TDCPP or TDCIPP). Our findings suggest estimates relying on a single exposure route, i.e., alveolar gas exchange, may not accurately estimate HFR internal dosage, as they ignore contributions from larger inhalable particulates that enter the digestive tract. Consideration of the fate and bioavailability of these larger particulates resulted in higher dosage estimates for HFRs with log K-oa \u3c 12 (i.e., Penta-BDEs and ClOPFRs) and lower estimates for those with log Koa \u3e 12 (i.e., TBB and TBPH) compared to the alveolar route exposure alone. Of those HFRs examined, the most significant effect was the lower estimate by 41% for TBPH. The bulk of TBPH uptake from inhaled particles was estimated to be through the digestive tract, with lower bioavailability. We compared inhalation exposure estimates to chronic oral reference doses (RfDs) established by several regulatory agencies. The U.S. Environmental Protection Agency (EPA) RfD levels for several HFRs are considered outdated; however, BDE-99 levels exceeded those suggested by the Dutch National Institute for Public Health and the Environment (RIVM) by up to 26 times. These findings indicate that contributions and bioavailability of respirable and inhalable airborne particulates should both be considered in future risk assessments

Plasma membrane redox system in the erythrocytes of rowers: Pilot study

The oxidative stress results from a change in the physiological balance between oxidant and antioxidant species. This type of stress is a chemical change in the redox state of cells. The increased production of reactive species is related to an excessive metabolic activation, for example, from an intense physical exercise or an excessive caloric intake (1). In physiological conditions, muscle fibers are provided with an antioxidant system able to keep under control the excessive production of Reactive Oxygen Species (ROS)

Vitamin D in cancer chemoprevention

Context: There is increasing evidence that Vitamin D (Vit D) and its metabolites, besides their well-known calcium-related functions, may also exert antiproliferative, pro-differentiating, and immune modulatory effects on tumor cells in vitro and may also delay tumor growth in vivo. Objective: The aim of this review is to provide fresh insight into the most recent advances on the role of Vit D and its analogues as chemopreventive drugs in cancer therapy. Methods: A systematic review of experimental and clinical studies on Vit D and cancer was undertaken by using the major electronic health database including ISI Web of Science, Medline, PubMed, Scopus and Google Scholar. Results and conclusion: Experimental and clinical observations suggest that Vit D and its analogues may be effective in preventing the malignant transformation and/or the progression of various types of human tumors including breast cancer, prostate cancer, colorectal cancer, and some hematological malignances. These findings suggest the possibility of the clinical use of these molecules as novel potential chemopreventive and anticancer agent

Computing Linear Matrix Representations of Helton-Vinnikov Curves

Helton and Vinnikov showed that every rigidly convex curve in the real plane bounds a spectrahedron. This leads to the computational problem of explicitly producing a symmetric (positive definite) linear determinantal representation for a given curve. We study three approaches to this problem: an algebraic approach via solving polynomial equations, a geometric approach via contact curves, and an analytic approach via theta functions. These are explained, compared, and tested experimentally for low degree instances.Comment: 19 pages, 3 figures, minor revisions; Mathematical Methods in Systems, Optimization and Control, Birkhauser, Base

“Leptin and leptin receptor expression in asthma”

Background: The adipokine leptin is a potential new mediator for bronchial epithelial homeostasis. Asthma is a chronic inflammatory disease characterized by airway remodeling that might affect disease chronicity and severity. TGF-b is a tissue growth factor the dysregulation of which is associated with airway remodeling. Objective: We sought to determine whether a bronchial epithelial dysfunction of the leptin/leptin receptor pathway contributes to asthma pathogenesis and severity. Methods: We investigated in vitro the presence of leptin/leptin receptor on human bronchial epithelial cells. Then we studied the effect of TGF-b and fluticasone propionate on leptin receptor expression. Finally, the role of leptin on TGF-b release and cell proliferation was analyzed. Ex vivo we investigated the presence of leptin/leptin receptor in the epithelium of bronchial biopsy specimens from subjects with asthma of various severities and from healthy volunteers, and some features of airway remodeling, such as reticular basement membrane (RBM) thickness and TGF-b expression in the epithelium, were assessed. Results: In vitro bronchial epithelial cells express leptin/leptin receptor. TGF-b decreased and fluticasone propionate increased leptin receptor expression, and leptin decreased the spontaneous release of TGF-b and increased cell proliferation. Ex vivo the bronchial epithelium of subjects with mild, uncontrolled, untreated asthma showed a decrease expression of leptin and its receptor and an increased RBM thickness and TGF-b expression when compared with values seen in healthy volunteers. Furthermore, severe asthma was associated with a reduced expression of leptin and its receptor and an increased RBM thickness with unaltered TGF-b expression. Conclusions: Decreased expression of leptin/leptin receptor characterizes severe asthma and is associated with airway remodeling features