Estrogen down-regulates uncoupling proteins and increases oxidative stress in breast cancer

Oxidative stress has been postulated as one of the mechanisms underlying the estrogen carcinogenic effect in breast cancer. Estrogens are known to increase mitochondrial-derived reactive oxygen species (ROS) by an unknown mechanism. Given that uncoupling proteins (UCPs) are key regulators of mitochondrial energy efficiency and ROS production, our aim was to check the presence and activity of UCPs in estrogen receptor (ER)-positive and ER-negative breast cancer cells and tumors, as well as their relation to oxidative stress. Estrogen (1 nM) induced higher oxidative stress in the ER-positive MCF-7 cell line, showing increased mitochondrial membrane potential, H₂O₂ levels, and DNA and protein damage compared to ER-negative MDA-MB-231 cells. All isoforms of uncoupling proteins were highly expressed in ER-positive breast cancer cells and tumors compared to negative ones. ROS production in mitochondria isolated from MCF-7 was increased by inhibition of UCPs with GDP, but not in mitochondria from MDA-MB-231. Estrogen treatment decreased uncoupling protein and catalase levels in MCF-7 and decreased GDP-dependent ROS production in isolated mitochondria. On the whole, these results suggest that estrogens, through an ER-dependent mechanism, may increase mitochondrial ROS production by repressing uncoupling proteins, which offers a new perspective on the understanding of why estrogens are a risk factor for breast cancer.     

PHENOTYPIC DIFFERENTIATION AT SOUTHERN LIMIT BORDERS: THE CASE STUDY OF TWO FUCOID MACROALGAL SPECIES WITH DIFFERENT LIFE‐HISTORY TRAITS1

Marginal populations are often geographically isolated, smaller, and more fragmented than central populations and may frequently have to face suboptimal local environmental conditions. Persistence of these populations frequently involves the development of adaptive traits at phenotypic and genetic levels. We compared population structure and demographic variables in two fucoid macroalgal species contrasting in patterns of genetic diversity and phenotypic plasticity at their southern distribution limit with a more central location. Models were Ascophyllum nodosum (L.) Le Jol. (whose extreme longevity and generation overlap may buffer genetic loss by drift) and Fucus serratus L. (with low genetic diversity at southern margins). At edge locations, both species exhibited trends in life‐history traits compatible with population persistence but by using different mechanisms. Marginal populations of A. nodosum had higher reproductive output in spite of similar mortality rates at all life stages, making edge populations denser and with smaller individuals. In F. serratus, rather than demographic changes, marginal populations differed in habitat, occurring restricted to a narrower vertical habitat range. We conclude that persistence of both A. nodosum and F. serratus at the southern‐edge locations depends on different strategies. Marginal population persistence in A. nodosum relies on a differentiation in life‐history traits, whereas F. serratus, putatively poorer in evolvability potential, is restricted to a narrower vertical range at border locations. These results contribute to the general understanding of mechanisms that lead to population persistence at distributional limits and to predict population resilience under a scenario of environmental change.     

Guanidinium and aminoimidazolinium derivatives of N-(4-piperidyl)propanamides as potential ligands for mu opioid and I2-imidazoline receptors: synthesis and pharmacological screening

Derivatives of N-(1-phenethyl-4-piperidyl)propanamides incorporating guanidinium and 2-aminoimidazolinium groups have been prepared by a synthetic approach involving first introduction of a spacer between the piperidine and the functional group by reductive amination of piperidinone. The formation of each of these functional groups was carried out using N-N'-di(tert-butoxycarbonyl)thiourea and 2-methylthioimidazolinium iodide, respectively. These structures have been designed to incorporate two pharmacologic goals into one entity. Radioligand binding assays have been used to study their affinity for opioid (mu, delta and kappa) and I2-imidazoline receptors. Two of them, 10 and 16, showed high affinity for mu opioid receptors and functionally they had moderate analgesic properties in the hot plate and writhing tests. The in vitro studies on guinea pig ileum (GPI) indicated that both compounds are mu opioid agonists. In what concerns I2-imidazoline receptor activity, these derivatives showed low affinity around 6 to 7 times less than idazoxan.     

Advanced microbial analysis for wastewater quality monitoring: metagenomics trend

Applied Microbiology and Biotechnology - Urban Wastewater treatment plants (UWWTPs) have played an important and fundamental role in society for water purification of contaminated human wastewaters...     

Spectral attenuation of brain and retina tissues in the near‐infrared range measured using a fiber‐based supercontinuum device

A novel setup for the efficient constant optical measurements of biological tissues in the near infrared is presented. The system combines the use of a fiber‐based supercontinuum source with a simple optics fiber collimator. This configuration allows a wide spectral range of measurement and, at the same time, can efficiently filter the straightforward transmitted light while avoiding scattered light. As a performance example, the optical characterization of rat brain and retina tissues are shown. The attenuation coefficient for both tissues in the near infrared region is also obtained. This technique could be applied in clinical research as a noninvasive method with several potential practical applications.