Proteomics demonstration that normal breast epithelial cells can induce apoptosis of breast cancer cells through insulin-like growth factor-binding protein-3 and maspin

Normal breast epithelial cells are known to exert an apoptotic effect on breast cancer cells, resulting in a potential paracrine inhibition of breast tumor development. In this study we purified and characterized the apoptosis-inducing factors secreted by normal breast epithelial cells. Conditioned medium was concentrated by ultrafiltration and separated on reverse phase Sep-Pak C18 and HPLC. The proapoptotic activity of eluted fractions was tested on MCF-7 breast cancer cells, and nano-LC-nano-ESI-MS/MS allowed the identification of insulin-like growth factor-binding protein-3 (IGFBP-3) and maspin as the proapoptotic factors produced by normal breast epithelial cells. Western blot analysis of conditioned media confirmed the specific secretion of IGFBP-3 and maspin by normal cells but not by breast cancer cells. Immunodepletion of IGFBP-3 and maspin completely abolished the normal cell-induced apoptosis of cancer cells, and recombinant proteins reproduced the effect of normal cell-conditioned medium on apoptosis of breast cancer cells. Together our results indicated that normal breast epithelial cells can induce apoptosis of breast cancer cells through IGFBP-3 and maspin. These findings provide a molecular hypothesis for the long observed inhibitory effect of normal surrounding cells on breast cancer development.     

A novel in vitro propagation system for West Indian elm [Guazuma ulmifolia Lam. (Malvaceae)]: a valuable medicinal woody species

In Vitro Cellular & Developmental Biology - Plant - The aim of this study was to establish a system of in vitro germination and propagation of Guazuma ulmifolia Lam. microcuttings (Malvaceae)....     

Prolonged elevated levels of c-kit+ progenitor cells after a myocardial infarction by beta 2 adrenergic receptor priming

Endogenous progenitor cells may participate in cardiac repair after a myocardial infarction (MI). The beta 2 adrenergic receptor (ß2-AR) pathway induces proliferation of c-kit+ cardiac progenitor cells (CPC) in vitro. We investigated if ß2-AR pharmacological stimulation could ameliorate endogenous CPC-mediated regeneration after a MI. C-kit+ CPC ß1-AR and ß2-AR expression was evaluated in vivo and in vitro. A significant increase in the percentage of CPCs expressing ß1-AR and ß2-AR was measured 7 days post-MI. Accordingly, 24 hrs of low serum and hypoxia in vitro significantly increased CPC ß2-AR expression. Cell viability and differentiation assays validated a functional role of CPC ß2-AR. The effect of pharmacological activation of ß2-AR was studied in C57 mice using fenoterol administered in the drinking water 1 week before MI or sham surgery or at the time of the surgery. MI induced a significant increase in the percentage of c-kit+ progenitor cells at 7 days, whereas pretreatment with fenoterol prolonged this response resulting in a significant elevated number of CPC up to 21 days post-MI. This increased number of CPC correlated with a decrease in infarct size. The immunofluorescence analysis of the heart tissue for proliferation, apoptosis, macrophage infiltration, cardiomyocytes surface area, and vessel density showed significant changes on the basis of surgery but no benefit due to fenoterol treatment. Cardiac function was not ameliorated by fenoterol administration when evaluated by echocardiography. Our results suggest that ß2-AR stimulation may improve the cardiac repair process by supporting an endogenous progenitor cell response but is not sufficient to improve the cardiac function.     

Functional integration for enrolment constrains evolutionary variation of phacopid trilobites despite developmental modularity

Modularity and integration are variational properties expressed at various levels of the biological hierarchy. Mismatches among these levels, for example developmental modules that are integrated in a functional unit, could be informative of how evolutionary processes and trade‐offs have shaped organismal morphologies as well as clade diversification. In the present study, we explored the full, integrated and modular spaces of two developmental modules in phacopid trilobites, the cephalon and the pygidium, and highlight some differences among them. Such contrasts reveal firstly that evolutionary processes operating in the modular spaces are stronger in the cephalon, probably due to a complex regime of selection related to the numerous functions ensured by this module. Secondly, we demonstrate that the same pattern of covariation is shared among species, which also differentiate along this common functional integration. This common pattern might be the result of stabilizing selection acting on the enrolment and implying a coordinate variation between the cephalon and the pygidium in a certain direction of the morphospace. Finally, we noticed that Austerops legrandi differs slightly from other species in that its integration is partly restructured in the way the two modules interact. Such a divergence can result from the involvement of the cephalon in several vital functions that may have constrained the response of the features involved in enrolment and reorganized the covariation of the pygidium with the cephalon. Therefore, it is possible that important evolutionary trade‐offs between enrolment and other functions on the cephalon might have partly shaped the diversification of trilobites.     

The population dynamics of three polyphagous owlet moths (Lepidoptera: Noctuidae) and the influence of meteorological factors and ENSO on them

The owlet moths (Lepidoptera: Noctuidae) Anicla infecta (Ochsenheimer 1816), Elaphria agrotina (Guenée 1852) and Spodoptera frugiperda (J.E. Smith 1797) occur in the entire American continent. These polyphagous moths have a preference for grasses, and have different biological habits. In this study, the populations of these three species were evaluated monthly with light traps in the Brazilian Savannah, ranging a span of four crop seasons (from July, 2013 to June, 2017). The population data were analyzed and correlated with the meteorological variables: maximum temperature, minimum temperature, relative humidity and precipitation. A total of 4719 individuals were collected in the following percentages: A. infecta (n = 459; 9.73%), E. agrotina (n = 1809; 38.33%) and S. frugiperda (n = 2451; (51.94%). The abundance of all species went down from the first crop season (2013/2014) to the third (2015/2016). In the fourth crop season (2016/2017), the populations of A. infecta and E. agrotina stabilized, but the abundance of S. frugiperda experienced further decrease. The numbers of individuals of three species declined when precipitation was much above (crop season 2014/2015) and below (crop season 2015/2016) than expected by the climatological normal. There were significant, but different degrees of correlation, between the meteorological factors and the ONI index (Oceanic Niño Index - indicator for monitoring El Niño-Southern Oscillation or “ENSO”) with respect to monthly population variations. The results are discussed in accordance with principles of the Integrated Pest Management (IPM) in mind, given the continental distribution and agricultural importance of the three owlet moth species studied.     

Evolutionary fate of an unstable human minisatellite deduced from sperm-mutation spectra of individual alleles

Although mutation processes at some human minisatellites have been extensively characterized, the evolutionary fate of these unstable loci is unknown. Minisatellite instability is largely germline specific, with mutation rates up to several percent and with expansion events predominating over contractions. Using allele-specific small-pool polymerase chain reaction, we have determined sperm-mutation spectra of individual alleles of the highly unstable human minisatellite CEB1 (i.e., D2S90). We show that, as allele size increases, the proportion of contractions rises from <5% to 50%, with the average size of deletion increasing and eventually exceeding the average size of expansion. The expected net effect of these trends after many generations is an equilibrium distribution of allele sizes, and allele-frequency data suggest that this equilibrium state has been reached in some contemporary human populations.