17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor–positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2. Additionally, miR-149-5p downregulation promotes hnRNPA1 expression, responsible for the loading of let-7’s miRNAs into EVs. In multiple patient cohorts, we observed increased levels of let-7a-5p and let-7d-5p in EVs derived from the blood of premenopausal ER+ BC patients, and elevated EV levels in patients with high BMI, both conditions associated with higher levels of 17β-estradiol. In brief, we identified a unique estrogen-driven mechanism by which ER+ BC cells eliminate tumor suppressor miRNAs in EVs, with effects on modulating tumor-associated macrophages in the microenvironment

Demonstration of cooling by the Muon Ionization Cooling Experiment

The use of accelerated beams of electrons, protons or ions has furthered the development of nearly every scientific discipline. However, high-energy muon beams of equivalent quality have not yet been delivered. Muon beams can be created through the decay of pions produced by the interaction of a proton beam with a target. Such ‘tertiary’ beams have much lower brightness than those created by accelerating electrons, protons or ions. High-brightness muon beams comparable to those produced by state-of-the-art electron, proton and ion accelerators could facilitate the study of lepton–antilepton collisions at extremely high energies and provide well characterized neutrino beams1,2,3,4,5,6. Such muon beams could be realized using ionization cooling, which has been proposed to increase muon-beam brightness7,8. Here we report the realization of ionization cooling, which was confirmed by the observation of an increased number of low-amplitude muons after passage of the muon beam through an absorber, as well as an increase in the corresponding phase-space density. The simulated performance of the ionization cooling system is consistent with the measured data, validating designs of the ionization cooling channel in which the cooling process is repeated to produce a substantial cooling effect9,10,11. The results presented here are an important step towards achieving the muon-beam quality required to search for phenomena at energy scales beyond the reach of the Large Hadron Collider at a facility of equivalent or reduced footprint6

Transverse Emittance Reduction in Muon Beams by Ionization Cooling

Accelerated muon beams have been considered for next-generation studies of high-energy lepton-antilepton collisions and neutrino oscillations. However, high-brightness muon beams have not yet been produced. The main challenge for muon acceleration and storage stems from the large phase-space volume occupied by the beam, derived from the muon production mechanism through the decay of pions from proton collisions. Ionization cooling is the technique proposed to decrease the muon beam phase-space volume. Here we demonstrate a clear signal of ionization cooling through the observation of transverse emittance reduction in beams that traverse lithium hydride or liquid hydrogen absorbers in the Muon Ionization Cooling Experiment (MICE). The measurement is well reproduced by the simulation of the experiment and the theoretical model. The results shown here represent a substantial advance towards the realization of muon-based facilities that could operate at the energy and intensity frontiers.Comment: 23 pages and 5 figure

First demonstration of ionization cooling by the Muon Ionization Cooling Experiment

High-brightness muon beams of energy comparable to those produced by state-of-the-art electron, proton and ion accelerators have yet to be realised. Such beams have the potential to carry the search for new phenomena in lepton-antilepton collisions to extremely high energy and also to provide uniquely well-characterised neutrino beams. A muon beam may be created through the decay of pions produced in the interaction of a proton beam with a target. To produce a high-brightness beam from such a source requires that the phase space volume occupied by the muons be reduced (cooled). Ionization cooling is the novel technique by which it is proposed to cool the beam. The Muon Ionization Cooling Experiment collaboration has constructed a section of an ionization cooling cell and used it to provide the first demonstration of ionization cooling. We present these ground-breaking measurements.Comment: 19 pages and 6 figure

Time trends in leisure time physical activity and physical fitness in elderly people: 20 year follow-up of the Spanish population national health survey (1987-2006)

<p>Abstract</p> <p>Background</p> <p>To estimate trends in leisure time physical activity and physical fitness between 1987-2006 in older Spanish people.</p> <p>Methods</p> <p>We analyzed data collected from the Spanish National Health Surveys conducted in 1987 (n = 29,647), 1993 (n = 20,707), 1995-1997 (n = 12,800), 2001 (n = 21,058), 2003 (n = 21,650), and 2006 (n = 29,478). The number of subjects aged ≥ 65 years included in the current study was 29,263 (1987: n = 4,958-16.7%; 1993: n = 3,751-17.8%; 1995-97: n = 2,229-17.4%; 2001: n = 4,356-20.7%; 2003: 6,134-28.3%; 2006: 7,835-26.5%). Main variables included leisure-time physical activity and physical fitness. We analyzed socio-demographic characteristics, self-rated health status, lifestyle habit and co-morbid conditions using multivariate logistic regression models.</p> <p>Results</p> <p>Women exhibited lower prevalence of leisure time physical activity and physical fitness compared to men (P < 0.05). The multivariate analysis for time trends found that practising leisure time physical activity increased from 1987 to 2006 (P < 0.001). Variables associated with a lower likelihood of practicing leisure time physical activity were: age ≥ 80 years old, ≥ 2 co-morbid chronic conditions, and obesity. Variables associated with lower physical fitness included: age ≥ 80 years, worse self rated health; ≥ 2 medications (only for walking), and obesity.</p> <p>Conclusions</p> <p>We found an increase in leisure time physical activity in the older Spanish population. Older age, married status, co-morbid conditions, obesity, and worse self-perceived health status were associated with lower activity. Identification of these factors can help to identify individuals at risk for physical inactivity.</p

First demonstration of ionization cooling by the muon ionization cooling experiment

High-brightness muon beams of energy comparable to those produced by state-of-the-art electron, proton and ion accelerators have yet to be realised. Such beams have the potential to carry the search for new phenomena in lepton-antilepton collisions to extremely high energy and also to provide uniquely well-characterised neutrino beams. A muon beam may be created through the decay of pions produced in the interaction of a proton beam with a target. To produce a high-brightness beam from such a source requires that the phase space volume occupied by the muons be reduced (cooled). Ionization cooling is the novel technique by which it is proposed to cool the beam. The Muon Ionization Cooling Experiment collaboration has constructed a section of an ionization cooling cell and used it to provide the first demonstration of ionization cooling. We present these ground-breaking measurements

Physical activity and risk of Metabolic Syndrome in an urban Mexican cohort

Abstract Background In the Mexican population metabolic syndrome (MS) is highly prevalent. It is well documented that regular physical activity (PA) prevents coronary diseases, type 2 diabetes and MS. Most studies of PA have focused on moderate-vigorous leisure-time activity, because it involves higher energy expenditures, increase physical fitness, and decrease the risk of MS. However, for most people it is difficult to get a significant amount of PA from only moderately-vigorous leisure activity, so workplace activity may be an option for working populations, because, although may not be as vigorous in terms of cardio-respiratory efforts, it comprises a considerable proportion of the total daily activity with important energy expenditure. Since studies have also documented that different types and intensity of daily PA, including low-intensity, seem to confer important health benefits such as prevent MS, we sought to assess the impact of different amounts of leisure-time and workplace activities, including low-intensity level on MS prevention, in a sample of urban Mexican adults. Methods The study population consisted of 5118 employees and their relatives, aged 20 to 70 years, who were enrolled in the baseline evaluation of a cohort study. MS was assessed according to the criteria of the National Cholesterol Education Program, ATP III and physical activity with a validated self-administered questionnaire. Associations between physical activity and MS risk were assessed with multivariate logistic regression models. Results The prevalence of the components of MS in the study population were: high glucose levels 14.2%, high triglycerides 40.9%, high blood pressure 20.4%, greater than healthful waist circumference 43.2% and low-high density lipoprotein 76.9%. The prevalence of MS was 24.4%; 25.3% in men and 21.8% in women. MS risk was reduced among men (OR 0.72; 95%CI 0.57–0.95) and women (OR 0.78; 95%CI 0.64–0.94) who reported an amount of ≥30 minutes/day of leisure-time activity, and among women who reported an amount of ≥3 hours/day of workplace activity (OR 0.75; 95%CI 0.59–0.96). Conclusion Our results indicate that both leisure-time and workplace activity at different intensity levels, including low-intensity significantly reduce the risk of MS. This finding highlights the need for more recommendations regarding the specific amount and intensity of leisure-time and workplace activity needed to prevent MS

Measurements of the νμ\nu_{\mu} and νˉμ\bar{\nu}_{\mu}-induced Coherent Charged Pion Production Cross Sections on 12C^{12}C by the T2K experiment

We report an updated measurement of the $\nu_{\mu}$-induced, and the first measurement of the $\bar{\nu}_{\mu}$-induced coherent charged pion production cross section on $^{12}C$ nuclei in the T2K experiment. This is measured in a restricted region of the final-state phase space for which $p_{\mu,\pi} > 0.2$ GeV, $\cos(\theta_{\mu}) > 0.8$ and $\cos(\theta_{\pi}) > 0.6$, and at a mean (anti)neutrino energy of 0.85 GeV using the T2K near detector. The measured $\nu_{\mu}$ CC coherent pion production flux-averaged cross section on $^{12}C$ is $(2.98 \pm 0.37 (stat.) \pm 0.31 (syst.) \substack{ +0.49 \\ -0.00 } \mathrm{ (Q^2\,model)}) \times 10^{-40}~\mathrm{cm}^{2}$. The new measurement of the $\bar{\nu}_{\mu}$-induced cross section on $^{12}{C}$ is $(3.05 \pm 0.71 (stat.) \pm 0.39 (syst.) \substack{ +0.74 \\ -0.00 } \mathrm{(Q^2\,model)}) \times 10^{-40}~\mathrm{cm}^{2}$. The results are compatible with both the NEUT 5.4.0 Berger-Sehgal (2009) and GENIE 2.8.0 Rein-Sehgal (2007) model predictions