Unregulated miR-96 Induces Cell Proliferation in Human Breast Cancer by Downregulating Transcriptional Factor FOXO3a

FOXO transcription factors are key tumor suppressors in mammalian cells. Until now, suppression of FOXOs in cancer cells was thought to be mainly due to activation of multiple onco-kinases by a phosphorylation-ubiquitylation-mediated cascade. Therefore, it was speculated that inhibition of FOXO proteins would naturally occur through a multiple step post-translational process. However, whether cancer cells may downregulate FOXO protein via an alternative regulatory mechanism is unclear. In the current study, we report that expression of miR-96 was markedly upregulated in breast cancer cells and breast cancer tissues compared with normal breast epithelial cells (NBEC) and normal breast tissues. Ectopic expression of miR-96 induced the proliferation and anchorage-independent growth of breast cancer cells, while inhibition of miR-96 reduced this effect. Furthermore, upregulation of miR-96 in breast cancer cells resulted in modulation of their entry into the G1/S transitional phase, which was caused by downregulation of cyclin-dependent kinase (CDK) inhibitors, p27Kip1 and p21Cip1, and upregulation of the cell-cycle regulator cyclin D1. Moreover, we demonstrated that miR-96 downregulated FOXO3a expression by directly targeting the FOXO3a 3′-untranslated region. Taken together, our results suggest that miR-96 may play an important role in promoting proliferation of human breast cancer cells and present a novel mechanism of miRNA-mediated direct suppression of FOXO3a expression in cancer cells

Legacy mercury releases during copper mining near Lake Superior

© 2015 International Association for Great Lakes Research. To examine issues of mercury contamination in lake sediments and fish, we require insight into historic sources of mercury and details of watershed methyl mercury (MeHg) cycling. Modern-day National Atmospheric Deposition Program (NADP) estimates of atmospheric mercury deposition in the upper Midwest region range from 4-10 μg/m2/y (wet only) to 5-30 μg/m2/y (gross deposition). Sedimentary records from scattered Michigan lakes, removed from mining sites, record around 5-24 μg/m2/y modern THg deposition. However, these values are not representative of historic deposition near mining sites. On the Keweenaw Peninsula, mercury occurs naturally in copper ores and was discharged by smelting and stamp mill (tailings) operations. Here we examine mercury fluxes into two lakes (Portage and Torch Lake, portions of the Keweenaw Waterway) off Lake Superior, part of the previous Torch Lake Superfund site. Total mercury fluxes document greatly enhanced mercury loading (mean ca. 1590 μg/m2/y; peaks of 5120 to 21,300 μg/m2/y) during the height of copper mining (1880-1930), followed by a rapid decline once activities ceased. Methylmercury profiles appear to document both current methylation and historic methylation during mining operations. Time differences in MeHg and THg profiles may relate to watershed delivery time lags, toxic effects of copper on methylating bacteria, or to stratigraphic mobility. Whereas rapid sedimentation and lowered copper flux are promoting ecosystem recovery in Portage Lake, slower burial by organic-rich sediments is enhancing metal concentrations in Torch Lake sediments

Mining legacy across a wetland landscape: High mercury in Upper Peninsula (Michigan) rivers, lakes, and fish

© The Royal Society of Chemistry 2018. A geographic enigma is that present-day atmospheric deposition of mercury in the Upper Peninsula of Michigan is low (48%) and that regional industrial emissions have declined substantially (ca. 81% reduction) relative to downstate. Mercury levels should be declining. However, state (MDEQ) surveys of rivers and lakes revealed elevated total mercury (THg) in Upper Peninsula waters and sediment relative to downstate. Moreover, Western Upper Peninsula (WUP) fish possess higher methyl mercury (MeHg) levels than Northern Lower Peninsula (NLP) fish. A contributing explanation for elevated THg loading is that a century ago the Upper Peninsula was a major industrial region, centered on mining. Many regional ores (silver, copper, zinc, massive sulfides) contain mercury in part per million concentrations. Copper smelters and iron furnace-taconite operations broadcast mercury almost continuously for 140 years, whereas mills discharged tailings and old mine shafts leaked contaminated water. We show that mercury emissions from copper and iron operations were substantial (60-650 kg per year) and dispersed over relatively large areas. Moreover, lake sediments in the vicinity of mining operations have higher THg concentrations. Sediment profiles from the Keweenaw Waterway show that THg accumulation increased 50- to 400-fold above modern-day atmospheric deposition levels during active mining and smelting operations, with lingering MeHg effects. High MeHg concentrations are geographically correlated with low pH and dissolved organic carbon (DOC), a consequence of biogeochemical cycling in wetlands, characteristic of the Upper Peninsula. DOC can mobilize metals and elevate MeHg concentrations. We argue that mercury loading from mining is historically superimposed upon strong regional wetland effects, producing a combined elevation of both THg and MeHg in the Western Upper Peninsula

Impact of the transponder configuration on the Asia-Europe TWSTFT network

International audienceTwo-way satellite time and frequency transfer between Asia and Europe has been performed for many years first by a two-transponder and later by a one-transponder configuration on the IS-4 and the AM-2 satellites, respectively. A diurnal phase instability was observed in links established through IS-4, while such instability has not been observed when AM-2 was used. It could be shown that the diurnal variation are site-independent. An on-board path asymmetry due to the use of two transponders seems thus to cause it

ITO Interface Modifiers Can Improve <i>V</i>_OC in Polymer Solar Cells and Suppress Surface Recombination

We use dipolar phosphonic acid self-assembled monolayers (PA SAMs) to modify the work function of the hole-extracting contact in polymer/fullerene bulk heterojunction solar cells. We observe a linear dependence of the open-circuit voltage (<i>V</i>_OC) of these organic photovoltaic devices on the modified indium tin oxide (ITO) work function when using a donor polymer with a deep-lying ionization energy. With specific SAMs, we can obtain <i>V</i>_OC values exceeding those obtained with the common poly­(3,4-ethylenedioxythiophene)-poly­(styrenesulfonate) (PEDOT:PSS) hole-extraction layer. We measure charge-carrier lifetimes and densities using transient photovoltage and charge extraction in a series of devices with SAM-modified contacts. As expected, these measurements show systematically longer carrier lifetimes in devices with higher <i>V</i>_OC values; however, the trends provide useful distinctions between different hypotheses of how transient photovoltage decays might be controlled by surface chemistry. We interpret our results as being consistent with changes in the band bending at the ITO/bulk heterojunction interface that have the net result of altering the internal electric field to help prevent electrons in fullerene domains from undergoing surface recombination at the hole-extracting electrode