Steroid hormone regulation of EMP2 expression and localization in the endometrium

<p>Abstract</p> <p>Background</p> <p>The tetraspan protein epithelial membrane protein-2 (EMP2), which mediates surface display of diverse proteins, is required for endometrial competence in blastocyst implantation, and is uniquely correlated with poor survival from endometrial adenocarcinoma tumors. Because EMP2 is differentially expressed in the various stages of the murine and human estrous cycle, we tested the hypothesis that the steroid hormones progesterone and estrogen influence EMP2 expression and localization.</p> <p>Methods</p> <p>Frozen human proliferative and secretory endometrium were collected and analyzed for EMP2 expression using SDS-PAGE/Western blot analysis. The response of EMP2 to progesterone and estradiol was determined using a combination of real-time PCR, SDS-PAGE/Western blot analysis, and confocal immunofluorescence in the human endometrial carcinoma cell line RL95-2. To confirm the in vitro results, ovariectomized mice were treated with progesterone or estradiol, and EMP2 expression was analyzed using immunohistochemistry.</p> <p>Results</p> <p>Within normal human endometrium, EMP2 expression is upregulated in the secretory phase relative to the proliferative phase. To understand the role of steroid hormones on EMP2 expression, we utilized RL95-2 cells, which express both estrogen and progesterone receptors. In RL95-2 cells, both estradiol and progesterone induced EMP2 mRNA expression, but only progesterone induced EMP2 protein expression. To compare steroid hormone regulation of EMP2 between humans and mice, we analyzed EMP2 expression in ovarectomized mice. Similar to results observed in humans, progesterone upregulated endometrial EMP2 expression and induced EMP2 translocation to the plasma membrane. Estradiol did not promote translocation to the cell surface, but moderately induced EMP2 expression in cytoplasmic compartments in vivo.</p> <p>Conclusion</p> <p>These findings suggest that targeting of EMP2 to specific locations under the influence of these steroid hormones may be important for integrating the molecular responses required for implantation competence.</p

Strong Temporal Variation Over One Saturnian Year: From Voyager to Cassini

Here we report the combined spacecraft observations of Saturn acquired over one Saturnian year (~29.5 Earth years), from the Voyager encounters (1980–81) to the new Cassini reconnaissance (2009–10). The combined observations reveal a strong temporal increase of tropic temperature (~10 Kelvins) around the tropopause of Saturn (i.e., 50 mbar), which is stronger than the seasonal variability (~a few Kelvins). We also provide the first estimate of the zonal winds at 750 mbar, which is close to the zonal winds at 2000 mbar. The quasi-consistency of zonal winds between these two levels provides observational support to a numerical suggestion inferring that the zonal winds at pressures greater than 500 mbar do not vary significantly with depth. Furthermore, the temporal variation of zonal winds decreases its magnitude with depth, implying that the relatively deep zonal winds are stable with time

Epithelial Membrane Protein-2 Promotes Endometrial Tumor Formation through Activation of FAK and Src

Endometrial cancer is the most common gynecologic malignancy diagnosed among women in developed countries. One recent biomarker strongly associated with disease progression and survival is epithelial membrane protein-2 (EMP2), a tetraspan protein known to associate with and modify surface expression of certain integrin isoforms. In this study, we show using a xenograft model system that EMP2 expression is necessary for efficient endometrial tumor formation, and we have started to characterize the mechanism by which EMP2 contributes to this malignant phenotype. In endometrial cancer cells, the focal adhesion kinase (FAK)/Src pathway appears to regulate migration as measured through wound healing assays. Manipulation of EMP2 levels in endometrial cancer cells regulates the phosphorylation of FAK and Src, and promotes their distribution into lipid raft domains. Notably, cells with low levels of EMP2 fail to migrate and poorly form tumors in vivo. These findings reveal the pivotal role of EMP2 in endometrial cancer carcinogenesis, and suggest that the association of elevated EMP2 levels with endometrial cancer prognosis may be causally linked to its effect on integrin-mediated signaling

A survey for variable young stars with small telescopes: II - mapping a protoplanetary disc with stable structures at 0.15 au

The HOYS citizen science project conducts long term, multifilter, high cadence monitoring of large YSO samples with a wide variety of professional and amateur telescopes. We present the analysis of the light curve of V1490 Cyg in the Pelican Nebula. We show that colour terms in the diverse photometric data can be calibrated out to achieve a median photometric accuracy of 0.02 mag in broadband filters, allowing detailed investigations into a variety of variability amplitudes over timescales from hours to several years. Using Gaia DR2 we estimate the distance to the Pelican Nebula to be 870 +70 −55 pc. V1490 Cyg is a quasi-periodic dipper with a period of 31.447 ± 0.011 d. The obscuring dust has homogeneous properties, and grains larger than those typical in the ISM. Larger variability on short timescales is observed in U and Rc−Hα, with U-amplitudes reaching 3 mag on timescales of hours, indicating the source is accreting. The Hα equivalent width and NIR/MIR colours place V1490 Cyg between CTTS/WTTS and transition disk objects. The material responsible for the dipping is located in a warped inner disk, about 0.15 AU from the star. This mass reservoir can be filled and emptied on time scales shorter than the period at a rate of up to 10−10 M�/yr, consistent with low levels of accretion in other T Tauri stars. Most likely the warp at this separation from the star is induced by a protoplanet in the inner accretion disk. However, we cannot fully rule out the possibility of an AA Tau-like warp, or occultations by the Hill sphere around a forming planet

The First Post-Kepler Brightness Dips of KIC 8462852

We present a photometric detection of the first brightness dips of the unique variable star KIC 8462852 since the end of the Kepler space mission in 2013 May. Our regular photometric surveillance started in October 2015, and a sequence of dipping began in 2017 May continuing on through the end of 2017, when the star was no longer visible from Earth. We distinguish four main 1-2.5% dips, named "Elsie," "Celeste," "Skara Brae," and "Angkor", which persist on timescales from several days to weeks. Our main results so far are: (i) there are no apparent changes of the stellar spectrum or polarization during the dips; (ii) the multiband photometry of the dips shows differential reddening favoring non-grey extinction. Therefore, our data are inconsistent with dip models that invoke optically thick material, but rather they are in-line with predictions for an occulter consisting primarily of ordinary dust, where much of the material must be optically thin with a size scale <<1um, and may also be consistent with models invoking variations intrinsic to the stellar photosphere. Notably, our data do not place constraints on the color of the longer-term "secular" dimming, which may be caused by independent processes, or probe different regimes of a single process

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

A survey for variable young stars with small telescopes: IX - Evolution of spot properties on YSOs in IC 5070

We present spot properties on 32 periodic young stellar objects in IC 5070. Long term, ∼5 yr, light curves in the V, R, and I-bands are obtained through the HOYS (Hunting Outbursting Young Stars) citizen science project. These are dissected into six months long slices, with 3 months oversampling, to measure 234 sets of amplitudes in all filters. We fit 180 of these with reliable spot solutions. Two thirds of spot solutions are cold spots, the lowest is 2150 K below the stellar temperature. One third are warm spots that are above the stellar temperature by less than ∼2000 K. Cold and warm spots have maximum surface coverage values of 40 per cent, although only 16 per cent of warm spots are above 20 per cent surface coverage as opposed to 60 per cent of the cold spots. Warm spots are most likely caused by a combination of plages and low density accretion columns, most common on objects without inner disc excess emission in K − W2. Five small hot spot solutions have &amp;lt;3 percent coverage and are 3000 – 5000 K above the stellar temperature. These are attributed to accretion, and four of them occur on the same object. The majority of our objects are likely to be accreting. However, we observe very few accretion hot spots as either the accretion is not stable on our timescale or the photometry is dominated by other features. We do not identify cyclical spot behaviour on the targets. We additionally identify and discuss a number of objects that have interesting amplitudes, phase changes, or spot properties

A survey for variable young stars with small telescopes – VIII. Properties of 1687 Gaia selected members in 21 nearby clusters

The Hunting Outbursting Young Stars (HOYS) project performs long-term, optical, multi-filter, high cadence monitoring of 25 nearby young clusters and star forming regions. Utilising Gaia DR3 data we have identified about 17000 potential young stellar members in 45 coherent astrometric groups in these fields. Twenty one of them are clear young groups or clusters of stars within one kiloparsec and they contain 9143 Gaia selected potential members. The cluster distances, proper motions and membership numbers are determined. We analyse long term (≈ 7 yr) V, R, and I-band light curves from HOYS for 1687 of the potential cluster members. One quarter of the stars are variable in all three optical filters, and two thirds of these have light curves that are symmetric around the mean. Light curves affected by obscuration from circumstellar materials are more common than those affected by accretion bursts, by a factor of 2 – 4. The variability fraction in the clusters ranges from 10 to almost 100 percent, and correlates positively with the fraction of stars with detectable inner disks, indicating that a lot of variability is driven by the disk. About one in six variables shows detectable periodicity, mostly caused by magnetic spots. Two thirds of the periodic variables with disk excess emission are slow rotators, and amongst the stars without disk excess two thirds are fast rotators – in agreement with rotation being slowed down by the presence of a disk

A survey for variable young stars with small telescopes: VIII — Properties of 1687 Gaia selected members in 21 nearby clusters

The Hunting Outbursting Young Stars (HOYS) project performs long-term, optical, multi- filter, high cadence monitoring of 25 nearby young clusters and star forming regions. Utilising Gaia DR3 data we have identified about 17000 potential young stellar members in 45 coherent astrometric groups in these fields. Twenty one of them are clear young groups or clusters of stars within one kiloparsec and they contain 9143 Gaia selected potential members. The cluster distances, proper motions and membership numbers are determined. We analyse long term ( 7 yr) V, R, and I-band light curves from HOYS for 1687 of the potential cluster members. One quarter of the stars are variable in all three optical filters, and two thirds of these have light curves that are symmetric around the mean. Light curves affected by obscuration from circumstellar materials are more common than those affected by accretion bursts, by a factor of 2 – 4. The variability fraction in the clusters ranges from 10 to almost 100 percent, and correlates positively with the fraction of stars with detectable inner disks, indicating that a lot of variability is driven by the disk. About one in six variables shows detectable periodicity, mostly caused by magnetic spots. Two thirds of the periodic variables with disk excess emission are slow rotators, and amongst the stars without disk excess two thirds are fast rotators – in agreement with rotation being slowed down by the presence of a disk