The fidelity of intracellular signaling hinges on the organization of dynamic activity architectures. Spatial compartmentation was first proposed over 30 years ago to explain how diverse G ...protein-coupled receptors achieve specificity despite converging on a ubiquitous messenger, cyclic adenosine monophosphate (cAMP). However, the mechanisms responsible for spatially constraining this diffusible messenger remain elusive. Here, we reveal that the type I regulatory subunit of cAMP-dependent protein kinase (PKA), RIα, undergoes liquid-liquid phase separation (LLPS) as a function of cAMP signaling to form biomolecular condensates enriched in cAMP and PKA activity, critical for effective cAMP compartmentation. We further show that a PKA fusion oncoprotein associated with an atypical liver cancer potently blocks RIα LLPS and induces aberrant cAMP signaling. Loss of RIα LLPS in normal cells increases cell proliferation and induces cell transformation. Our work reveals LLPS as a principal organizer of signaling compartments and highlights the pathological consequences of dysregulating this activity architecture.
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•PKA RIα undergoes liquid-liquid phase separation in response to cAMP dynamics•RIα condensates dynamically sequester cAMP and retain high PKA activity•RIα phase separation is necessary for effective cAMP compartmentation•A PKA oncoprotein disrupts RIα bodies, leading to aberrant signaling and growth
cAMP-responsive condensate formation by PKA’s RIα subunit controls local signaling, and disruption of phase separation in this context contributes to tumorigenesis.
Abstract
There are expected to be ∼10
8
isolated black holes (BHs) in the Milky Way. OGLE-2011-BLG-0462/MOA-2011-BLG-191 (OB110462) is the only such BH with a mass measurement to date. However, its ...mass is disputed: Lam et al. measured a lower mass of 1.6–4.4
M
⊙
, while Sahu et al. and Mróz et al. measured a higher mass of 5.8–8.7
M
⊙
. We reanalyze OB110462, including new data from the Hubble Space Telescope (HST) and rereduced Optical Gravitational Lensing Experiment (OGLE) photometry. We also rereduce and reanalyze the HST data set with newly available software. We find significantly different (∼1 mas) HST astrometry than Lam et al. in the unmagnified epochs due to the amount of positional bias induced by a bright star ∼0.″4 from OB110462. After modeling the updated photometric and astrometric data sets, we find the lens of OB110462 is a
6.0
−
1.0
+
1.2
M
⊙
BH. Future observations with the Nancy Grace Roman Space Telescope, which will have an astrometric precision comparable or better to HST but a field of view 100× larger, will be able to measure hundreds of isolated BH masses via microlensing. This will enable the measurement of the BH mass distribution and improve understanding of massive stellar evolution and BH formation channels.
The star S0-2, which orbits the supermassive black hole (SMBH) in our Galaxy with a period of 16 years, provides the strongest constraint on both the mass of the SMBH and the distance to the Galactic ...center. S0-2 will soon provide the first measurement of relativistic effects near a SMBH. We report the first limits on the binarity of S0-2 from radial velocity (RV) monitoring, which has implications for both understanding its origin and robustness as a probe of the central gravitational field. With 87 RV measurements, which include 12 new observations that we present, we have the requisite data set to look for RV variations from S0-2′s orbital model. Using a Lomb-Scargle analysis and orbit-fitting for potential binaries, we detect no RV variation beyond S0-2′s orbital motion and do not find any significant periodic signal. The lack of a binary companion does not currently distinguish different formation scenarios for S0-2. The upper limit on the mass of a companion star ( ) still allowed by our results has a median upper limit of sin i ≤ 1.6 M for periods between 1 and 150 days, the longest period to avoid tidal break-up of the binary. We also investigate the impact of the remaining allowed binary system on the measurement of the relativistic redshift at S0-2′s closest approach in 2018. While binary star systems are important to consider for this experiment, we find that plausible binaries for S0-2 will not alter a 5 detection of the relativistic redshift.
The general theory of relativity predicts that a star passing close to a supermassive black hole should exhibit a relativistic redshift. In this study, we used observations of the Galactic Center ...star S0-2 to test this prediction. We combined existing spectroscopic and astrometric measurements from 1995-2017, which cover S0-2's 16-year orbit, with measurements from March to September 2018, which cover three events during S0-2's closest approach to the black hole. We detected a combination of special relativistic and gravitational redshift, quantified using the redshift parameter ϒ. Our result, ϒ = 0.88 ± 0.17, is consistent with general relativity (ϒ = 1) and excludes a Newtonian model (ϒ = 0) with a statistical significance of 5σ.
We present a new Milky Way microlensing simulation code, dubbed PopSyCLE (Population Synthesis for Compact object Lensing Events). PopSyCLE is the first resolved microlensing simulation to include a ...compact object distribution derived from numerical supernova explosion models and both astrometric and photometric microlensing effects. We demonstrate the capabilities of PopSyCLE by investigating the optimal way to find black holes (BHs) with microlensing. Candidate BHs have typically been selected from wide-field photometric microlensing surveys, such as OGLE, by selecting events with long Einstein crossing times (tE > 120 days). These events can be selected at closest approach and monitored astrometrically in order to constrain the mass of each lens; PopSyCLE predicts a BH detection rate of ∼40% for such a program. We find that the detection rate can be enhanced to ∼85% by selecting events with both tE > 120 days and a microlensing parallax of πE < 0.08. Unfortunately, such a selection criterion cannot be applied during the event, as πE requires both pre- and post-peak photometry. However, historical microlensing events from photometric surveys can be revisited using this new selection criterion in order to statistically constrain the abundance of BHs in the Milky Way. The future Wide Field Infrared Survey Telescope (WFIRST) microlensing survey provides both precise photometry and astrometry and will yield individual masses of BHs, which is at least an order of magnitude more than is possible with individual candidate follow-up with current facilities. The resulting sample of BH masses from WFIRST will begin to constrain the shape of the BH present-day mass function, BH multiplicity, and BH kick velocity distributions.
The population of young stars near the supermassive black hole (SMBH) in the Galactic Center (GC) has presented an unexpected challenge to theories of star formation. Kinematic measurements of these ...stars have revealed a stellar disk structure (with an apparent 20% disk membership) that has provided important clues regarding the origin of these mysterious young stars. However, many of the apparent disk properties are difficult to explain, including the low disk membership fraction and the high eccentricities given the youth of this population. Thus far, all efforts to derive the properties of this disk have made the simplifying assumption that stars at the GC are single stars. Nevertheless, stellar binaries are prevalent in our Galaxy, and recent investigations suggested that they may also be abundant in the Galactic Center. Here, we show that binaries in the disk can largely alter the apparent orbital properties of the disk. The motion of binary members around each other adds a velocity component, which can be comparable to the magnitude of the velocity around the SMBH in the GC. Thus, neglecting the contribution of binaries can significantly vary the inferred stars' orbital properties. While the disk orientation is unaffected, the apparent disk's 2D width will be increased to about 11 2, similar to the observed width. For a population of stars orbiting the SMBH with zero eccentricity, unaccounted for binaries will create a wide apparent eccentricity distribution with an average of 0.23. This is consistent with the observed average eccentricity of the stars' in the disk. We suggest that this high eccentricity value, which poses a theoretical challenge, may be an artifact of binary stars. Finally, our results suggest that the actual disk membership might be significantly higher than the one inferred by observations that ignore the contribution of binaries, alleviating another theoretical challenge.
Abstract
Gravitational microlensing has the potential to provide direct gravitational masses of single, free-floating brown dwarfs, independent of evolutionary and atmospheric models. The proper ...motions and parallaxes of nearby brown dwarfs can be used to predict close future alignments with distant background stars that cause a microlensing event. Targeted astrometric follow up of the predicted microlensing events permits the brown dwarf’s mass to be measured. Predicted microlensing events are typically found via searching for a peak threshold signal using an estimate of the lens mass. We develop a novel method that finds predicted events that instead will lead to a target lens-mass precision. The main advantage of our method is that it does not require a lens-mass estimate. We use this method to search for predicted astrometric microlensing events occurring between 2014 and 2032 using a catalog of 1225 low-mass star and brown-dwarf lenses in the Solar Neighborhood of spectral type M6 or later and a background source catalog from DECaLS Data Release 9. The background source catalog extends to
g
= 23.95, providing a more dense catalog compared to Gaia. Our search did not reveal any upcoming microlensing events. We estimate the rate of astrometric microlensing event for brown dwarfs in the Legacy Survey and find it to be low ∼10
−5
yr
−1
. We recommend carrying out targeted searches for brown dwarfs in front of the Galactic Bulge and Plane to find astrometric microlensing events that will allow the masses of single, free-floating brown dwarfs to be measured.
Precision measurements of the stars in short-period orbits around the supermassive black hole at the Galactic Center are now being used to constrain general relativistic effects, such as the ...gravitational redshift and periapse precession. One of the largest systematic uncertainties in the measured orbits has been errors in the astrometric reference frame, which is derived from seven infrared-bright stars associated with SiO masers that have extremely accurate radio positions, measured in the Sgr A*-rest frame. We have improved the astrometric reference frame within 14″ of the Galactic Center by a factor of 2.5 in position and a factor of 5 in proper motion. In the new reference frame, Sgr A* is localized to within a position of 0.645 mas and proper motion of 0.03 mas yr−1. We have removed a substantial rotation (2 25 per decade), that was present in the previous less-accurate reference frame used to measure stellar orbits in the field. With our improved methods and continued monitoring of the masers, we predict that orbital precession predicted by general relativity will become detectable in the next ∼5 yr.
The Orion Nebula Cluster (ONC) is the nearest site of ongoing massive star formation, which allows us to study the kinematics and dynamics of the region in detail and constrain star formation ...theories. Using HST ACS/WFPC2/WFC3IR and Keck II NIRC2 data, we have measured the proper motions of 701 stars within an ∼6′ × 6′ field of view around the center of the ONC. We have found more than 10 escaping star candidates, concentrated predominantly at the core of the cluster. The proper motions of the bound stars are consistent with a normal distribution, albeit elongated north-south along the Orion filament, with proper-motion dispersions of mas yr−1 or intrinsic velocity dispersions of km s−1 assuming a distance of 400 pc to the ONC. The cluster shows no evidence for tangential-to-radial anisotropy. Our velocity dispersion profile agrees with the prediction from the observed stellar + gas density profile from Da Rio et al., indicating that the ONC is in virial equilibrium. This finding suggests that the cluster was formed with a low star formation efficiency per dynamical timescale based on comparisons with current star formation theories. Our survey also recovered high-velocity IR sources BN, x and n in the BN/KL region. The estimated location of the first two sources ∼500 yr ago agrees with that of the radio source I, consistent with their proposed common origin from a multistellar disintegration. However, source n appears to have a small proper motion and is unlikely to have been involved in the event.
Abstract
We report the first star formation history study of the Milky Ways nuclear star cluster (NSC), which includes observational constraints from a large sample of stellar metallicity ...measurements. These metallicity measurements were obtained from recent surveys from Gemini and the Very Large Telescope of 770 late-type stars within the central 1.5 pc. These metallicity measurements, along with photometry and spectroscopically derived temperatures, are forward modeled with a Bayesian inference approach. Including metallicity measurements improves the overall fit quality, as the low-temperature red giants that were previously difficult to constrain are now accounted for, and the best fit favors a two-component model. The dominant component contains 93% ± 3% of the mass, is metal-rich (
M
/
H
¯
∼
0.45
), and has an age of
5
−
2
+
3
Gyr, which is ∼3 Gyr younger than earlier studies with fixed (solar) metallicity; this younger age challenges coevolutionary models in which the NSC and supermassive black holes formed simultaneously at early times. The minor population component has low metallicity (
M
/
H
¯
∼
−
1.1
) and contains ∼7% of the stellar mass. The age of the minor component is uncertain (0.1–5 Gyr old). Using the estimated parameters, we infer the following NSC stellar remnant population (with ∼18% uncertainty): 1.5 × 10
5
neutron stars, 2.5 × 10
5
stellar-mass black holes (BHs), and 2.2 × 10
4
BH–BH binaries. These predictions result in 2–4 times fewer neutron stars compared to earlier predictions that assume solar metallicity, introducing a possible new path to understand the so-called “missing-pulsar problem”. Finally, we present updated predictions for the BH–BH merger rates (0.01–3 Gpc
−3
yr
−1
).
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