We present the results of 7 years of K-band monitoring of the low-mass X-ray binary GRS 1915+105. Positive correlations between the infrared flux and the X-ray flux and X-ray hardness are ...demonstrated. Analysis of the frequency spectrum shows that the orbital period of the system is P sub(orb) = 30.8 c 0.2 days. The phase and amplitude of the orbital modulation suggests that the modulation is due to the heating of the face of the secondary star. We also report another periodic signature between 31.2 and 31.6 days, most likely due to a superhump resonance. From the superhump period we then obtain a range for the mass ratio of the system, 0.05 < q < 0.12.
WNK (with no lysine K) protein kinases were named for their unique active site organization. Mutations in WNK1 and WNK4 cause a familial form of hypertension by undefined mechanisms. Here, we report ...that WNK1 selectively binds to and phosphorylates synaptotagmin 2 (Syt2) within its calcium binding C2 domains. Endogenous WNK1 and Syt2 coimmunoprecipitate and colocalize on a subset of secretory granules in INS-1 cells. Phosphorylation by WNK1 increases the amount of Ca2+ required for Syt2 binding to phospholipid vesicles; mutation of threonine 202, a WNK1 phosphorylation site, partially prevents this change. These findings suggest that phosphorylation of Syts by WNK1 can regulate Ca2+ sensing and the subsequent Ca2+-dependent interactions mediated by Syt C2 domains. These findings provide a biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. Interruption of this regulatory pathway may disturb membrane events that regulate ion balance.
The purpose of the present study was to examine the ability of Black racial identity to mediate cardiovascular reactivity to racism. The Multidimensional Model of Racial Identity (MMRI), which ...consists of four dimensions, salience, centrality, regard, and ideology was used to define Black racial identity. The subdimensions of ideology are oppressed minority, nationalist, humanist, and assimilationist racial identities.
Heart rate, cardiac output, stroke volume, and blood pressure were measured in 72 African-American men as they viewed a videotaped scene depicting racial profiling and a neutral scene. We hypothesized that individuals with high levels of Black-oriented identities (centrality, public regard, private regard, oppressed minority, and nationalist) would be less stressed by the racial profiling scenes than those low in these identities. In addition, we predicted that individuals with high levels of non-Black-oriented identities (assimilationist, humanist) would be more stressed by the racial profiling scenes than those with low levels of these identities.
Private regard, humanist, and assimilationist racial identities were significantly associated with increased cardiovascular reactivity to the scenes. Specifically, private regard significantly predicted cardiac output and stroke volume responses to the scenes. In addition, assimilationist and humanist racial identities were associated with greater blood output and faster heart rates in response to the scenes.
Although private regard (Black oriented) and assimilationist and humanist (non- Black oriented) racial identities showed elevated cardiovascular reactivity to the scenes, the underlying mechanisms of these associations may differ.
The WNK kinases are a recently discovered family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis, lntronic deletions in the ...WNK1 gene resuk in its overexpression and lead to pseudohypoaldosteronism type Ⅱ, a disease with salt-sensitive hypertension and hyperkalemia. This review focuses on the recent evidence elucidating the structure of the kinase domain of WNK1 and functions of these kinases in normal and disease physiology. Their functions have implications for understanding the biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. The WNK kinases may be able to influence ion homeostasis through its effects on synaptotagmin function.
Docking between MEK1 and ERK2 is required for their stable interaction and efficient signal transmission. The MEK1 N terminus contains the ERK docking or D domain that consists of conserved ...hydrophobic and basic residues. We mutated the hydrophobic and basic residues individually and found that loss of either type reduced MEK1 phosphorylation of ERK2 in vitroand its ability to bind to ERK2 in vivo. Moreover, ERK2 was localized in both the cytoplasm and the nucleus when co-expressed with MEK1 that had mutations in either the hydrophobic or the basic residues. We then identified two conserved hydrophobic residues on ERK2 that play roles in docking with MEK1. Mutating these residues to alanine reduced the interaction of ERK2 with MEK1 in cells. These mutations also reduced the phosphorylation of MEK1 by ERK2 but had little effect on phosphorylation of MBP by ERK2. Finally, we generated docking site mutants in ERK2-MEK1 fusion proteins. Although the mutation of the MEK1 D domain significantly reduced ERK2-MEK1 activity, mutations of the putatively complementary acidic residues and hydrophobic residues on ERK2 did not change its activity. However, both types of mutations decreased the phosphorylation of Elk-1 caused by ERK2-MEK1 fusion proteins. These findings suggest complex interactions of MEK1 D domains with ERK2 that influence its activation and its effects on substrates.
Inhibition of Glucose-Stimulated Activation of Extracellular Signal–Regulated Protein Kinases 1 and 2 by Epinephrine in Pancreatic
β-Cells
Tara Beers Gibson 1 ,
Michael C. Lawrence 1 ,
Craig J. ...Gibson 2 ,
Colleen A. Vanderbilt 1 ,
Kathleen McGlynn 1 ,
Don Arnette 1 ,
Wei Chen 1 ,
Julie Collins 1 ,
Bashoo Naziruddin 3 ,
Marlon F. Levy 3 ,
Barbara E. Ehrlich 2 and
Melanie H. Cobb 1
1 Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
2 Departments of Pharmacology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut
3 cGMP Islet Cell Processing Laboratory, Islet Cell Transplant Program, Baylor University Medical Center, Dallas, Texas
Address correspondence and reprint requests to Melanie H. Cobb, Department of Pharmacology, UT Southwestern Medical Center,
6001 Forest Park Rd., Dallas, TX 75390-9041. E-mail: melanie.cobb{at}utsouthwestern.edu
Abstract
Glucose sensing is essential for the ability of pancreatic β-cells to produce insulin in sufficient quantities to maintain
blood glucose within the normal range. Stress causes the release of adrenergic hormones that increase circulating glucose
by promoting glucose production and inhibiting insulin release. We have shown that extracellular signal–regulated kinases
1 and 2 (ERK1/2) are responsive to glucose in pancreatic β-cells and that glucose activates ERK1/2 by mechanisms independent
of insulin. Here we show that glucose-induced activation of ERK1/2 is inhibited by epinephrine through the α 2 -adrenergic receptor. Epinephrine and the selective α 2 -adrenergic agonist UK14304 reduced insulin secretion and glucose-stimulated ERK1/2 activation in a pertussis toxin–sensitive
manner, implicating the α subunit of a Gi family member. α 2 -adrenergic agonists also reduced stimulation of ERK1/2 by glucagon-like peptide 1 and KCl, but not by phorbol ester or nerve
growth factor. Our findings suggest that α 2 -adrenergic agonists act via a Gi family member on early steps in ERK1/2 activation, supporting the idea that ERK1/2 are regulated
in a manner that reflects insulin demand.
ER, endoplasmic reticulum
ERK1/2, extracellular signal–regulated kinases 1 and 2
GLP, glucagon-like peptide
KRBH, Krebs-Ringer bicarbonate HEPES
MAP, mitogen-activated protein
PKA, protein kinase A
SERCA, sarcoplasmic reticulum/endoplasmic reticulum ATPase
Footnotes
W.C. is currently affiliated with the National Institute of Biological Sciences, Beijing, China.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted January 17, 2006.
Received September 27, 2005.
DIABETES
An ERK2-binding site at the N terminus of MEK1 was reported to mediate their stable association. We examined the importance
of this binding site in the feedback phosphorylation of MEK1 on Thr 292 and ...Thr 386 by ERK2, the phosphorylation and activation of ERK2 by MEK1, and the interaction of MEK1 with ERK2 and Raf-1. Deletion of
the binding site from MEK1 reduced its phosphorylation by ERK2, but had no effect on its phosphorylation by p21-activated
protein kinase-1 (PAK1). A MEK1 N-terminal peptide containing the binding site inhibited MEK1 phosphorylation by ERK2. However,
it did not affect MEK1 phosphorylation by p21-activated protein kinase or myelin basic protein phosphorylation by ERK2. Deletion
of the N-terminal ERK-binding domain of MEK1 also reduced its ability to phosphorylate ERK2 in vitro , to co-immunoprecipitate with ERK2, and to stimulate ERK2 activation in transfected cells, but it did not alter the association
with endogenous Raf-1. Using ERK2-p38 chimeras and an ERK2 deletion mutant, a MEK1-binding site of ERK2 was localized to its
N terminus.
Abstract Purpose Prior studies of anxiety and depression among families of intensive care unit patients excluded those admitted for less than 2 days. We hypothesized that families of surviving ...patients with length of stay less than 2 days would have similar prevalence of anxiety and depression compared with those admitted for longer. Materials and methods One hundred six family members in the neurosciences and medical intensive care units at a university hospital completed the Hospital Anxiety and Depression Scale at discharge. Results The 106 participants represented a response rate of 63.9% among those who received surveys. Fifty-eight surveys (54.7%) were from relatives of patients who were discharged within 2 days of admission, whereas 48 (45.3%) were from those admitted for longer. No difference in anxiety was detected; prevalence was 20.7% (95% confidence interval, 10.4) among shorter stay families and 8.3% (7.8) among longer stay families ( P = .10). No difference was also seen with depression; prevalence was 8.6% (7.2) among shorter stay families and 4.2% (5.7) among longer stay families ( P = .45). Conclusions Families of surviving patients with brief length of stay may have similar prevalence of anxiety and depression at discharge to those with longer length of stay.
Here, we report the discovery of a kilonova associated with the nearby (350 Mpc) minute-duration GRB 211211A. In tandem with deep optical limits that rule out the presence of an accompanying ...supernova to \(M_I > -13\) mag at 17.7 days post-burst, the identification of a kilonova confirms that this burst's progenitor was a compact object merger. While the spectrally softer tail in GRB 211211A's gamma-ray light curve is reminiscent of previous extended emission short GRBs (EE-SGRBs), its prompt, bright spikes last \(\gtrsim 12\) s, separating it from past EE-SGRBs. GRB 211211A's kilonova has a similar luminosity, duration and color to AT2017gfo, the kilonova found in association with the gravitational wave (GW)-detected binary neutron star (BNS) merger GW170817. We find that the merger ejected \(\approx 0.04 M_{\odot}\) of r-process-rich material, and is consistent with the merger of two neutron stars (NSs) with masses close to the canonical \(1.4 M_{\odot}\). This discovery implies that GRBs with long, complex light curves can be spawned from compact object merger events and that a population of kilonovae following GRBs with durations \(\gg 2\) s should be accounted for in calculations of the NS merger r-process contribution and rate. At 350 Mpc, the current network of GW interferometers at design sensitivity would have detected the merger precipitating GRB 211211A, had it been operating at the time of the event. Further searches for GW signals coincident with long GRBs are therefore a promising route for future multi-messenger astronomy.
Aims. With this paper we want to investigate the highly variable afterglow light curve and environment of gamma-ray burst (GRB) 060526 at z = 3.221. Methods. We present one of the largest photometric ...datasets ever obtained for a GRB afterglow, consisting of multi-color photometric data from the ultraviolet to the near infrared. The data set contains 412 data points in total to which we add additional data from the literature. Furthermore, we present low-resolution high signal-to-noise spectra of the afterglow. The afterglow light curve is modeled with both an analytical model using broken power law fits and with a broad-band numerical model which includes energy injections. The absorption lines detected in the spectra are used to derive column densities using a multi-ion single-component curve-of-growth analysis from which we derive the metallicity of the host of GRB 060526. Results. The temporal behaviour of the afterglow follows a double broken power law with breaks at t = 0.090 ± 0.005 and t = 2.401 ± 0.061 days. It shows deviations from the smooth set of power laws that can be modeled by additional energy injections from the central engine, although some significant microvariability remains. The broadband spectral-energy distribution of the afterglow shows no significant extinction along the line of sight. The metallicity derived from S ii and Fe ii of S/H = –0.57 ± 0.25 and Fe/H = –1.09 ± 0.24 is relatively high for a galaxy at that redshift but comparable to the metallicity of other GRB hosts at similar redshifts. At the position of the afterglow, no host is detected to F775W(AB) = 28.5 mag with the HST, implying an absolute magnitude of the host M(1500 Å) > –18.3 mag which is fainter than most long-duration hosts, although the GRB may be associated with a faint galaxy at a distance of 11 kpc.
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