346 research outputs found
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Phosphorylation of protein kinase A (PKA) regulatory subunit RIα by protein kinase G (PKG) primes PKA for catalytic activity in cells.
cAMP-dependent protein kinase (PKAc) is a pivotal signaling protein in eukaryotic cells. PKAc has two well-characterized regulatory subunit proteins, RI and RII (each having α and β isoforms), which keep the PKAc catalytic subunit in a catalytically inactive state until activation by cAMP. Previous reports showed that the RIα regulatory subunit is phosphorylated by cGMP-dependent protein kinase (PKG) in vitro, whereupon phosphorylated RIα no longer inhibits PKAc at normal (1:1) stoichiometric ratios. However, the significance of this phosphorylation as a mechanism for activating type I PKA holoenzymes has not been fully explored, especially in cellular systems. In this study, we further examined the potential of RIα phosphorylation to regulate physiologically relevant "desensitization" of PKAc activity. First, the serine 101 site of RIα was validated as a target of PKGIα phosphorylation both in vitro and in cells. Analysis of a phosphomimetic substitution in RIα (S101E) showed that modification of this site increases PKAc activity in vitro and in cells, even without cAMP stimulation. Numerous techniques were used to show that although Ser101 variants of RIα can bind PKAc, the modified linker region of the S101E mutant has a significantly reduced affinity for the PKAc active site. These findings suggest that RIα phosphorylation may be a novel mechanism to circumvent the requirement of cAMP stimulus to activate type I PKA in cells. We have thus proposed a model to explain how PKG phosphorylation of RIα creates a "sensitized intermediate" state that is in effect primed to trigger PKAc activity
Light actuated remote control security system
A remote control security apparatus includes a lock element movable between locked and unlocked positions by an electrically actuated power device. The operator is provided with a portable transmitter adapted to generate light which is interrupted at a predetermined frequency so as to produce an encoded light signal. This signal is detected by a light transceiver which generates an independent signal at the same predetermined frequency and which compares the frequencies of the detected signal and independent signal. If these frequencies are substantially the same, the transceiver actuates the power means to move the lock element to its unlocked position. The security apparatus may be advantageously installed as a door lock, in which case a lock element receiving member is secured to the door. The signal detector is positioned at the exterior side of the door for receiving encoded signals from the transmitter and an override switch may be positioned at an interior side of the door for opening the lock without a transmitter. A contact switch is disclosed which maintains the lock element in the unlocked position whenever the door is open
US women's choices of strategies to protect themselves from violence
To examine the extent to which US women's self‐protection strategies are associated with either their personal or vicarious victimization experiences
Validation of X-ray fluorescence-measured Swine femur lead against atomic absorption spectrometry.
The aim of this study was to apply the technique of (109)Cd-based K-shell X-ray fluorescence (XRF) bone lead measurements to swine femurs and to validate the concentrations obtained therefrom against an independent chemical measurement of bone lead: atomic absorption spectrometry (AAS). The femurs ranged in lead concentration from 1.0 to 24.5 microg of lead per gram of ashed bone, as measured by AAS. On average, XRF overestimated AAS-measured femur lead by 2.6 microg/g [95% confidence interval (CI), 1.1-4.0 microg/g], approximately 2 microg/g poorer than that observed in studies of human tibiae. Measurements of swine femur and, by extension, of nonhuman bones may require adjustment of the XRF spectrum peak extraction method
Src activation by cGMP/PKG II in osteoblasts: characterization of a mechano-sensitive signalling complex
The first crystal structure of cyclic GMP-dependent protein kinase Iβ dimerization/docking domain reveals molecular details of isoform-specific anchoring
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Aortic pathology from protein kinase G activation is prevented by an antioxidant vitamin B12 analog.
People heterozygous for an activating mutation in protein kinase G1 (PRKG1, p.Arg177Gln) develop thoracic aortic aneurysms and dissections (TAAD) as young adults. Here we report that mice heterozygous for the mutation have a three-fold increase in basal protein kinase G (PKG) activity, and develop age-dependent aortic dilation. Prkg1R177Q/+ aortas show increased smooth muscle cell apoptosis, elastin fiber breaks, and oxidative stress compared to aortas from wild type littermates. Transverse aortic constriction (TAC)-to increase wall stress in the ascending aorta-induces severe aortic pathology and mortality from aortic rupture in young mutant mice. The free radical-neutralizing vitamin B12-analog cobinamide completely prevents age-related aortic wall degeneration, and the unrelated anti-oxidant N-acetylcysteine ameliorates TAC-induced pathology. Thus, increased basal PKG activity induces oxidative stress in the aorta, raising concern about the widespread clinical use of PKG-activating drugs. Cobinamide could be a treatment for aortic aneurysms where oxidative stress contributes to the disease, including Marfan syndrome
Soybean Management for Seed Composition: The Perspective of U.S. Farmers
The soybean [Glycine max (L.) Merr.] compositional quality is mainly provided by the seed concentration of protein and oil. These traits are critical for sustaining global use, and although there is demand for high protein soybean, no mechanism to differentiate production is in place. At the opposite end of the supply chain, farmers are remunerated on a mass basis without having any incentive regarding seed composition. This study evaluated farmers\u27 perspectives and knowledge on soybean quality and their propensity to adopt quality improvement technologies. Farmers from the main U.S. producing regions (n = 271) were investigated with a self-administrated survey containing 21 questions during 2020 and 2021. Our results show that 84% are unaware of the current protein and oil levels from their own production. A small portion (1.4%) make management decisions (e.g., choice of genotypes or monitor quality) based on the implications on seed quality. However, practices already in place are likely to enhance the quality of seed, namely N nutrition (via rhizobia [12.9%] or fertilizer [5.9%]) and late-season crop protection (17.1%). If farmers are financially rewarded by US$0.50 per bushel, a mindset change may occur. Based on these results, we concluded that shifts in the U.S. production system targeting protein or oil markets are possible, and the constraints are mainly related to on-farm management. However, the challenges for improving the U.S. soybean competitiveness in global or niche markets also rely upon other segments of the production chain, specifically breeders, technology suppliers, and logistical structure
Incorporating lessons from high-input research into a low-margin year
Increased soybean commodity prices in recent years have generated interest in developing high-input systems to increase yield. However, little information exists about the effects of input-intensive, high-yield management on soybean yield and profitability, as well as interactions with basic agronomic practices
Black-white discrimination and orienting behavior in the desert iguana (Dipsosaurus dorsalis)
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