48 research outputs found
“cAMP Sponge”: A Buffer for Cyclic Adenosine 3′, 5′-Monophosphate
Background: While intracellular buffers are widely used to study calcium signaling, no such tool exists for the other major second messenger, cyclic AMP (cAMP). Methods/Principal Findings: Here we describe a genetically encoded buffer for cAMP based on the high-affinity cAMP-binding carboxy-terminus of the regulatory subunit of protein kinase A (PKA). Addition of targeting sequences permitted localization of this fragment to the extra-nuclear compartment, while tagging with mCherry allowed quantification of its expression at the single cell level. This construct (named “cAMP sponge”) was shown to selectively bind cAMP in vitro. Its expression significantly suppressed agonist-induced cAMP signals and the downstream activation of PKA within the cytosol as measured by FRET-based sensors in single living cells. Point mutations in the cAMP-binding domains of the construct rendered the chimera unable to bind cAMP in vitro or in situ. Cyclic AMP sponge was fruitfully applied to examine feedback regulation of gap junction-mediated transfer of cAMP in epithelial cell couplets. Conclusions: This newest member of the cAMP toolbox has the potential to reveal unique biological functions of cAMP, including insight into the functional significance of compartmentalized signaling events
ISSN exercise & sport nutrition review: research & recommendations
Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients
Avaliação radiográfica da idade óssea em crianças infectadas pelo HIV por via vertical
Inflammatory resolution: New opportunities for drug discovery
Treatment of inflammatory diseases today is largely based on interrupting the synthesis or action
of mediators that drive the host’s response to injury. Non-steroidal anti-inflammatories, steroids
and antihistamines, for instance, were developed on this basis. Although such small-molecule
inhibitors have provided the main treatment for inflammatory arthropathies and asthma, they are
not without their shortcomings. This review offers an alternative approach to the development of
novel therapeutics based on the endogenous mediators and mechanisms that switch off acute
inflammation and bring about its resolution. It is thought that this strategy will open up new
avenues for the future management of inflammation-based diseases
Inhibition of Vasodepressor Neurons in the Caudal Ventrolateral Medulla of the Rabbit Increases Both Arterial-Pressure and the Release of Neuropeptide-Y-Like Immunoreactivity From the Spinal-Cord
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