The Popeye Domain Containing Genes and cAMP Signaling.

3'-5'-cyclic adenosine monophosphate (cAMP) is a second messenger, which plays an important role in the heart. It is generated in response to activation of G-protein-coupled receptors (GPCRs). Initially, it was thought that protein kinase A (PKA) exclusively mediates cAMP-induced cellular responses such as an increase in cardiac contractility, relaxation, and heart rate. With the identification of the exchange factor directly activated by cAMP (EPAC) and hyperpolarizing cyclic nucleotide-gated (HCN) channels as cAMP effector proteins it became clear that a protein network is involved in cAMP signaling. The Popeye domain containing (Popdc) genes encode yet another family of cAMP-binding proteins, which are prominently expressed in the heart. Loss-of-function mutations in mice are associated with cardiac arrhythmia and impaired skeletal muscle regeneration. Interestingly, the cardiac phenotype, which is present in both, Popdc1 and Popdc2 null mutants, is characterized by a stress-induced sinus bradycardia, suggesting that Popdc proteins participate in cAMP signaling in the sinuatrial node. The identification of the two-pore channel TREK-1 and Caveolin 3 as Popdc-interacting proteins represents a first step into understanding the mechanisms of heart rate modulation triggered by Popdc proteins

What is research funding, how does it influence research, and how is it recorded? Key dimensions of variation

Evaluating the effects of some or all academic research funding is difficult because of the many different and overlapping sources, types, and scopes. It is therefore important to identify the key aspects of research funding so that funders and others assessing its value do not overlook them. This article outlines 18 dimensions through which funding varies substantially, as well as three funding records facets. For each dimension, a list of common or possible variations is suggested. The main dimensions include the type of funder of time and equipment, any funding sharing, the proportion of costs funded, the nature of the funding, any collaborative contributions, and the amount and duration of the grant. In addition, funding can influence what is researched, how and by whom. The funding can also be recorded in different places and has different levels of connection to outputs. The many variations and the lack of a clear divide between “unfunded” and funded research, because internal funding can be implicit or unrecorded, greatly complicate assessing the value of funding quantitatively at scale. The dimensions listed here should nevertheless help funding evaluators to consider as many differences as possible and list the remainder as limitations. They also serve as suggested information to collect for those compiling funding datasets

Biallelic expression of Tbx1 protects the embryo from developmental defects caused by increased receptor tyrosine kinase signaling.

BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans, characterized by cardiovascular defects such as interrupted aortic arch, outflow tract defects, thymus and parathyroid hypo- or aplasia, and cleft palate. Heterozygosity of Tbx1, the mouse homolog of the candidate TBX1 gene, results in mild defects dependent on genetic background, whereas complete inactivation results in severe malformations in multiple tissues. RESULTS: The loss of function of two Sprouty genes, which encode feedback antagonists of receptor tyrosine kinase (RTK) signaling, phenocopy many defects associated with 22q11DS in the mouse. The stepwise reduction of Sprouty gene dosage resulted in different phenotypes emerging at specific steps, suggesting that the threshold up to which a given developmental process can tolerate increased RTK signaling is different. Tbx1 heterozygosity significantly exacerbated the severity of all these defects, which correlated with a substantial increase in RTK signaling. CONCLUSIONS: Our findings suggest that TBX1 functions as an essential component of a mechanism that protects the embryo against perturbations in RTK signaling that may lead to developmental defects characteristic of 22q11DS. We propose that genetic factors that enhance RTK signaling ought to be considered as potential genetic modifiers of this syndrome

Direct Observation of Nanoscale Pt Electrode Agglomeration at the Triple Phase Boundary

Nanoporous platinum electrode thin films were delaminated from yttria-stabilized zirconia (YSZ) Substrates via double cantilever beam delamination to reveal the :structure located at the interface between electrode and electrolyte, The thermally driven morphological evolution between the electrode top surface and the substrate contact interface of agglomerated nanoporous platinum thin films were compared. We found the temperature required for significant agglomeration to occur was approximately 100 degrees C higher at the electrolyte contact interface side than at the top Surface side. judging the reaction Active site from the electrode top surface could be inaccurate because higher resistance of thermal agglomeration at the interface could retain the reaction active site during fuel cell operation