89 research outputs found
What is in a pebble shape?
We propose to characterize the shapes of flat pebbles in terms of the
statistical distribution of curvatures measured along the pebble contour. This
is demonstrated for the erosion of clay pebbles in a controlled laboratory
apparatus. Photographs at various stages of erosion are analyzed, and compared
with two models. We find that the curvature distribution complements the usual
measurement of aspect ratio, and connects naturally to erosion processes that
are typically faster at protruding regions of high curvature.Comment: Phys. Rev. Lett. (to appear
The shape and erosion of pebbles
The shapes of flat pebbles may be characterized in terms of the statistical
distribution of curvatures measured along their contours. We illustrate this
new method for clay pebbles eroded in a controlled laboratory apparatus, and
also for naturally-occurring rip-up clasts formed and eroded in the Mont
St.-Michel bay. We find that the curvature distribution allows finer
discrimination than traditional measures of aspect ratios. Furthermore, it
connects to the microscopic action of erosion processes that are typically
faster at protruding regions of high curvature. We discuss in detail how the
curvature may be reliable deduced from digital photographs.Comment: 10 pages, 11 figure
MARK4 controls ischaemic heart failure through microtubule detyrosination.
Myocardial infarction is a major cause of premature death in adults. Compromised cardiac function after myocardial infarction leads to chronic heart failure with systemic health complications and a high mortality rate1. Effective therapeutic strategies are needed to improve the recovery of cardiac function after myocardial infarction. More specifically, there is a major unmet need for a new class of drugs that can improve cardiomyocyte contractility, because inotropic therapies that are currently available have been associated with high morbidity and mortality in patients with systolic heart failure2,3 or have shown a very modest reduction of risk of heart failure4. Microtubule detyrosination is emerging as an important mechanism for the regulation of cardiomyocyte contractility5. Here we show that deficiency of microtubule-affinity regulating kinase 4 (MARK4) substantially limits the reduction in the left ventricular ejection fraction after acute myocardial infarction in mice, without affecting infarct size or cardiac remodelling. Mechanistically, we provide evidence that MARK4 regulates cardiomyocyte contractility by promoting phosphorylation of microtubule-associated protein 4 (MAP4), which facilitates the access of vasohibin 2 (VASH2)-a tubulin carboxypeptidase-to microtubules for the detyrosination of α-tubulin. Our results show how the detyrosination of microtubules in cardiomyocytes is finely tuned by MARK4 to regulate cardiac inotropy, and identify MARK4 as a promising therapeutic target for improving cardiac function after myocardial infarction.BHF fellowship grant (FS/14/28/30713), Issac Newton Trust Grant (18.40u), and Cambridge BHF Centre of Research Excellence grants (RE/13/6/30180 and RE/18/1/34212)
G-protein signaling: back to the future
Heterotrimeric G-proteins are intracellular partners of G-protein-coupled receptors (GPCRs). GPCRs act on inactive Gα·GDP/Gβγ heterotrimers to promote GDP release and GTP binding, resulting in liberation of Gα from Gβγ. Gα·GTP and Gβγ target effectors including adenylyl cyclases, phospholipases and ion channels. Signaling is terminated by intrinsic GTPase activity of Gα and heterotrimer reformation — a cycle accelerated by ‘regulators of G-protein signaling’ (RGS proteins). Recent studies have identified several unconventional G-protein signaling pathways that diverge from this standard model. Whereas phospholipase C (PLC) β is activated by Gαq and Gβγ, novel PLC isoforms are regulated by both heterotrimeric and Ras-superfamily G-proteins. An Arabidopsis protein has been discovered containing both GPCR and RGS domains within the same protein. Most surprisingly, a receptor-independent Gα nucleotide cycle that regulates cell division has been delineated in both Caenorhabditis elegans and Drosophila melanogaster. Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways
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