44 research outputs found
MyBP-C: one protein to govern them all
The heart is an extraordinarily versatile pump, finely tuned to respond to a multitude of demands. Given the heart pumps without rest for decades its efficiency is particularly relevant. Although many proteins in the heart are essential for viability, the non-essential components can attract numerous mutations which can cause disease, possibly through alterations in pumping efficiency. Of these, myosin binding protein C is strongly over-represented with ~ 40% of all known mutations in hypertrophic cardiomyopathy. Therefore, a complete understanding of its molecular function in the cardiac sarcomere is warranted. In this review, we revisit contemporary and classical literature to clarify both the current standing of this fast-moving field and frame future unresolved questions. To date, much effort has been directed at understanding MyBP-C function on either thick or thin filaments. Here we aim to focus questions on how MyBP-C functions at a molecular level in the context of both the thick and thin filaments together. A concept that emerges is MyBP-C acts to govern interactions on two levels; controlling myosin access to the thin filament by sequestration on the thick filament, and controlling the activation state and access of myosin to its binding sites on the thin filament. Such affects are achieved through directed interactions mediated by phosphorylation (of MyBP-C and other sarcomeric components) and calcium
Can we improve outcome of congenital diaphragmatic hernia?
This review gives an overview of the disease spectrum of congenital diaphragmatic hernia (CDH). Etiological factors, prenatal predictors of survival, new treatment strategies and long-term morbidity are described. Early recognition of problems and improvement of treatment strategies in CDH patients may increase survival and prevent secondary morbidity. Multidisciplinary healthcare is necessary to improve healthcare for CDH patients. Absence of international therapy guidelines, lack of evidence of many therapeutic modalities and the relative low number of CDH patients calls for cooperation between centers with an expertise in the treatment of CDH patients. The international CDH Euro-Consortium is an example of such a collaborative network, which enhances exchange of knowledge, future research and development of treatment protocols
High-Pressure Methane Adsorption and Characterization of Pores in Posidonia Shales and Isolated Kerogens
The NANOGrav 15-year Data Set: Evidence for a Gravitational-Wave Background
We report multiple lines of evidence for a stochastic signal that is
correlated among 67 pulsars from the 15-year pulsar-timing data set collected
by the North American Nanohertz Observatory for Gravitational Waves. The
correlations follow the Hellings-Downs pattern expected for a stochastic
gravitational-wave background. The presence of such a gravitational-wave
background with a power-law-spectrum is favored over a model with only
independent pulsar noises with a Bayes factor in excess of , and this
same model is favored over an uncorrelated common power-law-spectrum model with
Bayes factors of 200-1000, depending on spectral modeling choices. We have
built a statistical background distribution for these latter Bayes factors
using a method that removes inter-pulsar correlations from our data set,
finding (approx. ) for the observed Bayes factors in the
null no-correlation scenario. A frequentist test statistic built directly as a
weighted sum of inter-pulsar correlations yields (approx. ). Assuming a fiducial
characteristic-strain spectrum, as appropriate for an ensemble of binary
supermassive black-hole inspirals, the strain amplitude is (median + 90% credible interval) at a reference frequency of
1/(1 yr). The inferred gravitational-wave background amplitude and spectrum are
consistent with astrophysical expectations for a signal from a population of
supermassive black-hole binaries, although more exotic cosmological and
astrophysical sources cannot be excluded. The observation of Hellings-Downs
correlations points to the gravitational-wave origin of this signal.Comment: 30 pages, 18 figures. Published in Astrophysical Journal Letters as
part of Focus on NANOGrav's 15-year Data Set and the Gravitational Wave
Background. For questions or comments, please email [email protected]
New Developments in NMR
Regulating protein states is considered the core function of chaperones. However, despite their importance to all major cellular processes, the conformational changes that chaperones impart on polypeptide chains are difficult to study directly due to their heterogeneous, dynamic, and multi-step nature. Here, we review recent advances towards this aim using single-molecule manipulation methods, which are rapidly revealing new mechanisms of conformational control and helping to define a different perspective on the chaperone function