Calcium channel blockers accelerate aortic aneurysm and cause premature aortic rupture in a mouse model of Marfan syndrome through protein kinase C-mediated activation of extracellular signal-regulated kinase.
Structures of the replicative DNA polymerase Pol IIIα, the DNA sliding clamp, the proofreading exonuclease, and the processivity switch Tau (τ) suggest a mechanism for quick release during lagging strand synthesis.
X-ray crystallography reveals that the Dna2 nuclease-helicase contains a long tunnel through which single-stranded DNA threads, and an allosteric mechanism for displacing the DNA-binding protein Rpa that restricts cleavage to the proper polarity.
Digital NF-κB signaling achieves orthogonal control over the probability of activation (percentage of activated cells) and dynamic response heterogeneity in the population via the area and shape of the input profile.
Control of neural stem cells by reactive oxygen species (ROS) provides a link between systemic shifts in oxygen tension and neuronal regeneration, and suggests an evolutionary driving force for the inherent ability of newts to regenerate their brain cells.
Neural progenitors reside in relative low oxygen in the subgranular zone (SGZ), and the higher tissue oxygen levels that these cells must face as they migrate away from the hypoxic areas and differentiate appear to cause oxidative damage and an early phase of cell death.
A novel computation tool for microbial community modeling predicts the evolution and diversification of E. coli in laboratory evolution experiments and gives insight into the underlying metabolic processes.
The newly discovered Titin internal promoter may explain why the severity of dilated cardiomyopathy in patients with truncating mutations in Titin varies dramatically depending on position of the mutation.
Chromatin structure is altered following DNA replication stress through the activity of protein kinase C signalling which leads to functionally coupled histone H3 phosphorylation and acetylation events.
Asymmetric cell division is linked to cell-specific transcription by handoff of a key developmental regulator from the cytokinetic machinery to the adjacent cell pole where it oligomerizes to become stabilized and activated.
Two classes of premotor inhibitory neurons have specific roles in controlling flexor-extensor behaviors in mice, which is the underlying neural mechanism for limb driven movements in terrestrial vertebrates.
A long-term evolution experiment with Escherichia coli shows that the appearance and optimization of a new trait can require both co-opting existing cellular pathways for new roles and reversing a history of previous adaptation.
During quiet wakefulness but not slow wave sleep, reward modulated VTA neurons coordinate selectively with hippocampal replay sequences and are biased in their timing towards the reactivated representation of reward locations.
Preclinical efficacy experiments testing sunitinib in animal cancer models display a lack of methodological rigour, with trim-and-fill analysis suggesting prominent publication bias that leads to an overestimation of treatment effect.
Mutational analysis and biochemical experiments suggest that the conserved β-hairpin-like membrane-reentrant loop of RseP - an S2P family intramembrane cleaving protease - helps to discriminate substrates by directly interacting with their transmembrane segments.
Mouse genetic studies reveal that let-7 performs potent tumor suppressive roles, but at the expense of regeneration and tissue homeostasis in the liver, findings with unanticipated therapeutic implications.
Structural analysis of the ATP synthase – in combination with evolutionary covariance analysis – reveals the fold of the a subunit and shows that the enzyme can adopt several different conformations, which support the Brownian ratchet model for generating rotation.
Despite the widely held belief among researchers in consciousness that healthy observers can show unconscious perception, a study using a novel method to control for response biases finds no evidence for this phenomenon.
Analysis of 3D paw kinematics and whole-body coordination in freely walking mice isolates specific features of gait ataxia and supports the hypothesis that the cerebellum provides an internal forward model for motor control.
Rapid forward engineering can be accomplished using cell-free systems, as demonstrated by the implementation and characterization of novel genetic oscillators in a cell-free system and their consequent transfer to cells.
Comprehensive gene profiling of the hypothalamic hypocretin neurons, high resolution imaging and behavioral assays have revealed the molecular signature of these versatile neurons and identified a potassium channel that is required for nighttime sleep.