Variability and memory of protein levels in human cells

Protein expression is a stochastic process that leads to phenotypic variation among cells. The cell-cell distribution of protein levels in microorganisms has been well characterized but little is known about such variability in human cells. Here, we studied the variability of protein levels in human cells, as well as the temporal dynamics of this variability, and addressed whether cells with higher than average protein levels eventually have lower than average levels, and if so, over what timescale does this mixing occur. We measured fluctuations over time in the levels of 20 endogenous proteins in living human cells, tagged by the gene for yellow fluorescent protein at their chromosomal loci. We found variability with a standard deviation that ranged, for different proteins, from about 15% to 30% of the mean. Mixing between high and low levels occurred for all proteins, but the mixing time was longer than two cell generations (more than 40 h) for many proteins. We also tagged pairs of proteins with two colours, and found that the levels of proteins in the same biological pathway were far more correlated than those of proteins in different pathways. The persistent memory for protein levels that we found might underlie individuality in cell behaviour and could set a timescale needed for signals to affect fully every member of a cell population.     

Tail-assisted pitch control in lizards, robots and dinosaurs

In 1969, a palaeontologist proposed that theropod dinosaurs used their tails as dynamic stabilizers during rapid or irregular movements, contributing to their depiction as active and agile predators. Since then the inertia of swinging appendages has been implicated in stabilizing human walking, aiding acrobatic manoeuvres by primates and rodents, and enabling cats to balance on branches. Recent studies on geckos suggest that active tail stabilization occurs during climbing, righting and gliding. By contrast, studies on the effect of lizard tail loss show evidence of a decrease, an increase or no change in performance. Application of a control-theoretic framework could advance our general understanding of inertial appendage use in locomotion. Here we report that lizards control the swing of their tails in a measured manner to redirect angular momentum from their bodies to their tails, stabilizing body attitude in the sagittal plane. We video-recorded Red-Headed Agama lizards (Agama agama) leaping towards a vertical surface by first vaulting onto an obstacle with variable traction to induce a range of perturbations in body angular momentum. To examine a known controlled tail response, we built a lizard-sized robot with an active tail that used sensory feedback to stabilize pitch as it drove off a ramp. Our dynamics model revealed that a body swinging its tail experienced less rotation than a body with a rigid tail, a passively compliant tail or no tail. To compare a range of tails, we calculated tail effectiveness as the amount of tailless body rotation a tail could stabilize. A model Velociraptor mongoliensis supported the initial tail stabilization hypothesis, showing as it did a greater tail effectiveness than the Agama lizards. Leaping lizards show that inertial control of body attitude can advance our understanding of appendage evolution and provide biological inspiration for the next generation of manoeuvrable search-and-rescue robots.     

The sirtuin SIRT6 regulates lifespan in male mice

The significant increase in human lifespan during the past century confronts us with great medical challenges. To meet these challenges, the mechanisms that determine healthy ageing must be understood and controlled. Sirtuins are highly conserved deacetylases that have been shown to regulate lifespan in yeast, nematodes and fruitflies. However, the role of sirtuins in regulating worm and fly lifespan has recently become controversial. Moreover, the role of the seven mammalian sirtuins, SIRT1 to SIRT7 (homologues of the yeast sirtuin Sir2), in regulating lifespan is unclear. Here we show that male, but not female, transgenic mice overexpressing Sirt6 (ref. 4) have a significantly longer lifespan than wild-type mice. Gene expression analysis revealed significant differences between male Sirt6-transgenic mice and male wild-type mice: transgenic males displayed lower serum levels of insulin-like growth factor 1 (IGF1), higher levels of IGF-binding protein 1 and altered phosphorylation levels of major components of IGF1 signalling, a key pathway in the regulation of lifespan. This study shows the regulation of mammalian lifespan by a sirtuin family member and has important therapeutic implications for age-related diseases.     

Vortex dynamics in superconducting MgB2 and prospects for applications

The recently discovered superconductor magnesium diboride, MgB2, has a transition temperature, Tc, approaching 40 K, placing it intermediate between the families of low- and high-temperature superconductors. In practical applications, superconductors are permeated by quantized vortices of magnetic flux. When a supercurrent flows, there is dissipation of energy unless these vortices are 'pinned' in some way, and so inhibited from moving under the influence of the Lorentz force. Such vortex motion ultimately determines the critical current density, Jc, which the superconductor can support. Vortex behaviour has proved to be more complicated in high-temperature superconductors than in low-temperature superconductors and, although this has stimulated extensive theoretical and experimental research, it has also impeded applications. Here we describe the vortex behaviour in MgB2, as reflected in Jc and in the vortex creep rate, S, the latter being a measure of how fast the 'persistent' supercurrents decay. Our results show that naturally occurring grain boundaries are highly transparent to supercurrents, a desirable property which contrasts with the behaviour of the high-temperature superconductors. On the other hand, we observe a steep, practically deleterious decline in Jc with increasing magnetic field, which is likely to reflect the high degree of crystalline perfection in our samples, and hence a low vortex pinning energy.     

Detachment fronts and the onset of dynamic friction

The dynamics of friction have been studied for hundreds of years, yet many aspects of these everyday processes are not understood. One such aspect is the onset of frictional motion (slip). First described more than 200 years ago as the transition from static to dynamic friction, the onset of slip is central to fields as diverse as physics, tribology, mechanics of earthquakes and fracture. Here we show that the onset of frictional slip is governed by three different types of coherent crack-like fronts: these are observed by real-time visualization of the net contact area that forms the interface separating two blocks of like material. Two of these fronts, which propagate at subsonic and intersonic velocities, have been the subject of intensive recent interest. We show that a third type of front, which propagates an order of magnitude more slowly, is the dominant mechanism for the rupture of the interface. No overall motion (sliding) of the blocks occurs until either of the slower two fronts traverses the entire interface.