Regulation of the H<Superscript>+</Superscript>-ATP synthase by IF1: a role in mitohormesis

The mitochondrial H⁺-ATP synthase is a primary hub of cellular homeostasis by providing the energy required to sustain cellular activity and regulating the production of signaling molecules that reprogram nuclear activity needed for adaption to changing cues. Herein, we summarize findings regarding the regulation of the activity of the H⁺-ATP synthase by its physiological inhibitor, the ATPase inhibitory factor 1 (IF1) and their functional role in cellular homeostasis. First, we outline the structure and the main molecular mechanisms that regulate the activity of the enzyme. Next, we describe the molecular biology of IF1 and summarize the regulation of IF1 expression and activity as an inhibitor of the H⁺-ATP synthase emphasizing the role of IF1 as a main driver of energy rewiring and cellular signaling in cancer. Findings in transgenic mice in vivo indicate that the overexpression of IF1 is sufficient to reprogram energy metabolism to an enhanced glycolysis and activate reactive oxygen species (ROS)-dependent signaling pathways that promote cell survival. These findings are placed in the context of mitohormesis, a program in which a mild mitochondrial stress triggers adaptive cytoprotective mechanisms that improve lifespan. In this regard, we emphasize the role played by the H⁺-ATP synthase in modulating signaling pathways that activate the mitohormetic response, namely ATP, ROS and target of rapamycin (TOR). Overall, we aim to highlight the relevant role of the H⁺-ATP synthase and of IF1 in cellular physiology and the need of additional studies to decipher their contributions to aging and age-related diseases.     

Routes and machinery of primary cilium biogenesis

Primary cilia are solitary, microtubule-based protrusions of the cell surface that play fundamental roles as photosensors, mechanosensors and biochemical sensors. Primary cilia dysfunction results in a long list of developmental and degenerative disorders that combine to give rise to a large spectrum of human diseases affecting almost any major body organ. Depending on the cell type, primary ciliogenesis is initiated intracellularly, as in fibroblasts, or at the cell surface, as in renal polarized epithelial cells. In this review, we have focused on the routes of primary ciliogenesis placing particular emphasis on the recently described pathway in renal polarized epithelial cells by which the midbody remnant resulting from a previous cell division event enables the centrosome for initiation of primary cilium assembly. The protein machinery implicated in primary cilium formation in epithelial cells, including the machinery best known for its involvement in establishing cell polarity and polarized membrane trafficking, is also discussed.     

Microhabitat selection in the sand recluse spider (Sicarius thomisoides): the effect of rock size and temperature

In spiders, temperature is considered an important environmental variable for microhabitat selection. In this study, we evaluated the effect of temperature and rock size on the presence of the sand recluse spider Sicarius thomisoides and the degree of selectivity in different locations. This species is a large spider that lives under rocks in desert and semi-desert climates and is particularly active during the summer. In Chile, these spiders can be found at both coastal and inland locations under different thermal conditions, where usually the temperatures are lower near the coast. If large-scale climatic conditions are important for this species, they may be expected to select lower rock temperatures on the coast than at inland locations. In addition, we would expect that the spiders would choose larger rocks in inland compared to coast locations, which reduce the effect of high temperatures. We found that the probability of finding individuals of this species increased according to rock temperature and rock size in the field. Our results suggest that S. thomisoides prefers larger and warmer rocks to shelter under during the day, this selectivity being similar at both coastal and inland locations. Thus, this species tends to select rocks with the same thermal and structural conditions, independent of the climatic conditions.     

Predation on eggs of Schneider’s dwarf caiman,Paleosuchus trigonatus (Schneider, 1807), by armadillos and other predators

Nests of Schneider’s dwarf caiman, Paleosuchus trigonatus, were located in the forests around three streams that drain into the Xingu River, Brazilian Amazonia, in October 2014. Camera traps were installed at the edge of four nests to document predators and female parental care. At two nests, females unsuccessfully defended their nests against one or more giant armadillos, Priodontes maximus, and nine-banded armadillos, Dasypus novemcinctus. Both armadillo species responded to the attack by fleeing and returning on the opposite side of the nest by going around the tree under which the nest was located. Giant armadillos have never before been recorded consuming caiman eggs and their diet has been described as consisting mostly of ants and termites. Another species of armadillo, Cabassous unicinctus, was also registered digging into a nest and probably consuming eggs, though it is generally considered to be primarily insectivorous. A tayra (Eira barbara), lizard (Tupinambis teguixin) and coati (Nasua nasua) were also registered taking eggs from nests during the day, but we obtained no registers of nest defence by caimans during the day. The three nests were attacked after 60 days of incubation, when the eggs were well developed.     

Liquid marbles.

The transport of a small amount of liquid on a solid is not a simple process, owing to the nature of the contact between the two phases. Setting a liquid droplet in motion requires non-negligible forces (because the contact-angle hysteresis generates a force opposing the motion), and often results in the deposition of liquid behind the drop. Different methods of levitation-electrostatic, electromagnetic, acoustic, or even simpler aerodynamic techniques-have been proposed to avoid this wetting problem, but all have proved to be rather cumbersome. Here we propose a simple alternative, which consists of encapsulating an aqueous liquid droplet with a hydrophobic powder. The resulting 'liquid marbles' are found to behave like a soft solid, and show dramatically reduced adhesion to a solid surface. As a result, motion can be generated using gravitational, electrical and magnetic fields. Moreover, because the viscous friction associated with motion is very small, we can achieve quick displacements of the droplets without any leaks. All of these features are of potential benefit in microfluidic applications, and also permit the study of a drop in a non-wetting situation-an issue of renewed interest following the recent achievement of super-hydrophobic substrates.     

On-chip natural assembly of silicon photonic bandgap crystals.

Photonic bandgap crystals can reflect light for any direction of propagation in specific wavelength ranges. This property, which can be used to confine, manipulate and guide photons, should allow the creation of all-optical integrated circuits. To achieve this goal, conventional semiconductor nanofabrication techniques have been adapted to make photonic crystals. A potentially simpler and cheaper approach for creating three-dimensional periodic structures is the natural assembly of colloidal microspheres. However, this approach yields irregular, polycrystalline photonic crystals that are difficult to incorporate into a device. More importantly, it leads to many structural defects that can destroy the photonic bandgap. Here we show that by assembling a thin layer of colloidal spheres on a silicon substrate, we can obtain planar, single-crystalline silicon photonic crystals that have defect densities sufficiently low that the bandgap survives. As expected from theory, we observe unity reflectance in two crystalline directions of our photonic crystals around a wavelength of 1.3 micrometres. We also show that additional fabrication steps, intentional doping and patterning, can be performed, so demonstrating the potential for specific device applications.     

Programmable and autonomous computing machine made of biomolecules.

Devices that convert information from one form into another according to a definite procedure are known as automata. One such hypothetical device is the universal Turing machine, which stimulated work leading to the development of modern computers. The Turing machine and its special cases, including finite automata, operate by scanning a data tape, whose striking analogy to information-encoding biopolymers inspired several designs for molecular DNA computers. Laboratory-scale computing using DNA and human-assisted protocols has been demonstrated, but the realization of computing devices operating autonomously on the molecular scale remains rare. Here we describe a programmable finite automaton comprising DNA and DNA-manipulating enzymes that solves computational problems autonomously. The automaton's hardware consists of a restriction nuclease and ligase, the software and input are encoded by double-stranded DNA, and programming amounts to choosing appropriate software molecules. Upon mixing solutions containing these components, the automaton processes the input molecule via a cascade of restriction, hybridization and ligation cycles, producing a detectable output molecule that encodes the automaton's final state, and thus the computational result. In our implementation 1012 automata sharing the same software run independently and in parallel on inputs (which could, in principle, be distinct) in 120 microl solution at room temperature at a combined rate of 109 transitions per second with a transition fidelity greater than 99.8%, consuming less than 10-10 W.     

Superconductivity in CaCuO2 as a result of field-effect doping.

Understanding the doping mechanisms in the simplest superconducting copper oxide-the infinite-layer compound ACuO2 (where A is an alkaline earth metal)-is an excellent way of investigating the pairing mechanism in high-transition-temperature (high-Tc) superconductors more generally. Gate-induced modulation of the carrier concentration to obtain superconductivity is a powerful means of achieving such understanding: it minimizes the effects of potential scattering by impurities, and of structural modifications arising from chemical dopants. Here we report the transport properties of thin films of the infinite-layer compound CaCuO2 using field-effect doping. At high hole- and electron-doping levels, superconductivity is induced in the nominally insulating material. Maximum values of Tc of 89 K and 34 K are observed respectively for hole- and electron-type doping of around 0.15 charge carriers per CuO2. We can explore the whole doping diagram of the CuO2 plane while changing only a single electric parameter, the gate voltage.     

Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo

In Parkinson's disease, brain dopamine neurons degenerate most prominently in the substantia nigra. Neurotrophic factors promote survival, differentiation and maintenance of neurons in developing and adult vertebrate nervous system. The most potent neurotrophic factor for dopamine neurons described so far is the glial-cell-line-derived neurotrophic factor (GDNF). Here we have identified a conserved dopamine neurotrophic factor (CDNF) as a trophic factor for dopamine neurons. CDNF, together with its previously described vertebrate and invertebrate homologue the mesencephalic-astrocyte-derived neurotrophic factor, is a secreted protein with eight conserved cysteine residues, predicting a unique protein fold and defining a new, evolutionarily conserved protein family. CDNF (Armetl1) is expressed in several tissues of mouse and human, including the mouse embryonic and postnatal brain. In vivo, CDNF prevented the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons in a rat experimental model of Parkinson's disease. A single injection of CDNF before 6-OHDA delivery into the striatum significantly reduced amphetamine-induced ipsilateral turning behaviour and almost completely rescued dopaminergic tyrosine-hydroxylase-positive cells in the substantia nigra. When administered four weeks after 6-OHDA, intrastriatal injection of CDNF was able to restore the dopaminergic function and prevent the degeneration of dopaminergic neurons in substantia nigra. Thus, CDNF was at least as efficient as GDNF in both experimental settings. Our results suggest that CDNF might be beneficial for the treatment of Parkinson's disease.