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.     

New insights on the external features of egg capsules and embryo development in the squid Loligo vulgaris

The embryonic development of the squid Loligo vulgaris was observed from 183 egg masses collected from special devices deployed throughout Cabrera National Park (Baleares Islands, western Mediterranean Sea). Sequence alignment analysis of the cytochrome oxidase I gene revealed that all embryos belonged to L. vulgaris. In total, 549 egg capsules were examined. Viable egg capsules (n = 420) were classified into one of five maturation stages according to the primary external features. The length of the viable egg capsules varied between 40 and 170 mm, and increased with embryonic development. The non-viable capsules (n = 129) were categorized into four groups: I (Ginger root), non-viable II and III, and empty egg capsule (IV). The percentage of non-viable capsules (i.e. grades I, II and III) was 92.25%. Empty capsules accounted for 7.75% of the total non-viable egg capsules. Embryonic development was classified into a second scale of eight stages. Egg capsule stage and embryonic stage were significantly related (n = 420; p < 0.001), facilitating the determination of the embryo developmental phase based on the outward appearance of the egg capsules. The embryo development stage based on the external features of the egg capsules might constitute an innovative tool for in situ embryological data collection. This new method is neither time consuming nor invasive, and could be helpful in fishing cruises, for scuba diving visual census in natural habitats and for laboratory culture. Slight variability in the developmental embryonic stages within egg capsules from the same egg mass was identified. The origin of this asynchrony is discussed. Chronological appearance of organs was similar to that of the six loliginid species previously examined. However, some developmental changes in the timing or rate of events (heterochronies) were observed: Hoyle’s organ was formed earlier in L. vulgaris and the appearance of ventral chromatophores was slightly delayed (2 days) compared with the other species considered.     

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.     

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.     

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.     

South-polar features on Venus similar to those near the north pole

Venus has no seasons, slow rotation and a very massive atmosphere, which is mainly carbon dioxide with clouds primarily of sulphuric acid droplets. Infrared observations by previous missions to Venus revealed a bright 'dipole' feature surrounded by a cold 'collar' at its north pole. The polar dipole is a 'double-eye' feature at the centre of a vast vortex that rotates around the pole, and is possibly associated with rapid downwelling. The polar cold collar is a wide, shallow river of cold air that circulates around the polar vortex. One outstanding question has been whether the global circulation was symmetric, such that a dipole feature existed at the south pole. Here we report observations of Venus' south-polar region, where we have seen clouds with morphology much like those around the north pole, but rotating somewhat faster than the northern dipole. The vortex may extend down to the lower cloud layers that lie at about 50 km height and perhaps deeper. The spectroscopic properties of the clouds around the south pole are compatible with a sulphuric acid composition.