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.     

Chromatin-remodeling complex specificity and embryonic vascular development

Vascular development is a dynamic process that relies on the coordinated expression of numerous genes, but the factors that regulate gene expression during blood vessel development are not well defined. ATP-dependent chromatin-remodeling complexes are gaining attention for their specific temporal and spatial effects on gene expression during vascular development. Genetic mutations in chromatin-remodeling complex subunits are revealing roles for the complexes in vascular signaling pathways at discrete developmental time points. Phenotypic analysis of these models at various stages of vascular development will continue to expand our understanding of how chromatin remodeling impacts new blood vessel growth. Such research could also provide novel therapeutic targets for the treatment of vascular pathologies.     

Infection of young Douglas-firs by dwarf mistletoe in the Southwest

Studies in several areas in Arizona and New Mexico show that dwarf mistletoe ( Arceuthobium douglasii ) is rare in young Douglas-firs growing under infected overstories. Less than 5% of the Douglas-firs under 26 years old and less than 6% of those under 1.4m tall were infected in 77 mistletoe-infested stands. Both percent infection and mean dwarf mistletoe rating of young Douglas-firs increased as tree age, height, and stand dwarf mistletoe ratings increased.     

Giant magneto resistance and temperature coefficient of resistance in Sm0.55Sr0.30Ag0.15MnO3 perovskite

Silver ions substituted samarium strontium manganite (Sm0.55Sr0.30Ag0.15MnO3) pervoskite was synthesized by using respective oxides in stoichiometric ratio through solid state reaction. The as-prepared sample was characterized by various analytical techniques to confirm its formation and understand the effect of monovalent silver ions in pervoskite lattice. X-ray diffraction pattern confirms the single phase formation while grain morphology in SEM image indicates good connectivity among the grains. The enhancement in metal to insulator transition temperature shows quenched disorder and magnetoresistance phenomena. The magnetoresistance (MR) and temperature coefficient of resistance (TCR) emerge from grain growth factor and homogeneity induced by Ag+ ions in the lattice. The reduction in hysteresis loss resulted from antiferromagnetic - ferromagnetic (TN) and ferromagnetic - paramagnetic (Tc) transitions reveals the removal of disorder in perovskite lattice by Ag+ ions substitution. This increases the magnetic moment across distinct ions on the applying magnetic field. The rise in MR% (~99%) with silver doping emerging from smooth spin tunneling of the grains across the boundary and suppression of the disordered magnetic fluctuations with increase in magnetic field has been reported. The present compound exhibits the first order nature of magnetism and observed first time the highest value of TCR ~ 95%.     

假高粱、黑高梁和高粱细胞学指标比较及其生态学意义

假高粱(Sorghum halepense(L.)Pers.)是世界十大恶性杂草之一.黑高粱(S.almum Parodi)和高粱(S.bicolor(L.)Moench)是假高粱的两种近缘种,其中黑高粱有入侵性,高粱则为栽培植物,不表现出入侵性.为了解影响植物入侵能力的生物学因素,比较了高粱属3种植物根尖分生组织细胞的染色体、细胞核、细胞大小和细胞有丝分裂指数.结果表明,高粱染色体平均投影面积最大,其次是黑高粱,假高粱的最小;就细胞和细胞核大小而言,都是高粱最大、其次是黑高粱和假高粱;在25~35℃的温度范围内,高粱根尖分生区细胞的有丝分裂速率最低,假高粱的最高.3种植物的种子(颖果)以高粱最大,黑高粱和假高粱的显著小,幼苗相对生长速率以高粱最小,假高粱的最高.3种植物的细胞分裂速率与其染色体、细胞核、细胞和种子大小存在显著相关,表明入侵性植物往往具有较小的分生组织细胞、细胞核和种子,但是有相对高的细胞分裂速率和幼苗相对干重.因此,根尖分生组织细胞学指标在高粱属植物入侵能力评估上有潜在应用价值.     

Expanding the diversity of chemical protein modification allows post-translational mimicry

One of the most important current scientific paradoxes is the economy with which nature uses genes. In all higher animals studied, we have found many fewer genes than we would have previously expected. The functional outputs of the eventual products of genes seem to be far more complex than the more restricted blueprint. In higher organisms, the functions of many proteins are modulated by post-translational modifications (PTMs). These alterations of amino-acid side chains lead to higher structural and functional protein diversity and are, therefore, a leading contender for an explanation for this seeming incongruity. Natural protein production methods typically produce PTM mixtures within which function is difficult to dissect or control. Until now it has not been possible to access pure mimics of complex PTMs. Here we report a chemical tagging approach that enables the attachment of multiple modifications to bacterially expressed (bare) protein scaffolds: this approach allows reconstitution of functionally effective mimics of higher organism PTMs. By attaching appropriate modifications at suitable distances in the widely-used LacZ reporter enzyme scaffold, we created protein probes that included sensitive systems for detection of mammalian brain inflammation and disease. Through target synthesis of the desired modification, chemistry provides a structural precision and an ability to retool with a chosen PTM in a manner not available to other approaches. In this way, combining chemical control of PTM with readily available protein scaffolds provides a systematic platform for creating probes of protein-PTM interactions. We therefore anticipate that this ability to build model systems will allow some of this gene product complexity to be dissected, with the aim of eventually being able to completely duplicate the patterns of a particular protein's PTMs from an in vivo assay into an in vitro system.     

Discovery of 40Mg and 42Al suggests neutron drip-line slant towards heavier isotopes

A fundamental question in nuclear physics is what combinations of neutrons and protons can make up a nucleus. Many hundreds of exotic neutron-rich isotopes have never been observed; the limit of how many neutrons a given number of protons can bind is unknown for all but the lightest elements, owing to the delicate interplay between single particle and collective quantum effects in the nucleus. This limit, known as the neutron drip line, provides a benchmark for models of the atomic nucleus. Here we report a significant advance in the determination of this limit: the discovery of two new neutron-rich isotopes--40Mg and 42Al--that are predicted to be drip-line nuclei. In the past, several attempts to observe 40Mg were unsuccessful; moreover, the observation of 42Al provides an experimental indication that the neutron drip line may be located further towards heavier isotopes in this mass region than is currently believed. In stable nuclei, attractive pairing forces enhance the stability of isotopes with even numbers of protons and neutrons. In contrast, the present work shows that nuclei at the drip line gain stability from an unpaired proton, which narrows the shell gaps and provides the opportunity to bind many more neutrons.