The FHIT gene product: tumor suppressor and genome “caretaker”

The FHIT gene at FRA3B is one of the earliest and most frequently altered genes in the majority of human cancers. It was recently discovered that the FHIT gene is not the most fragile locus in epithelial cells, the cell of origin for most Fhit-negative cancers, eroding support for past claims that deletions at this locus are simply passenger events that are carried along in expanding cancer clones, due to extreme vulnerability to DNA damage rather than to loss of FHIT function. Indeed, recent reports have reconfirmed FHIT as a tumor suppressor gene with roles in apoptosis and prevention of the epithelial–mesenchymal transition. Other recent works have identified a novel role for the FHIT gene product, Fhit, as a genome “caretaker.” Loss of this caretaker function leads to nucleotide imbalance, spontaneous replication stress, and DNA breaks. Because Fhit loss-induced DNA damage is “checkpoint blind,” cells accumulate further DNA damage during subsequent cell cycles, accruing global genome instability that could facilitate oncogenic mutation acquisition and expedite clonal expansion. Loss of Fhit activity therefore induces a mutator phenotype. Evidence for FHIT as a mutator gene is discussed in light of these recent investigations of Fhit loss and subsequent genome instability.     

Reproductive ecology of the glass frog Espadarana prosoblepon (Anura: Centrolenidae) in an urban forest of the Central Andes of Colombia

Population and reproductive behaviour aspects of the glass frog Espadarana prosoblepon are well known for populations from Central America, but similar information is lacking for populations from South America. We recorded the reproductive ecology of a population of the glass frog E. prosoblepon in the city of Armenia, Central Andes of Colombia. With weekly surveys with mark-recapture between December 2013 and November 2015, we monitored activity patterns and evaluated if the probability of males mating is associated to their body size or to chorus tenure (i.e. the number of nights a same individual is calling for attracting a mate). In addition, upon observing an amplexus, we recorded the behaviour of the individuals until oviposition and noted characteristics of egg clutch. We recorded 47 males and 32 females, nine amplexus events, eight ovipositions, and 21 egg clutches (35.4 ± 4.79 eggs per clutch, N = 29). Activity of males and females and the number of egg clutches were positively correlated to rainfall. Mating success of males was not associated to their body size, but it was positively associated to longer chorus tenure; clutches from large females had a higher number of eggs than clutches from small females. Oviposition occurred on average 3.76 ± 1.74 hours after we first observed the amplexus, occurring 93.1% of the time in fronds of Selaginella geniculata at an average height of 1.58 ± 0.44 m. After the oviposition, the male left the site, while the female remained between 30 and 45 min, partially covering the eggs. The reproductive behaviour of E. prosoblepon did not vary widely between a population in Costa Rica and our population in time to oviposition, and mating success of males associated to chorus tenure; however, in our study population we recorded a larger clutch size and the preference for S. geniculata fronds as oviposition substrate.     

Eustigmaeus floridensis sp. nov., a new mite species of the genus Eustigmaeus Berlese, 1910 (Acari: Stigmaeidae) from citrus in Florida

Eustigmaeus floridensis sp. nov. is described and illustrated based on female specimens collected from citrus trees in Florida, USA. The new species is closely related to Eustigmaeus arcuata, Eustigmaeus segnis and Eustigmaeus microsegnis, all known to occur in Florida. Eustigmaeus floridensis sp. nov. can be distinguished by larger dimples associated with setae sce, d₂ and e₁ containing at least four or more vacuoles centrally; dorsal body setae broadly lanceolate and feather-like, except c₂, which is slender; anogenital area with striae and one pair of serrated aggenital (ag1) and three pairs of serrated pseudanal (ps_1?3) setae. A key to the Eustigmaeus species known to occur across USA is also provided.     

Phospholipid flippases attenuate LPS-induced TLR4 signaling by mediating endocytic retrieval of Toll-like receptor 4

P4-ATPases are lipid flippases that catalyze the transport of phospholipids to create membrane phospholipid asymmetry and to initiate the biogenesis of transport vesicles. Here we show, for the first time, that lipid flippases are essential to dampen the inflammatory response and to mediate the endotoxin-induced endocytic retrieval of Toll-like receptor 4 (TLR4) in human macrophages. Depletion of CDC50A, the β-subunit that is crucial for the activity of multiple P4-ATPases, resulted in endotoxin-induced hypersecretion of proinflammatory cytokines, enhanced MAP kinase signaling and constitutive NF-κB activation. In addition, CDC50A-depleted THP-1 macrophages displayed reduced tolerance to endotoxin. Moreover, endotoxin-induced internalization of TLR4 was strongly reduced and coincided with impaired endosomal MyD88-independent signaling. The phenotype of CDC50A-depleted cells was also induced by separate knockdown of two P4-ATPases, namely ATP8B1 and ATP11A. We conclude that lipid flippases are novel elements of the innate immune response that are essential to attenuate the inflammatory response, possibly by mediating endotoxin-induced internalization of TLR4.     

Electric charge in hyperbolic motion: the early history

The study of an electric charge in hyperbolic motion is an important aspect of Minkowski’s geometrical formulation of electrodynamics. In “Space and Time”, his last publication before his premature death, Minkowski gives a brief geometrical recipe for calculating the four-force with which an electric charge acts on another electric charge. The subsequent work of Born, Sommerfeld, Laue, and Pauli filled in the missing derivation details. Here, we bring together these early contributions, in an effort to provide a more modern, accessible, and unified exposition of the early history of the electric charge in hyperbolic motion.

     

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.     

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.     

ARFIMA approximation and forecasting of the limiting aggregate structure of long‐memory process

This article studies Man and Tiao's (2006) low‐order autoregressive fractionally integrated moving‐average (ARFIMA) approximation to Tsai and Chan's (2005b) limiting aggregate structure of the long‐memory process. In matching the autocorrelations, we demonstrate that the approximation works well, especially for larger d values. In computing autocorrelations over long lags for larger d value, using the exact formula one might encounter numerical problems. The use of the ARFIMA(0, d, d?₁) model provides a useful alternative to compute the autocorrelations as a really close approximation. In forecasting future aggregates, we demonstrate the close performance of using the ARFIMA(0, d, d?₁) model and the exact aggregate structure. In practice, this provides a justification for the use of a low‐order ARFIMA model in predicting future aggregates of long‐memory process. Copyright © 2008 John Wiley & Sons, Ltd.