A myogenic differentiation checkpoint activated by genotoxic stress

Cell-cycle checkpoints help to protect the genomes of proliferating cells under genotoxic stress. In multicellular organisms, cell proliferation is often directed toward differentiation during development and throughout adult homeostasis. To prevent the formation of differentiated cells with genetic instability, we hypothesized that genotoxic stress may trigger a differentiation checkpoint. Here we show that exposure to genotoxic agents causes a reversible inhibition of myogenic differentiation. Muscle-specific gene expression is suppressed by DNA-damaging agents if applied prior to differentiation induction but not after the differentiation program is established. The myogenic determination factor, MyoD (encoded by Myod1), is a target of the differentiation checkpoint in myoblasts. The inhibition of MyoD by DNA damage requires a functional c-Abl tyrosine kinase (encoded by Abl1), but occurs in cells deficient for p53 (transformation-related protein 53, encoded by Trp53) or c-Jun (encoded by the oncogene Jun). These results support the idea that genotoxic stress can regulate differentiation, and identify a new biological function for DNA damage-activated signaling network.     

Delayed ageing through damage protection by the Arf/p53 pathway

The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity. Similar to cancer, ageing also results from the accumulation of damage and, therefore, we have reasoned that Arf/p53 could have anti-ageing activity by alleviating the load of age-associated damage. Here we show that genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity.     

Circular polarimetry reveals helical magnetic fields in the young stellar object HH 135-136

Magnetic fields are believed to have a vital role in regulating and shaping the flow of material onto and away from protostars during their initial mass accretion phase. It is becoming increasingly accepted that bipolar outflows are generated and collimated as material is driven along magnetic field lines and centrifugally accelerated off a rotating accretion disk. However, the precise role of the magnetic field is poorly understood and evidence for its shape and structure has not been forthcoming. Here we report imaging circular polarimetry in the near-infrared and Monte Carlo modelling showing that the magnetic field along the bipolar outflow of the HH 135-136 young stellar object is helical. The field retains this shape for large distances along the outflow, so the field structure can also provide the necessary magnetic pressure for collimation of the outflow. This result lends further weight to the hypothesis--central to any theory of star formation--that the outflow is an important instrument for the removal of high-angular-momentum material from the accretion disk, thereby allowing the central protostar to increase its mass.     

Mathematical,Philosophical and Semantic Considerations on Infinity (I): General Concepts

In the Reality we know, we cannot say if something is infinite whether we are doing Physics, Biology, Sociology or Economics. This means we have to be careful using this concept. Infinite structures do not exist in the physical world as far as we know. So what do mathematicians mean when they assert the existence of ω (the mathematical symbol for the set of all integers)? There is no universally accepted philosophy of mathematics but the most common belief is that mathematics touches on another worldly absolute truth. Many mathematicians believe that mathematics involves a special perception of an idealized world of absolute truth. This comes in part from the recognition that our knowledge of the physical world is imperfect and falls short of what we can apprehend with mathematical thinking. The objective of this paper is to present an epistemological rather than an historical vision of the mathematical concept of infinity that examines the dialectic between the actual and potential infinity.     

Extension of southern range and new specimens of the western gray squirrel, Sciurus griseus anthonyi (Mammalia: Sciuridae), in Baja California, México

We documented a southern range extension and new specimens of western gray squirrel ( Sciurus griseus anthonyi ) for the state of Baja California, México. The most recent specimen was collected in the town Cataviña and represents the southernmost record for the species and subspecies. Repeated observations of individuals in this new location suggest the presence of a marginal population in Mediterranean chaparral–desert scrub transition vegetation. Documentamos la extension de ámbito más sureño y nuevos especímenes de a ardilla gris occidental ( Sciurus griseus anthonyi ) para el Estado de Baja California, México. El espécimen más reciente fue recolectado en el poblado de Cataviña y representa el registro más sureño para la especie y subespecie. Observaciones repetidas de individuos en esta última localidad sureña sugiere la presencia de una población marginal en vegetación de transición de chaparral mediterráneo–matorral desértico.     

Fluorescence spectroscopy and molecular dynamics simulations in studies on the mechanism of membrane destabilization by antimicrobial peptides

Since their initial discovery, 30 years ago, antimicrobial peptides (AMPs) have been intensely investigated as a possible solution to the increasing problem of drug-resistant bacteria. The interaction of antimicrobial peptides with the cellular membrane of bacteria is the key step of their mechanism of action. Fluorescence spectroscopy can provide several structural details on peptide–membrane systems, such as partition free energy, aggregation state, peptide position and orientation in the bilayer, and the effects of the peptides on the membrane order. However, these “low-resolution” structural data are hardly sufficient to define the structural requirements for the pore formation process. Molecular dynamics simulations, on the other hand, provide atomic-level information on the structure and dynamics of the peptide–membrane system, but they need to be validated experimentally. In this review we summarize the information that can be obtained by both approaches, highlighting their versatility and complementarity, suggesting that their synergistic application could lead to a new level of insight into the mechanism of membrane destabilization by AMPs.     

Membrane-shed vesicles from the parasite <Emphasis Type="Italic">Trichomonas vaginalis</Emphasis>: characterization and their association with cell interaction

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract, where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Despite the serious consequences associated with trichomoniasis disease, little is known about parasite or host factors involved in attachment of the parasite-to-host epithelial cells. Here, we report the identification of microvesicle-like structures (MVs) released by T. vaginalis. MVs are considered universal transport vehicles for intercellular communication as they can incorporate peptides, proteins, lipids, miRNA, and mRNA, all of which can be transferred to target cells through receptor–ligand interactions, fusion with the cell membrane, and delivery of a functional cargo to the cytoplasm of the target cell. In the present study, we demonstrated that T. vaginalis release MVs from the plasma and the flagellar membranes of the parasite. We performed proteomic profiling of these structures demonstrating that they possess physical characteristics similar to mammalian extracellular vesicles and might be selectively charged with specific protein content. In addition, we demonstrated that viable T. vaginalis parasites release large vesicles (LVs), membrane structures larger than 1 µm that are able to interact with other parasites and with the host cell. Finally, we show that both populations of vesicles present on the surface of T vaginalis are induced in the presence of host cells, consistent with a role in modulating cell interactions.