Gravity constraint in cell phenotypic determination

Distinct phenotypes emerge spontaneously when mammalian cells are cultured under microgravity conditions. Such finding is explained by the interplay among the intrinsic stochasticity, which, in turn, is successively ‘canalized’ and sustained by the activation of a specific gene regulatory network. However, when the two cell subsets are reseeded into a normal gravity field the two phenotypes collapse into one. Gravity constraints the system in adopting only one phenotype. Cell fate commitment is achieved through a de novo reshaping of the overall cell morphological and functional organization, and cannot be explained as a ‘selecting’ effect. Those findings highlight how constraints – acting as global order factors – drive cell specification and behavior. These data cast on doubt the current explanatory bottom-up, molecular based models

Journey to Mars. A Biomedical Challenge. Perspective on future human space flight

Manned space flight has been the greatest human and technological adventure of the past half-century. Putting people into places and situations unprecedented in history is stirred the imagination while the human experience was expanding and redefining. Yet, space exploration compels humans to confront a hostile environment of cosmic radiations, radical changes in the gravity and magnetic fields, as well as social isolation. Therefore, any space traveller is submitted to relevant health-related threats. In the twenty-first century, human space flight is poised to continue, but it will enjoy the ongoing developments in science and technology. It will become more networked, more global, and more oriented toward primary goals. A novel international human space flight policy could help achieve these objectives by clarifying the rationale, the ethics of acceptable risk, the role of remote presence, and the need for balance between funding and ambition to justify the risk of human lives. In order to address such a challenge, a preliminary careful survey of the available scientific data is mandatory to set forth adequate countermeasures. Envisaged solutions should provide a sound and technically feasible approach for counteracting microgravity and cosmic rays effects, which represent the main health risk for space crews. This objective must necessarily be sustained by national/international space agencies, which would coordinate their common efforts into a defined international spaceflight program

Using the full IASI spectrum for the physical retrieval of temperature, H2O, HDO, O3, minor and trace gases

IASI (Infrared Atmospheric Sounder Interferometer) is flying on the European MetOp series of weather satellites. Besides acquiring temperature and humidity data, IASI also observes the infrared emission of the main minor and trace atmospheric components with high precision. The retrieval of these gases would be highly beneficial to the efforts of scientists monitoring Earths climate. IASI retrieval capability and algorithms have been mostly driven by Numerical Weather Prediction centers, whose limited resources for data transmission and computing is hampering the full exploitation of IASI information content. The quest for real or nearly real time processing has affected the precision of the estimation of minor and trace gases, which are normally retrieved on a very coarse spatial grid. The paper presents the very first retrieval of the complete suite of IASI target parameters by exploiting all its 8461 channels. The analysis has been exemplified for sea surface and the target parameters will include sea surface temperature, temperature profile, water vapour and HDO profiles, ozone profile, total column amount of CO, CO2, CH4, N2O, SO2, HNO3, NH3, OCS and CF4. Concerning CO2, CH4 and N2O, it will be shown that their colum amount can be obtained for each single IASI IFOV (Instantaneous Field of View) with a precision better than 1-2%, which opens the possibility to analyze, e.g., the formation of regional patterns of greenhouse gases. To assess the quality of the retrieval, a case study has been set up which considers two years of IASI soundings over the Hawaii, Manua Loa validation station

KALMAN FILTER RETRIEVAL OF SEA SKIN TEMPERATURE FROM SEVIRI: A COMPARISON CASE STUDY

The high temporal resolution of data acquisition by geostationary satellites and their capability to resolve the diurnal cycle allow for the retrieval of a valuable source of information about geophysical parameters. To exploit this information we have developed a Kalman filter methodology for the retrieval of surface emissivity and temperature from radiance measurements made from geostationary platforms. The application of the retrieval methodology to SEVIRI (Spinning Enhanced Visible and Infrared Imager) infrared channels shows that we can simultaneously retrieve surface emissivity and temperature with an accuracy of ± 0.005 and ± 0.2 K, respectively. This performance is exemplified in this paper with a case study, which considers the retrieval of sea skin temperature for a target area of the Naples Gulf. Retrieval for temperature has been intercompared with similar products derived from AVHRR (Advanced Very High Resolution Radiometer) and MODIS (Moderate Resolution Imaging Spectroradiometer) satellite sensors

Hyper fast radiative transfer for the physical retrieval of surface parameters from SEVIRI observations

This paper describes the theoretical aspects of a fast scheme for the physical retrieval of surface temperature and emissivity from SEVIRI data, their implementation and some sample results obtained. The scheme is based on a Kalman Filter approach, which effectively exploits the temporal continuity in the observations of the geostationary Meteosat Second Generation (MSG) platform, on which SEVIRI (Spinning Enhanced Visible and InfraRed Imager) operates. Such scheme embodies in its core a physical retrieval algorithm, which employs an hyper fast radiative transfer code highly customized for this retrieval task. Radiative transfer and its customizations are described in detail. Fastness, accuracy and stability of the code are fully documented for a variety of surface features, showing a peculiar application to the massive Greek forest fires in August 2007

Simulated microgravity triggers epithelial mesenchymal transition in human keratinocytes

The microgravitational environment is known to affect the cellular behaviour inducing modulation of gene expression and enzymatic activities, epigenetic modifications and alterations of the structural organization. Simulated microgravity, obtained in the laboratory setting through the use of a Random Positioning Machine (RPM), represents a well recognized and useful tool for the experimental studies of the cellular adaptations and molecular changes in response to weightlessness. Short exposure of cultured human keratinocytes to the RPM microgravity influences the cellular circadian clock oscillation. Therefore, here we searched for changes on the regenerative ability and response to tissue damage of human epidermal cells through the analysis of the effects of the simulated microgravity on the re-epithelialization phase of the repair and wound healing process. Combining morphological, biochemical and molecular approaches, we found that the simulated microgravity exposure of human keratinocytes promotes a migratory behavior and triggers the epithelial-mesenchymal transition (EMT) through expression of the typical EMT transcription factors and markers, such as Snail1, Snail2 and ZEB2, metalloproteases, mesenchymal adhesion molecules and cytoskeletal components

Effects of simulated microgravity In vitro on human metaphase II oocytes: an electron microscopy-based study

The Gravity Force to which living beings are subjected on Earth rules the functionality of most biological processes in many tissues. It has been reported that a situation of Microgravity (such as that occurring in space) causes negative effects on living beings. Astronauts returning from space shuttle missions or from the International Space Station have been diagnosed with various health problems, such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and vestibular and sensory imbalance, including impaired visual acuity, altered metabolic and nutritional status, and immune system dysregulation. Microgravity has profound effects also on reproductive functions. Female astronauts, in fact, suppress their cycles during space travels, and effects at the cellular level in the early embryo development and on female gamete maturation have also been observed. The opportunities to use space flights to study the effects of gravity variations are limited because of the high costs and lack of repeatability of the experiments. For these reasons, the use of microgravity simulators for studying, at the cellular level, the effects, such as those, obtained during/after a spatial trip, are developed to confirm that these models can be used in the study of body responses under conditions different from those found in a unitary Gravity environment (1 g). In view of this, this study aimed to investigate in vitro the effects of simulated microgravity on the ultrastructural features of human metaphase II oocytes using a Random Positioning Machine (RPM). We demonstrated for the first time, by Transmission Electron Microscopy analysis, that microgravity might compromise oocyte quality by affecting not only the localization of mitochondria and cortical granules due to a possible alteration of the cytoskeleton but also the function of mitochondria and endoplasmic reticulum since in RPM oocytes we observed a switch in the morphology of smooth endoplasmic reticulum (SER) and associated mitochondria from mitochondria-SER aggregates to mitochondria–vesicle complexes. We concluded that microgravity might negatively affect oocyte quality by interfering in vitro with the normal sequence of morphodynamic events essential for acquiring and maintaining a proper competence to fertilization in human oocyte

Inositol induces mesenchymal-epithelial reversion in breast cancer cells through cytoskeleton rearrangement

Inositol displays multi-targeted effects on many biochemical pathways involved in epithelial-mesenchymal transition (EMT). As Akt activation is inhibited by inositol, we investigated if such effect could hamper EMT in MDA-MB-231 breast cancer cells. In cancer cells treated with pharmacological doses of inositol E-cadherin was increased, β-catenin was redistributed behind cell membrane, and metalloproteinase-9 was significantly reduced, while motility and invading capacity were severely inhibited. Those changes were associated with a significant down-regulation of PI3K/Akt activity, leading to a decrease in downstream signaling effectors: NF-kB, COX-2, and SNAI1. Inositol-mediated inhibition of PS1 leads to lowered Notch 1 release, thus contributing in decreasing SNAI1 levels. Overall, these data indicated that inositol inhibits the principal molecular pathway supporting EMT. Similar results were obtained in ZR-75, a highly metastatic breast cancer line. These findings are coupled with significant changes on cytoskeleton. Inositol slowed-down vimentin expression in cells placed behind the wound-healing edge and stabilized cortical F-actin. Moreover, lamellipodia and filopodia, two specific membrane extensions enabling cell migration and invasiveness, were no longer detectable after inositol addiction. Additionally, fascin and cofilin, two mandatory required components for F-actin assembling within cell protrusions, were highly reduced. These data suggest that inositol may induce an EMT reversion in breast cancer cells, suppressing motility and invasiveness through cytoskeleton modifications

Gravity constraints drive biological systems toward specific organization patterns. Commitment of cell specification is constrained by physical cues

Different cell lineages growing in microgravity undergo a spontaneous transition leading to the emergence of two distinct phenotypes. By returning these populations in a normal gravitational field, the two phenotypes collapse, recovering their original configuration. In this review, we hypothesize that, once the gravitational constraint is removed, the system freely explores its phenotypic space, while, when in a gravitational field, cells are “constrained” to adopt only one favored configuration. We suggest that the genome allows for a wide range of “possibilities” but it is unable per se to choose among them: the emergence of a specific phenotype is enabled by physical constraints that drive the system toward a preferred solution. These findings may help in understanding how cells and tissues behave in both development and cancer

Physical constraints in cell fate specification. A case in point. Microgravity and phenotypes differentiation

Data obtained by studying mammalian cells in absence of gravity strongly support the notion that cell fate specification cannot be understood according to the current molecular model. A paradigmatic case in point is provided by studying cell populations growing in absence of gravity. When the physical constraint (gravity) is ‘experimentally removed’, cells spontaneously allocate into two morphologically different phenotypes. Such phenomenon is likely enacted by the intrinsic stochasticity, which, in turn, is successively ‘canalized’ by a specific gene regulatory network. Both phenotypes are thermodynamically and functionally ‘compatibles’ with the new, modified environment. However, when the two cell subsets are reseeded into the 1g gravity field the two phenotypes collapse into one. Gravity constraints the system in adopting only one phenotype, not by selecting a pre-existing configuration, but more precisely shaping it de-novo through the modification of the cytoskeleton three-dimensional structure. Overall, those findings highlight how macro-scale features are irreducible to lower-scale explanations. The identification of macroscale control parameters e as those depending on the field (gravity, electromagnetic fields) or emerging from the cooperativity among the field's components (tissue stiffness, cellto- cell connectivity) e are mandatory for assessing boundary conditions for models at lower scales, thus providing a concrete instantiation of top-down effects