127 research outputs found
VenSAR on EnVision: taking Earth Observation radar to Venus
Venus should be the most Earth-like of all our planetary neighbours: its size, bulk composition and distance from the Sun are very similar to those of Earth. How and why did it all go wrong for Venus? What lessons can be learned about the life story of terrestrial planets in general, in this era of discovery of Earth-like exoplanets? Were the radically different evolutionary paths of Earth and Venus driven solely by distance from the Sun, or do internal dynamics, geological activity, volcanic outgassing and weathering also play an important part? EnVision is a proposed ESA Medium class mission designed to take Earth Observation technology to Venus to measure its current rate of geological activity, determine its geological history, and the origin and maintenance of its hostile atmosphere, to understand how Venus and Earth could have evolved so differently. EnVision will carry three instruments: the Venus Emission Mapper (VEM); the Subsurface Radar Sounder (SRS); and VenSAR, a world-leading European phased array synthetic aperture radar that is the subject of this article. VenSAR will obtain images at a range of spatial resolutions from 30 m regional coverage to 1 m images of selected areas; an improvement of two orders of magnitude on Magellan images; measure topography at 15 m resolution vertical and 60 m spatially from stereo and InSAR data; detect cm-scale change through differential InSAR, to characterise volcanic and tectonic activity, and estimate rates of weathering and surface alteration; and characterise of surface mechanical properties and weathering through multi-polar radar data. These data will be directly comparable with Earth Observation radar data, giving geoscientists unique access to an Earth-sized planet that has evolved on a radically different path to our own, offering new insights on the Earth-sized exoplanets across the galaxy
Haploinsufficiency for p190B RhoGAP inhibits MMTV-Neu tumor progression
Introduction: Rho signaling regulates key cellular processes including proliferation, survival, and migration, and it has been implicated in the development of many types of cancer including breast cancer. P190B Rho GTPase activating protein (RhoGAP) functions as a major inhibitor of the Rho GTPases. P190B is required for mammary gland morphogenesis, and overexpression of p190B in the mammary gland induces hyperplastic lesions. Hence, we hypothesized that p190B may play a pivotal role in mammary tumorigenesis. Methods: To investigate the effects of loss of p190B function on mammary tumor progression, p190B heterozygous mice were crossed with an MMTV-Neu breast cancer model. Effects of p190B deficiency on tumor latency, multiplicity, growth, preneoplastic progression and metastasis were evaluated. To investigate potential differences in tumor angiogenesis between the two groups, immunohistochemistry to detect von Willebrand factor was performed and quantified. To examine gene expression of potential mediators of the angiogenic switch, an angiogenesis PCR array was utilized and results were confirmed using immunohistochemistry. Finally, reciprocal transplantation of tumor fragments was performed to determine the impact of stromal deficiency of p190B on tumor angiogenesis. Results: P190B deficiency reduced tumor penetrance (53% of mice vs. 100% of mice formed tumors) and markedly delayed tumor onset by an average of 46 weeks. Tumor multiplicity was also decreased, but an increase in the number of preneoplastic lesions was detected indicating that p190B deficiency inhibited preneoplastic progression. Angiogenesis was decreased in the p190B heterozygous tumors, and expression of a potent angiogenic inhibitor, thrombospondin-1, was elevated in mammary glands. Transplantation of tumor fragments into wild-type recipients restored tumor angiogenesis. Strikingly, tumor fragments were unable to grow when transplanted into recipients. Conclusions: These data suggest that p190B haploinsufficiency in the epithelium inhibits MMTV-Neu tumor initiation. Furthermore, p190B deficiency in the vasculature is responsible, in part, for the inhibition of MMTV-Neu tumor progression
Revised Lithostratigraphy of the Sonsela Member (Chinle Formation, Upper Triassic) in the Southern Part of Petrified Forest National Park, Arizona
BACKGROUND: Recent revisions to the Sonsela Member of the Chinle Formation in Petrified Forest National Park have presented a three-part lithostratigraphic model based on unconventional correlations of sandstone beds. As a vertebrate faunal transition is recorded within this stratigraphic interval, these correlations, and the purported existence of a depositional hiatus (the Tr-4 unconformity) at about the same level, must be carefully re-examined. METHODOLOGY/PRINCIPAL FINDINGS: Our investigations demonstrate the neglected necessity of walking out contacts and mapping when constructing lithostratigraphic models, and providing UTM coordinates and labeled photographs for all measured sections. We correct correlation errors within the Sonsela Member, demonstrate that there are multiple Flattops One sandstones, all of which are higher than the traditional Sonsela sandstone bed, that the Sonsela sandstone bed and Rainbow Forest Bed are equivalent, that the Rainbow Forest Bed is higher than the sandstones at the base of Blue Mesa and Agate Mesa, that strata formerly assigned to the Jim Camp Wash beds occur at two stratigraphic levels, and that there are multiple persistent silcrete horizons within the Sonsela Member. CONCLUSIONS/SIGNIFICANCE: We present a revised five-part model for the Sonsela Member. The units from lowest to highest are: the Camp Butte beds, Lot's Wife beds, Jasper Forest bed (the Sonsela sandstone)/Rainbow Forest Bed, Jim Camp Wash beds, and Martha's Butte beds (including the Flattops One sandstones). Although there are numerous degradational/aggradational cycles within the Chinle Formation, a single unconformable horizon within or at the base of the Sonsela Member that can be traced across the entire western United States (the "Tr-4 unconformity") probably does not exist. The shift from relatively humid and poorly-drained to arid and well-drained climatic conditions began during deposition of the Sonsela Member (low in the Jim Camp Wash beds), well after the Carnian-Norian transition
The genetic basis and evolution of red blood cell sickling in deer
Crescent-shaped red blood cells, the hallmark of sickle-cell disease, present a striking departure from the biconcave disc shape normally found in mammals. Characterized by increased mechanical fragility, sickled cells promote haemolytic anaemia and vaso-occlusions and contribute directly to disease in humans. Remarkably, a similar sickle-shaped morphology has been observed in erythrocytes from several deer species, without obvious pathological consequences. The genetic basis of erythrocyte sickling in deer, however, remains unknown. Here, we determine the sequences of human β-globin orthologues in 15 deer species and use protein structural modelling to identify a sickling mechanism distinct from the human disease, coordinated by a derived valine (E22V) that is unique to sickling deer. Evidence for long-term maintenance of a trans-species sickling/non-sickling polymorphism suggests that sickling in deer is adaptive. Our results have implications for understanding the ecological regimes and molecular architectures that have promoted convergent evolution of sickling erythrocytes across vertebrates
NO2 inhalation induces maturation of pulmonary CD11c+ cells that promote antigenspecific CD4+ T cell polarization
<p>Abstract</p> <p>Background</p> <p>Nitrogen dioxide (NO<sub>2</sub>) is an air pollutant associated with poor respiratory health, asthma exacerbation, and an increased likelihood of inhalational allergies. NO<sub>2 </sub>is also produced endogenously in the lung during acute inflammatory responses. NO<sub>2 </sub>can function as an adjuvant, allowing for allergic sensitization to an innocuous inhaled antigen and the generation of an antigen-specific Th2 immune response manifesting in an allergic asthma phenotype. As CD11c<sup>+ </sup>antigen presenting cells are considered critical for naïve T cell activation, we investigated the role of CD11c<sup>+ </sup>cells in NO<sub>2</sub>-promoted allergic sensitization.</p> <p>Methods</p> <p>We systemically depleted CD11c<sup>+ </sup>cells from transgenic mice expressing a simian diphtheria toxin (DT) receptor under of control of the CD11c promoter by administration of DT. Mice were then exposed to 15 ppm NO<sub>2 </sub>followed by aerosolized ovalbumin to promote allergic sensitization to ovalbumin and were studied after subsequent inhaled ovalbumin challenges for manifestation of allergic airway disease. In addition, pulmonary CD11c<sup>+ </sup>cells from wildtype mice were studied after exposure to NO<sub>2 </sub>and ovalbumin for cellular phenotype by flow cytometry and <it>in vitro </it>cytokine production.</p> <p>Results</p> <p>Transient depletion of CD11c<sup>+ </sup>cells during sensitization attenuated airway eosinophilia during allergen challenge and reduced Th2 and Th17 cytokine production. Lung CD11c<sup>+ </sup>cells from wildtype mice exhibited a significant increase in MHCII, CD40, and OX40L expression 2 hours following NO<sub>2 </sub>exposure. By 48 hours, CD11c<sup>+</sup>MHCII<sup>+ </sup>DCs within the mediastinal lymph node (MLN) expressed maturation markers, including CD80, CD86, and OX40L. CD11c<sup>+</sup>CD11b<sup>- </sup>and CD11c<sup>+</sup>CD11b<sup>+ </sup>pulmonary cells exposed to NO<sub>2 </sub><it>in vivo </it>increased uptake of antigen 2 hours post exposure, with increased ova-Alexa 647<sup>+ </sup>CD11c<sup>+</sup>MHCII<sup>+ </sup>DCs present in MLN from NO<sub>2</sub>-exposed mice by 48 hours. Co-cultures of ova-specific CD4<sup>+ </sup>T cells from naïve mice and CD11c<sup>+ </sup>pulmonary cells from NO<sub>2</sub>-exposed mice produced IL-1, IL-12p70, and IL-6 <it>in vitro </it>and augmented antigen-induced IL-5 production.</p> <p>Conclusions</p> <p>CD11c<sup>+ </sup>cells are critical for NO<sub>2</sub>-promoted allergic sensitization. NO<sub>2 </sub>exposure causes pulmonary CD11c<sup>+ </sup>cells to acquire a phenotype capable of increased antigen uptake, migration to the draining lymph node, expression of MHCII and co-stimulatory molecules required to activate naïve T cells, and secretion of polarizing cytokines to shape a Th2/Th17 response.</p
Peripheral Digit Ischemic Syndrome Can Be a Manifestation of Postoperative Thrombotic Thrombocytopenic Purpura
In addition to common dysfunction of the brain and kidney, thrombotic thrombocytopenic purpura (TTP) may present with atypical clinical features due to the involvement of other organs such as the lung, pancreas, heart, eye, and skin. We have also observed the unusual presentation of peripheral digit ischemic syndrome (PDIS) in some patients with postoperative TTP To clarify this relationship between TTP and PDIS, the hematologic data from the medical records of patients with known diagnoses of thrombotic microangiopathy (TM) were examined in a single institution. A total of 94 patients were diagnosed with TM. Among these patients, PDIS developed in six patients and in all these patients PDIS occurred with postoperative TTP Four patients also had acute respiratory distress syndrome (ARDS). Because of delayed diagnosis of TTP, only two patients survived and four died. One patient responded to plasma exchange and survived, and another patient recovered from postoperative TTP without plasma exchange. However, both patients required the amputation of multiple digits. In conclusion, PDIS is another atypical manifestation of TTP and has occurred exclusively in patients with postoperative TTP in this series. Once PDIS developed, the prognosis was poor and amputation of digits was needed in surviving patients. Early recognition of this atypical manifestation of TTP is essential for a favorable outcome
Links Between Hydrothermal Environments, Pyrophosphate, Na+, and Early Evolution
The discovery that photosynthetic bacterial membrane-bound inorganic pyrophosphatase (PPase) catalyzed light-induced phosphorylation of orthophosphate (Pi) to pyrophosphate (PPi) and the capability of PPi to drive energy requiring dark reactions supported PPi as a possible early alternative to ATP. Like the proton-pumping ATPase, the corresponding membrane-bound PPase also is a H+-pump, and like the Na+-pumping ATPase, it can be a Na+-pump, both in archaeal and bacterial membranes. We suggest that PPi and Na+ transport preceded ATP and H+ transport in association with geochemistry of the Earth at the time of the origin and early evolution of life. Life may have started in connection with early plate tectonic processes coupled to alkaline hydrothermal activity. A hydrothermal environment in which Na+ is abundant exists in sediment-starved subduction zones, like the Mariana forearc in the W Pacific Ocean. It is considered to mimic the Archean Earth. The forearc pore fluids have a pH up to 12.6, a Na+-concentration of 0.7 mol/kg seawater. PPi could have been formed during early subduction of oceanic lithosphere by dehydration of protonated orthophosphates. A key to PPi formation in these geological environments is a low local activity of water
Infarto medular diagnóstico clínico, eletrofisiológico e laboratorial: clinical, electrophysiological and laboratory diagnosis
Effectiveness of intervention strategies exclusively targeting reductions in children’s sedentary time: a systematic review of the literature
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