Epidermal growth factor (EGF)-like repeats of human tenascin-C as ligands for EGF receptor.

Signaling through growth factor receptors controls such diverse cell functions as proliferation, migration, and differentiation. A critical question has been how the activation of these receptors is regulated. Most, if not all, of the known ligands for these receptors are soluble factors. However, as matrix components are highly tissue-specific and change during development and pathology, it has been suggested that select growth factor receptors might be stimulated by binding to matrix components. Herein, we describe a new class of ligand for the epidermal growth factor (EGF) receptor (EGFR) found within the EGF-like repeats of tenascin-C, an antiadhesive matrix component present during organogenesis, development, and wound repair. Select EGF-like repeats of tenascin-C elicited mitogenesis and EGFR autophosphorylation in an EGFR-dependent manner. Micromolar concentrations of EGF-like repeats induced EGFR autophosphorylation and activated extracellular signal-regulated, mitogen-activated protein kinase to levels comparable to those induced by subsaturating levels of known EGFR ligands. EGFR-dependent adhesion was noted when the ligands were tethered to inert beads, simulating the physiologically relevant presentation of tenascin-C as hexabrachion, and suggesting an increase in avidity similar to that seen for integrin ligands upon surface binding. Specific binding to EGFR was further established by immunofluorescence detection of EGF-like repeats bound to cells and cross-linking of EGFR with the repeats. Both of these interactions were abolished upon competition by EGF and enhanced by dimerization of the EGF-like repeat. Such low affinity behavior would be expected for a matrix-tethered ligand; i.e., a ligand which acts from the matrix, presented continuously to cell surface EGF receptors, because it can neither diffuse away nor be internalized and degraded. These data identify a new class of insoluble growth factor ligands and a novel mode of activation for growth factor receptors

Uranium-lead Isotope Evidence in the Shelyabinsk LL5 Chondrite Meteorite for Ancient and Recent Thermal Events

The impact histories on chondrite parent bodies can be deduced from thermochronologic analyses of materials and isotope systems with distinct apparent closure temperatures. It is especially critical to better understand the geological histories and physical properties of potenally hazardous near-Earth asteroids. Chelyabinsk is an LL5 chondrite meteorite that was dispersed over a wide area tens of kilometers south of the town of Chelyabinsk, Russia by an explosion at an altitude of 27 km at 3:22 UT on 15 Feb 2013 [1,2]. The explosion resulted in significant damage to surrounding areas and over 1500 injuries along with meteorite fragments being spread over a wide area [1]

Amazonian Hydrothermal Alteration Comparing Nakhlite Secondary Mineralogy to Water Rock Reaction Experiments

We report on results from experiments with Mars analog materials under diagenetic conditions. The mineralogical results of our experiments suggest that an important type of fluid alteration in the Amazonian may be short duration (e.g. less than 1 year) events from near neutral, dilute brines, that were able to exchange CO2 either directly, or via ice reservoirs, with the atmosphere

Mineral Surface and Fluid Chemistry in Nakhlite Analog Water-Rock Reactions

We report on experiments with Mars analog materials under diagenetic conditions and find characteristic chemical surface changes in correspondence with the fluid conditions

Human papillomavirus 16 L2 inhibits the transcriptional activation function, but not the DNA replication function, of HPV-16 E2

In this study we analysed the outcome of the interaction between HPV-16 L2 and E2 on the transactivation and DNA replication functions of E2. When E2 was expressed on its own, it transactivated a number of E2-responsive promoters but co-expression of L2 led to the down-regulation of the transcription transactivation activity of the E2 protein. This repression is not mediated by an increased degradation of the E2 protein. In contrast, the expression of L2 had no effect on the ability of E2 to activate DNA replication in association with the viral replication factor E1. Deletion mutagenesis identified L2 domains responsible for binding to E2 (first 50 N-terminus amino acid residues) and down-regulating its transactivation function (residues 301–400). The results demonstrate that L2 selectively inhibits the transcriptional activation property of E2 and that there is a direct interaction between the two proteins, although this is not sufficient to mediate the transcriptional repression. The consequences of the L2–E2 interaction for the viral life cycle are discussed

Fractionated noble gases in the nakhlite Martian meteorites

Noble gases measured in Martian meteorites are frequently a mixture of different components, ranging from Martian interior and unfractionated and fractionated atmosphere, to cosmic ray produced isotopes and terrestrial contamination. Here we focus on the Martian components, especially the fractionated Martian atmosphere in the nakhlite meteorites, in comparison to the other Martian components

Fractionated Martian Atmosphere – the Case of the Nakhlites, Revisited with Experiments

We report on fractionated noble gases in the Martian meterorites - a literature survey and new data

Curie: Constraining Solar System Bombardment Using In Situ Radiometric Dating

The Curie mission would constrain the existence of the putative cataclysm by determining the age of samples directly sourced from the impact melt sheet of a major pre-Imbrium lunar basin. The measurements would also enable further understanding of lunar evolution by characterizing new lunar lithologies far from the Apollo and Luna landing sites, including the very low-Ti basalts in Mare Crisium and potential olivine rich lithologies in the margins of both Mare Nectaris and Mars Crisium. Equipped with a mass spectrometer and a LIBS, Curie would also be well-placed to survey volatile components of the lunar regolith, including surface-bound hydrogen

Ar-Ar Analysis of Chelyabinsk: Evidence for a Recent Impact

The Chelyabinsk meteorite is an LL5 ordinary chondrite that fell as a spectacular fireball on February 15th, 2013, over the Ural region in Russia. The meteoroid exploded at an altitude of 25-30 km, producing shockwaves that broke windowpanes in Chelyabinsk and surrounding areas, injuring some 1500 people. Analyses of the samples show that the meteorite underwent moderate shock metamorphism (stage S4; 25-35 GPa) [1]. Most of the samples have a fusion crust ranging from ~0.1-1mm thick, and roughly a third of the samples were composed of a dark fine-grained impact melt with chondrule fragments which were targeted for chronometry. A Pb-Pb age obtained by [2] of a shock-darkened and potentially melted sample of Chelyabinsk is reported as 4538.3 +/- 2.1 Ma, while a U-Pb study [3] gave an upper concordia intercept of 4454 +/- 67 Ma and a lower intercept of 585 +/- 390. Galimov et al. 2013 [1] suggest the Sm-Nd system records a recent impact event [~290 Ma] that may represent separation from the parent body, while the Rb-Sr isotopic system is disturbed and does not give any definitive isochron. In order to better understand its history, we have performed 40Ar-39Ar analysis on multiple splits of two Chelyabinsk samples; clast- rich MB020f,2 and melt-rich MB020f,5. The term "clast-rich" lithology is meant to indicate a mechanical mixture of highly shock-darkened and less shocked components, both with some shock melt veining

Earth-Moon Impacts at ~300 Ma and ~500 Ma Ago

Impact events have played an important role in the evolution of planets and small bodies in the Solar System. Meteorites, lunar melt rocks, and lunar impact glasses provide important information about the geology of the parent body and the age of the impacting episodes. Over 2400 impact glasses from 4 Apollo regolith samples have been geochemically analyzed and a subset has been dated by the (40)Ar/(39)Ar method. New results, consistent with 2 break-ups in the Asteroid Belt, are presented here. Our previous study reported that (40)Ar/(39)Ar ages from 9 impact glasses showed that the Moon experienced significant impacts at approx. 800 Ma and at approx. 3800 Ma ago, somewhere in the vicinity of the Apollo 16 landing site. Additionally, reported on Apollo 12 samples with ages around 800 Ma, together implying global bombardment events. New data on 7 glasses from regolith sample 66041,127 show that the Moon also experienced impact events at approx. 300 Ma and > 500 Ma ago, which may coincide with the break-ups in the Asteroid Belt of the L- and H-chrondrite parent bodies. Since meteoritic evidence for these breakups has been found on Earth, it follows that evidence should be found in lunar samples as well. Additional information is included in the original extended abstract