MEK Partner 1 (MP1): Regulation of oligomerization in MAP kinase signaling

Specificity in signal transduction can be achieved through scaffolds, anchors, and adapters that assemble generic signal transduction components in specific combinations and locations. MEK Partner-1 (MP1) was identified as a potential "scaffold" protein for the mammalian extracellular signal-regulated kinase (ERK) pathway. To gain insight into the interactions of MP1 with the ERK pathway, we analyzed the ability of MP1 to bind to MEK1, ERK1, and to itself, and the regulation of these interactions. Gel filtration of cell lysates revealed two major MP1 peaks: a broad high molecular weight peak and a 28 kDa complex. An MP1 mutant that lost MEK1 binding no longer enhanced RasV12-stimulated ERK1 activity, and functioned as a dominant negative, consistent with the concept that MP1 function depends on facilitating these oligomerizations. Activation of the ERK pathway by serum or by RasV12 did not detectably affect MP1-MP1 dimerization or MP1-MEK1 interactions, but caused the dissociation of the MP1-ERK1 complex. Surprisingly, pharmacological inhibition of ERK activation did not restore the complex, suggesting that regulation of complex formation occurs independently of ERK phosphorylation. These results support the concept that MP1 functions as a regulator of MAP kinase signaling by binding to MEK1 and regulating its association with a larger signaling complex that may sequentially service multiple molecules of ERK

Intrinsic passive stiffness of 2 constructs of varus proximal femoral osteotomy: External fixator or blade plate

Background: Despite the published clinical evidence of the implementation of external fixation of proximal femoral osteotomies, there is lack of specific laboratory justification. Methods: Two groups of 5 adult composite femur constructs of varus proximal femoral osteotomy were tested under incremental and cyclical loading of up to 600N along the mechanical axis. Five were fixed with a blade plate and another 5 with a monolateral external fixator. Load versus displacement curves were produced, and passive stiffness of all constructs was calculated. The described loading regime aimed to simulate the initial postoperative state and provide data for the assessment of vertical intrinsic passive stiffness in partial weight-bearing conditions. Results: Although the blade plate constructs showed higher average stiffness, this was not statistically significant [F(1,8) = 1.712, P = 0.23]. No construct failed. No failure or plastic deformation was observed under the described loading regime. Conclusions: Vertical intrinsic passive stiffness in partial weight- bearing conditions during the initial postoperative period can be considered satisfactory subsequent to unilateral external fixation of a varus intertrochanteric osteotomy. Clinical Relevance: The results support the hypothesis that external fixation is a biomechanically sound alternative to internal fixation of varus intertrochanteric osteotomies, in selected patients. Copyright © 2010 by Lippincott Williams & Wilkins

Predicting and assessing progress in the restoration of ecosystems

Restoration of degraded landscapes has become necessary to reverse the pervasive threats from human exploitation. Restoration requires first the monitoring of progress toward any chosen goals to determine their resilience and persistence, and second to conduct in a comparable adjacent area but with less human impact the restoration of trophic structures and ecosystem processes to act as reference systems (controls) with which we compare the viability of the chosen goal. We present here the rationale and a method for predicting the trajectory of restoration and assessing its progress toward a predetermined state, the endpoint, using a restoration index. This assessment of restoration requires that we know when a predetermined endpoint has been achieved and whether the envisioned community of species and their interactions can be restored. The restoration index can use species’ presence or density, and the rate of change of ecosystem processes. The index applies to trophic levels, functional groups, successional stages, alternative states, and novel ecosystems. Also, our method allows measurement of the resilience of ecosystems to disturbance, a desired property for conservation and management. We provide global examples to illustrate these points

An indirect evidence of piezonuclear fission reactions: Geomechanical and geochemical evolution in the Earth's Crust

Piezonuclear reactions, which occur in inert and nonradioactive elements, are induced by high pressure and, in particular, by brittle fracture phenomena in solids under compression. These low energy reactions generally take place in nuclei with an atomic weight that is lower or equal to that of iron (Fe). The experimental evidence, obtained from repeatable measurements of neutron emissions, can be also recognized considering the anomalous chemical balances of the major events that have affected the Earth's crust, oceans and atmosphere, over the last four billion years. These anomalies include: (i) the abrupt variations in the most abundant elements in correspondence to the formation of tectonic plates; (ii) the Great Oxidation Event (2.7 to 2.4 billion years ago), with a sharp increase in atmospheric oxygen and the subsequent origin of life; (iii) the increase of carbon and nytrogen concentrations in the primordial atmospher

Selection of the InSight Landing Site

The selection of the Discovery Program InSight landing site took over four years from initial identification of possible areas that met engineering constraints, to downselection via targeted data from orbiters (especially Mars Reconnaissance Orbiter (MRO) Context Camera (CTX) and High-Resolution Imaging Science Experiment (HiRISE) images), to selection and certification via sophisticated entry, descent and landing (EDL) simulations. Constraints on elevation (≤−2.5 km for sufficient atmosphere to slow the lander), latitude (initially 15°S–5°N and later 3°N–5°N for solar power and thermal management of the spacecraft), ellipse size (130 km by 27 km from ballistic entry and descent), and a load bearing surface without thick deposits of dust, severely limited acceptable areas to western Elysium Planitia. Within this area, 16 prospective ellipses were identified, which lie ∼600 km north of the Mars Science Laboratory (MSL) rover. Mapping of terrains in rapidly acquired CTX images identified especially benign smooth terrain and led to the downselection to four northern ellipses. Acquisition of nearly continuous HiRISE, additional Thermal Emission Imaging System (THEMIS), and High Resolution Stereo Camera (HRSC) images, along with radar data confirmed that ellipse E9 met all landing site constraints: with slopes \u3c15° at 84 m and 2 m length scales for radar tracking and touchdown stability, low rock abundance (\u3c10 %) to avoid impact and spacecraft tip over, instrument deployment constraints, which included identical slope and rock abundance constraints, a radar reflective and load bearing surface, and a fragmented regolith ∼5 m thick for full penetration of the heat flow probe. Unlike other Mars landers, science objectives did not directly influence landing site selection