A pre-metazoan origin of the CRK gene family and co-opted signaling network.

CRK and CRKL adapter proteins play essential roles in development and cancer through their SRC homology 2 and 3 (SH2 and SH3) domains. To gain insight into the origin of their shared functions, we have investigated their evolutionary history. We propose a term, crk/crkl ancestral (crka), for orthologs in invertebrates before the divergence of CRK and CRKL in the vertebrate ancestor. We have isolated two orthologs expressed in the choanoflagellate Monosiga brevicollis, a unicellular relative to the metazoans. Consistent with its highly-conserved three-dimensional structure, the SH2 domain of M. brevicollis crka1 can bind to the mammalian CRK/CRKL SH2 binding consensus phospho-YxxP, and to the SRC substrate/focal adhesion protein BCAR1 (p130(CAS)) in the presence of activated SRC. These results demonstrate an ancient origin of the CRK/CRKL SH2-target recognition specificity. Although BCAR1 orthologs exist only in metazoans as identified by an N-terminal SH3 domain, YxxP motifs, and a C-terminal FAT-like domain, some pre-metazoan transmembrane proteins include several YxxP repeats in their cytosolic region, suggesting that they are remotely related to the BCAR1 substrate domain. Since the tyrosine kinase SRC also has a pre-metazoan origin, co-option of BCAR1-related sequences may have rewired the crka-dependent network to mediate adhesion signals in the metazoan ancestor

Youth in the Maldives : Shaping a New Future for Young Women and Men through Engagement and Empowerment

This report responds to the growing concern over issues facing Maldivian youth today, and specifically, to a request made by the Ministry of Youth and Sports to examine the status of youth in the Maldives. Such concerns are certainly warranted, particularly in light of a regional youth bulge which is taking place in South Asia, as well as an observed increase in at risk behavior such as youth drug use and membership in gangs. While a number of studies have sought to examine youth issues in the Maldives, a comprehensive and holistic assessment is lacking. This report was aimed at helping to fill this knowledge gap. This report examines issues affecting young people in the Maldives as they transition from adolescence to adulthood, and based on this analysis and a review of international good practice, recommends a number of actions for the Government s consideration. The analysis focused on youth experiences as they pertain to: health, education, labor, family structure, gangs and violence, and civic engagement and participation. A youth development framework, based on public health literature and adapted to the Maldives, serves as the organizing structure of the report. The report draws on original data collection and analysis, as well as an extensive review of existing literature. With regard to data collection, the study involved field-based research including a household survey and in-depth interviews, and focus-group discussions with youth and stakeholders in the Maldives

Territorial Extrapolation of Basic Data as a Solution of the Problem of Its Deficiency during Mass Appraisal

The article is devoted to the application of the territorial extrapolation of basic data method during a mass (cadastral) assessment of a territory that is characterized by an acute lack of market information. In the framework of the study, an acute lack is understood as the conditions when for the assessing territory there are less than five transaction (offer) prices suitable for regression models. The idea of the method is to use market information of territories that are comparable in a composition of pricing factors and the nature of their influence on the cost, as well as in terms of price levels. The developed method includes such stages as collection of basic data, creation of thematic maps, grouping of estimated territories by price level and composition of pricing factors and modeling. The method was applied to assess land plots that have the type of permitted use “for individual housing construction” and belong to the mass appraisal segment “gardening and horticulture, low-rise residential buildings” in the settlements of the Republic of Udmurtia. The results of approbation shown that the method of territorial extrapolation helps to overcome an acute shortage of market information and build statistically significant models of the cadastral values of land plots

Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons

Adhesion-type G protein-coupled receptors (aGPCRs), a large molecule family with over 30 members in humans, operate in organ development, brain function and govern immunological responses. Correspondingly, this receptor family is linked to a multitude of diverse human diseases. aGPCRs have been suggested to possess mechanosensory properties, though their mechanism of action is fully unknown. Here we show that the Drosophila aGPCR Latrophilin/dCIRL acts in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step of cellular mechanosensation. This process depends on the length of the extended ectodomain and the tethered agonist of the receptor, but not on its autoproteolysis, a characteristic biochemical feature of the aGPCR family. Intracellularly, dCIRL quenches cAMP levels upon mechanical activation thereby specifically increasing the mechanosensitivity of neurons. These results provide direct evidence that the aGPCR dCIRL acts as a molecular sensor and signal transducer that detects and converts mechanical stimuli into a metabotropic response

Where Brain, Body and World Collide

The production cross section of electrons from semileptonic decays of beauty hadrons was measured at mid-rapidity (|y| < 0.8) in the transverse momentum range 1 < pt < 8 Gev/c with the ALICE experiment at the CERN LHC in pp collisions at a center of mass energy sqrt{s} = 7 TeV using an integrated luminosity of 2.2 nb^{-1}. Electrons from beauty hadron decays were selected based on the displacement of the decay vertex from the collision vertex. A perturbative QCD calculation agrees with the measurement within uncertainties. The data were extrapolated to the full phase space to determine the total cross section for the production of beauty quark-antiquark pairs

Plasmonic-Based Mechanochromic Microcapsules as Strain Sensors

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