The Role of Demography in the Transition to Sustainable Societies

Currently, although the global population has surpassed 7.5 billion and continues to increase in about 80 million each year, attention to demography is almost absent in most of the studies and publications related to the current situation of planetary emergency and the necessary transition to sustainable societies. For this reason, our first aim in this paper has been to discuss if this current lack of attention to demography is justified or not. With this purpose, we begin considering the scientific meaning of Sustainability, in order to overlay distorted and impoverish views of this concept that may hinder our study. Then, we analyse the reasons given by experts for and against the incidence of demographic growth in the current unsustainable situation of planetary emergency. Finally, we present proposals to face the ensemble of interconnected socio-environmental problems (including demographic evolution), to make possible an appropriate transition to sustainable societies. Aunque la población mundial ha sobrepasado los 7500 millones y continúa aumentando anualmente en alrededor de 80 millones, la atención a la demografía está hoy prácticamente ausente en la mayoría de los estudios y publicaciones acerca de la actual situación de emergencia planetaria y la necesidad de una transición a sociedades sostenibles. Con el propósito de analizar si esta falta de atención a la demografía está o no justificada, en esta contribución comenzamos discutiendo el significado científico de Sostenibilidad socioambiental, para evitar concepciones distorsionadas y empobrecidas de este concepto que pueden dificultar dicho análisis. A continuación estudiaremos las razones dadas por distintos expertos a favor y en contra de la incidencia del crecimiento demográfico en la insostenible situación actual de emergencia planetaria. Finalmente presentamos propuestas para hacer frente al conjunto de problemas estrechamente interconectados - incluido el problema demográfico - que caracterizan dicha situación, para hacer así posible una adecuada transición a sociedades sostenibles

Pion-Lambda-Sigma Coupling Extracted from Hyperonic Atoms

The latest measurements of the atomic level width in Sigma-hyperonic Pb atom offer the most accurate datum in the region of low-energy Sigma-hyperon physics. Atomic widths are due to the conversion of Sigma-nucleon into Lambda-nucleon. In high angular momentum states this conversion is dominated by the one-pion exchange. A joint analysis of the data of the scattering of negative-Sigma on proton converting into a Lambda and a neutron and of the atomic widths allows to extract a pseudovector pion-hyperon-Sigma coupling constant of 0.048 with a statistical error of +-0.005 and a systematic one of +-0.004. This corresponds to a pseudoscalar coupling constant of 13.3 with a statistical uncertainty of 1.4 and a systematic one of 1.1.Comment: 12 pages, 1 figure, Use of Revtex.st

Localization of Events in Space-Time

The present paper deals with the quantum coordinates of an event in space-time, individuated by a quantum object. It is known that these observables cannot be described by self-adjoint operators or by the corresponding spectral projection-valued measure. We describe them by means of a positive-operator-valued (POV) measure in the Minkowski space-time, satisfying a suitable covariance condition with respect to the Poincare' group. This POV measure determines the probability that a measurement of the coordinates of the event gives results belonging to a given set in space-time. We show that this measure must vanish on the vacuum and the one-particle states, which cannot define any event. We give a general expression for the Poincare' covariant POV measures. We define the baricentric events, which lie on the world-line of the centre-of-mass, and we find a simple expression for the average values of their coordinates. Finally, we discuss the conditions which permit the determination of the coordinates with an arbitrary accuracy.Comment: 31 pages, latex, no figure

Structural Basis for Functional Tetramerization of Lentiviral Integrase

Experimental evidence suggests that a tetramer of integrase (IN) is the protagonist of the concerted strand transfer reaction, whereby both ends of retroviral DNA are inserted into a host cell chromosome. Herein we present two crystal structures containing the N-terminal and the catalytic core domains of maedi-visna virus IN in complex with the IN binding domain of the common lentiviral integration co-factor LEDGF. The structures reveal that the dimer-of-dimers architecture of the IN tetramer is stabilized by swapping N-terminal domains between the inner pair of monomers poised to execute catalytic function. Comparison of four independent IN tetramers in our crystal structures elucidate the basis for the closure of the highly flexible dimer-dimer interface, allowing us to model how a pair of active sites become situated for concerted integration. Using a range of complementary approaches, we demonstrate that the dimer-dimer interface is essential for HIV-1 IN tetramerization, concerted integration in vitro, and virus infectivity. Our structures moreover highlight adaptable changes at the interfaces of individual IN dimers that allow divergent lentiviruses to utilize a highly-conserved, common integration co-factor

Entropic Tension in Crowded Membranes

Unlike their model membrane counterparts, biological membranes are richly decorated with a heterogeneous assembly of membrane proteins. These proteins are so tightly packed that their excluded area interactions can alter the free energy landscape controlling the conformational transitions suffered by such proteins. For membrane channels, this effect can alter the critical membrane tension at which they undergo a transition from a closed to an open state, and therefore influence protein function \emph{in vivo}. Despite their obvious importance, crowding phenomena in membranes are much less well studied than in the cytoplasm. Using statistical mechanics results for hard disk liquids, we show that crowding induces an entropic tension in the membrane, which influences transitions that alter the projected area and circumference of a membrane protein. As a specific case study in this effect, we consider the impact of crowding on the gating properties of bacterial mechanosensitive membrane channels, which are thought to confer osmoprotection when these cells are subjected to osmotic shock. We find that crowding can alter the gating energies by more than $2\;k_BT$ in physiological conditions, a substantial fraction of the total gating energies in some cases. Given the ubiquity of membrane crowding, the nonspecific nature of excluded volume interactions, and the fact that the function of many membrane proteins involve significant conformational changes, this specific case study highlights a general aspect in the function of membrane proteins.Comment: 20 pages (inclduing supporting information), 4 figures, to appear in PLoS Comp. Bio

Src-family kinases in the development and therapy of Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphoblastic leukemia

The BCR-ABL kinase inhibitor imatinib has shown significant efficacy in chronic myeloid leukemia (CML) and is the standard front-line therapy for patients in chronic phase. However, a substantial number of patients are either primarily refractory or acquire resistance to imatinib. While a number of mechanisms are known to confer resistance to imatinib, increasing evidence has demonstrated a role for BCR-ABL–independent pathways. The Src-family kinases (SFKs) are one such pathway and have been implicated in imatinib resistance. Additionally, these kinases are key to the progression of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The dual SFK/BCR-ABL inhibitor dasatinib is now clinically available and has markedly greater potency compared with imatinib against native BCR-ABL and the majority of imatinib resistant BCR-ABL mutants. Therefore, this agent, as well as other dual SFK/BCR-ABL inhibitors under development, could provide added therapeutic advantages by overcoming both BCR-ABL– dependent (i.e., BCR-ABL mutations) and – independent forms of imatinib resistance and delaying transition to advanced phase disease. In this review, we discuss the preclinical and clinical evidence demonstrating the involvement of SFKs in imatinib resistance and the progression of CML and Ph+ ALL, as well as the potential role of dual SFK/BCR-ABL inhibition in the management of these diseases

Detecting gene-environment interactions in genome-wide association data

Despite the importance of gene-environment (G×E) interactions in the etiology of common diseases, little work has been done to develop methods for detecting these types of interactions in genome-wide association study data. This was the focus of Genetic Analysis Workshop 16 Group 10 contributions, which introduced a variety of new methods for the detection of G×E interactions in both case-control and family-based data using both cross-sectional and longitudinal study designs. Many of these contributions detected significant G×E interactions. Although these interactions have not yet been confirmed, the results suggest the importance of testing for interactions. Issues of sample size, quantifying the environmental exposure, longitudinal data analysis, family-based analysis, selection of the most powerful analysis method, population stratification, and computational expense with respect to testing G×E interactions are discussed

Transcriptional Profiling of Non-Small Cell Lung Cancer Cells with Activating EGFR Somatic Mutations

Activating somatic mutations in epidermal growth factor receptor (EGFR) confer unique biologic features to non-small cell lung cancer (NSCLC) cells, but the transcriptional mediators of EGFR in this subgroup of NSCLC have not been fully elucidated.Here we used genetic and pharmacologic approaches to elucidate the transcriptomes of NSCLC cell lines. We transcriptionally profiled a panel of EGFR-mutant and -wild-type NSCLC cell lines cultured in the presence or absence of an EGFR tyrosine kinase inhibitor. Hierarchical analysis revealed that the cell lines segregated on the basis of EGFR mutational status (mutant versus wild-type), and expression signatures were identified by supervised analysis that distinguished the cell lines based on mutational status (wild-type versus mutant) and type of mutation (L858R versus Delta746-750). Using an EGFR mutation-specific expression signature as a probe, we mined the gene expression profiles of two independent cohorts of NSCLC patients and found the signature in a subset. EGFR tyrosine kinase inhibitor treatment regulated the expression of multiple genes, and pharmacologic inhibition of the protein products of two of them (PTGS2 and EphA2) inhibited anchorage-independent growth in EGFR-mutant NSCLC cells.We have elucidated genes not previously associated with EGFR-mutant NSCLC, two of which enhanced the clonogenicity of these cells, distinguishing these mediators from others previously shown to maintain cell survival. These findings have potential clinical relevance given the availability of pharmacologic tools to inhibit the protein products of these genes