PLEKHS1 drives PI3Ks and remodels pathway homeostasis in PTEN-null prostate

The PIP3/PI3K network is a central regulator of metabolism and is frequently activated in cancer, commonly by loss of the PIP3/PI(3,4)P2 phosphatase, PTEN. Despite huge research investment, the drivers of the PI3K network in normal tissues and how they adapt to overactivation are unclear. We find that in healthy mouse prostate PI3K activity is driven by RTK/IRS signaling and constrained by pathway feedback. In the absence of PTEN, the network is dramatically remodeled. A poorly understood YXXM- and PIP3/PI(3,4)P2-binding PH domain-containing adaptor, PLEKHS1, became the dominant activator and was required to sustain PIP3, AKT phosphorylation, and growth in PTEN-null prostate. This was because PLEKHS1 evaded pathway-feedback and experienced enhanced PI3K- and Src-family kinase-dependent phosphorylation of Y258XXM, eliciting PI3K activation. hPLEKHS1 mRNA and activating Y419 phosphorylation of hSrc correlated with PI3K pathway activity in human prostate cancers. We propose that in PTEN-null cells receptor-independent, Src-dependent tyrosine phosphorylation of PLEKHS1 creates positive feedback that escapes homeostasis, drives PIP3 signaling, and supports tumor progression

Efficient Coding and Statistically Optimal Weighting of Covariance among Acoustic Attributes in Novel Sounds

To the extent that sensorineural systems are efficient, redundancy should be extracted to optimize transmission of information, but perceptual evidence for this has been limited. Stilp and colleagues recently reported efficient coding of robust correlation (r = .97) among complex acoustic attributes (attack/decay, spectral shape) in novel sounds. Discrimination of sounds orthogonal to the correlation was initially inferior but later comparable to that of sounds obeying the correlation. These effects were attenuated for less-correlated stimuli (r = .54) for reasons that are unclear. Here, statistical properties of correlation among acoustic attributes essential for perceptual organization are investigated. Overall, simple strength of the principal correlation is inadequate to predict listener performance. Initial superiority of discrimination for statistically consistent sound pairs was relatively insensitive to decreased physical acoustic/psychoacoustic range of evidence supporting the correlation, and to more frequent presentations of the same orthogonal test pairs. However, increased range supporting an orthogonal dimension has substantial effects upon perceptual organization. Connectionist simulations and Eigenvalues from closed-form calculations of principal components analysis (PCA) reveal that perceptual organization is near-optimally weighted to shared versus unshared covariance in experienced sound distributions. Implications of reduced perceptual dimensionality for speech perception and plausible neural substrates are discussed

Towards Sustainable Development in Rural Africa

. A growing recognition of the need to delimit the role of the government, to promote the market framework, and to rely on the private sector as the engine of growth, offers the prospect of a new beginning in rural development in Africa. . Rural people must take a more dominant role, both in shaping their economic prospects and in assuming the responsibility for a high quality of stewardship of natural resources. . To help to bring about such an empowerment of the people, governments and the donors will need to undertake some drastic reforms in the old systems and habits of governance.

Managing the Environment in Developing Countries

• Environmental policy should be inspired by the recognition that the environment is everyone’s business; all social actors must be involved in environmental management • Policies that implicitly subsidize a wasteful and environmentally destructive use of resources are pervasive: reforms should command a high priority on economic as well as environmental grounds • Compared to regulation, market-based instruments are little used but they can be more efficient; they can also produce revenues to finance environmental improvements • Regulatory effectiveness can be improved by: relying more on preventive measures, including environmental impact assessment; targeting large polluters; strengthening enforcement; and favouring mediation over litigation

Gestion de l'environnement dans les pays en développement

• La politique de l'environnement devrait être fondée sur le principe selon lequel l'environnement est l'affaire de chacun ; tous les acteurs sociaux doivent prendre part à la gestion de l'environnement • Les politiques qui encouragent mplicitement, par des subventions, une exploitation des ressources naturelles abusive et préjudiciable à l'environnement sont fréquentes : les réformes devraient donner aussi bien la priorité aux questions économiques qu'à celles concernant l'environnement • Les instruments de marché sont moins employés que la réglementation mais ils peuvent être plus efficaces ; ils peuvent également constituer une source de revenus pour le financement de la protection de l'environnement • Il est possible d'améliorer l'efficacité des réglementations en mettant l'accent sur les mesures préventives, notamment les études d'impact sur l'environnement, en identifiant les gros pollueurs, en renforçant la mise en oeuvre des mesures adoptées et en encourageant la médiation aux dépens du recours à la poursuite judiciaire

Unemployment in Developing Countries: New Light on an Old Problem

In the 1960s and 1970s a number of views were formed about unemployment in developing countries, which have remained largely accepted since then. The views can be summarized as three propositions: a) the poor cannot afford to become unemployed; b) labour markets in developing countries are always sufficiently open and flexible for work to be found, so that c) unemployment is a reflection of the search for jobs with high earnings on the part of those able to finance search costs. In contrast, the conclusions of this review are that the poor can be and are increasingly to be found in large numbers among the unemployed; many young people have great difficulty in finding any sort of work, especially regular work; unemployment is high and appears to have been rising over the past 20 years. In sum, in the light of this review of evidence, the conventional wisdom described in the so-called luxury unemployment hypothesis is seriously flawed and should be set aside. Les années 60 et 70 ont vu naître, dans les pays en développement, nombre d'idées sur le chômage, qui, depuis lors, restent largement admises. Trois propositions en résument le contenu : a) les pauvres ne peuvent pas se permettre de devenir chômeurs ; b) le marché du travail dans les pays en développement est toujours suffisamment ouvert et flexible pour qu'on y trouve du travail ; c) de ce fait, le chômage provient de la recherche d'emplois à hauts salaires de la part des couches sociales capables de financer le coût de leur quête de travail. Contrairement aux idées reçues, cette étude conclut que ce sont les pauvres qui figurent, et ce, de façon croissante, parmi les chômeurs ; quantité de jeunes éprouvent de grandes difficultés à trouver quelque travail que ce soit, surtout un emploi régulier ; le chômage est élevé et n'a cessé de progresser au cours des vingt dernières années. L'hypothèse d'un chômage qu'on pourrait appeler "de luxe" se révèle donc insuffisante, voire ...

Revival of Philozoon Geddes for host-specialized dinoflagellates, ‘zooxanthellae’, in animals from coastal temperate zones of northern and southern hemispheres

The dinoflagellate family Symbiodiniaceae comprises numerous genera and species with large differences in diversity, ecology and geographic distribution. An evolutionarily divergent lineage common in temperate symbiotic cnidarians and designated in the literature by several informal names including ‘temperate–A’, AI, Phylotype A´ (A-prime) and ‘Mediterranean A’, is here assigned to the genus Philozoon. This genus was proposed by Geddes (1882) in one of the earliest papers that recognized ‘yellow cells’ as distinct biological entities separate from their animal and protist hosts. Using phylogenetic data from nuclear (rDNA), chloroplast (cp23S) and mitochondrial genes (cob and cox1), as well as morphology (cell size), ecological traits (host affinity) and geographic distributions, we emend the genus Philozoon Geddes and two of its species, P. medusarum and P. actiniarum, and describe six new species. Each symbiont species exhibits high host fidelity for particular species of sea anemone, soft coral, stony coral and a rhizostome jellyfish. Philozoon is most closely related to Symbiodinium (formerly Clade A), but, unlike its tropical counterpart, occurs in hosts in shallow temperate marine habitats in northern and southern hemispheres including the Mediterranean Sea, north-eastern Atlantic Ocean, eastern Australia, New Zealand and Chile. The existence of a species-diverse lineage adapted to cnidarian hosts living in high latitude habitats with inherently wide fluctuations in temperature calls further attention to the ecological and biogeographic reach of the Symbiodiniaceae