Bicc1 links the regulation of cAMP signaling in polycystic kidneys to microRNA-induced gene silencing.

Genetic defects in autosomal-dominant polycystic kidney disease (ADPKD) promote cystic growth of renal tubules, at least in part by stimulating the accumulation of cAMP. How renal cAMP levels are regulated is incompletely understood. We show that cAMP and the expression of its synthetic enzyme adenylate cyclase-6 (AC6) are up-regulated in cystic kidneys of Bicc1(-)(/-) knockout mice. Bicc1, a protein comprising three K homology (KH) domains and a sterile alpha motif (SAM), is expressed in proximal tubules. The KH domains independently bind AC6 mRNA and recruit the miR-125a from Dicer, whereas the SAM domain enables silencing by Argonaute and TNRC6A/GW182. Bicc1 similarly induces silencing of the protein kinase inhibitor PKIα by miR-27a. Thus, Bicc1 is needed on these target mRNAs for silencing by specific miRNAs. The repression of AC6 by Bicc1 might explain why cysts in ADPKD patients preferentially arise from distal tubules.

STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing.

Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c(+) cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific deletion of STAT3 activity were highly susceptible to experimental colitis, indicating that epithelial STAT3 regulates gut homeostasis. STAT3(IEC-KO) mice, upon induction of colitis, showed a striking defect of epithelial restitution. Gene chip analysis indicated that STAT3 regulates the cellular stress response, apoptosis, and pathways associated with wound healing in IECs. Consistently, both IL-22 and epithelial STAT3 were found to be important in wound-healing experiments in vivo. In summary, our data suggest that intestinal epithelial STAT3 activation regulates immune homeostasis in the gut by promoting IL-22-dependent mucosal wound healing.

Generation of cell polarity in plants links endocytosis, auxin distribution and cell fate decisions.

Dynamically polarized membrane proteins define different cell boundaries and have an important role in intercellular communication-a vital feature of multicellular development. Efflux carriers for the signalling molecule auxin from the PIN family are landmarks of cell polarity in plants and have a crucial involvement in auxin distribution-dependent development including embryo patterning, organogenesis and tropisms. Polar PIN localization determines the direction of intercellular auxin flow, yet the mechanisms generating PIN polarity remain unclear. Here we identify an endocytosis-dependent mechanism of PIN polarity generation and analyse its developmental implications. Real-time PIN tracking showed that after synthesis, PINs are initially delivered to the plasma membrane in a non-polar manner and their polarity is established by subsequent endocytic recycling. Interference with PIN endocytosis either by auxin or by manipulation of the Arabidopsis Rab5 GTPase pathway prevents PIN polarization. Failure of PIN polarization transiently alters asymmetric auxin distribution during embryogenesis and increases the local auxin response in apical embryo regions. This results in ectopic expression of auxin pathway-associated root-forming master regulators in embryonic leaves and promotes homeotic transformation of leaves to roots. Our results indicate a two-step mechanism for the generation of PIN polar localization and the essential role of endocytosis in this process. It also highlights the link between endocytosis-dependent polarity of individual cells and auxin distribution-dependent cell fate establishment for multicellular patterning.

Quantization of energy and writhe in self-repelling knots

Probably the most natural energy functional to be considered for knotted strings is that given by electrostatic repulsion. In the absence of counter-charges, a charged, knotted string evolving along the energy gradient of electrostatic repulsion would progressively tighten its knotted domain into a point on a perfectly circular string. However, in the presence of charge screening self-repelling knotted strings can be stabilized. It is known that energy functionals in which repulsive forces between repelling charges grow inversely proportionally to the third or higher power of their relative distance stabilize self-repelling knots. Especially interesting is the case of the third power since the repulsive energy becomes scale invariant and does not change upon Mobius transformations (reflections in spheres) of knotted trajectories. We observe here that knots minimizing their repulsive Mobius energy show quantization of the energy and writhe (measure of chirality) within several tested families of knots.

Normal forms, stability and splitting of invariant manifolds I. Gevrey Hamiltonians

In this paper, we give a new construction of resonant normal forms with a small remainder for near-integrable Hamiltonians at a quasi-periodic frequency. The construction is based on the special case of a periodic frequency, a Diophantine result concerning the approximation of a vector by independent periodic vectors and a technique of composition of periodic averaging. It enables us to deal with non-analytic Hamiltonians, and in this first part we will focus on Gevrey Hamiltonians and derive normal forms with an exponentially small remainder. This extends a result which was known for analytic Hamiltonians, and only in the periodic case for Gevrey Hamiltonians. As applications, we obtain an exponentially large upper bound on the stability time for the evolution of the action variables and an exponentially small upper bound on the splitting of invariant manifolds for hyperbolic tori, generalizing corresponding results for analytic Hamiltonians.

Normal forms, stability and splitting of invariant manifolds II. Finitely differentiable Hamiltonians

This paper is a sequel to ``Normal forms, stability and splitting of invariant manifolds I. Gevrey Hamiltonians", in which we gave a new construction of resonant normal forms with an exponentially small remainder for near-integrable Gevrey Hamiltonians at a quasi-periodic frequency, using a method of periodic approximations. In this second part we focus on finitely differentiable Hamiltonians, and we derive normal forms with a polynomially small remainder. As applications, we obtain a polynomially large upper bound on the stability time for the evolution of the action variables and a polynomially small upper bound on the splitting of invariant manifolds for hyperbolic tori.

Evaluation of a modified Broström-Gould procedure for treatment of chronic lateral ankle instability: A retrospective study with critical analysis of outcome scoring.

BACKGROUND: Chronic lateral ankle instability accounts for 20% of the ankle injuries. This study evaluates functional outcome of the modified Broström-Gould technique using suture anchors, with 4 different clinical scores. METHODS: A consecutive series of 41 patients were included with a minimum follow-up of one year. The function was assessed using 4 clinical scores including: the AOFAS for hind foot; the FAAM; the CAIT and the CAIS. RESULTS: Out of 41 patients; 27 patients were very satisfied, 11 satisfied and 3 were not satisfied. Ankle mobility returned to normal in 93% of patients. At follow-up the AOFAS was 89/100 (37-100), the FAAM 85/100% (35-100%), the CAIT 20/30 (5-30), and the CAIS 74/100% (27-100%). CONCLUSION: Outcome of modified Broström-Gould procedure is good with high satisfaction rate in terms of ankle mobility. The disparity in outcome of scores, signals towards the need of a standard evaluation system.

The human Ia-associated invariant chain is synthesized in Ia-negative B cell variants and is not expressed on the cell surface of both Ia-negative and Ia-positive parental cells.

The expression of Ia-associated human Invariant (In) chain glycoproteins was studied in the Raji B cells as well as in their RJ 2.2.5 Ia-negative derived variant cells by using a specific rabbit anti-human In chain antiserum. Two-dimensional gel electrophoresis of immunoprecipitates from either biosynthetically labeled or surface labeled cells were analyzed. In addition, flow microfluorometric analysis of stained cells was performed. The results indicate that the In chain is constitutively produced in the Ia-negative B cell variant. Moreover, it appears that several forms of In chain-related molecules, with different charges and distinct m.w. are equally expressed in Ia-positive and Ia-negative B cells. Finally, no evidence could be obtained that the In molecular family was expressed on the cell surface of Ia-positive Raji and Ia-negative RJ 2.2.5 cells.

The “Death of environmentalism” debates: forging links between SEA and civil society discourses

Social and environmental accounting (SEA) is currently going through a period of critical selfanalysis.Challenging questions are being raised about how SEA should be defined, who should be doing the defining, and what the agenda should be. We attempt to engage and enrich these debates from both a process and content perspective by drawing on the political philosophy of agonistic pluralism and a set of debates within the environmental movement – “the death of environmentalism” debates. The contribution of the paper is twofold: to set forth the death of environmentalism debates in the accounting literature and, in doing so, to contextualize and theorize the contested nature of SEA using agonistic pluralism. In contrast to consensually oriented approaches to SEA, the desired outcome is not necessarily resolution of ideological differences but to imagine, develop, and support democratic processes wherein these differences can be recognized and engaged. We construe the “Death” debates as illustrative of the contestable practical and political issues facing both SEA and progressive social movements generally, demonstrating the context and content of the deliberations necessary in contemplating effective programs of engagement. The SEA community, and civil society groups, can benefit from the more overtly political perspective provided by agonistic pluralism. By surfacing and engaging with various antagonisms in this wider contested civic sphere, SEA can more effectively respond to, and move beyond, traditional politically conservative, managerialist approaches to sustainability.

Topographical body fat distribution links to amino acid and lipid metabolism in healthy non-obese women.

Visceral adiposity is increasingly recognized as a key condition for the development of obesity related disorders, with the ratio between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) reported as the best correlate of cardiometabolic risk. In this study, using a cohort of 40 obese females (age: 25-45 y, BMI: 28-40 kg/m(2)) under healthy clinical conditions and monitored over a 2 weeks period we examined the relationships between different body composition parameters, estimates of visceral adiposity and blood/urine metabolic profiles. Metabonomics and lipidomics analysis of blood plasma and urine were employed in combination with in vivo quantitation of body composition and abdominal fat distribution using iDXA and computerized tomography. Of the various visceral fat estimates, VAT/SAT and VAT/total abdominal fat ratios exhibited significant associations with regio-specific body lean and fat composition. The integration of these visceral fat estimates with metabolic profiles of blood and urine described a distinct amino acid, diacyl and ether phospholipid phenotype in women with higher visceral fat. Metabolites important in predicting visceral fat adiposity as assessed by Random forest analysis highlighted 7 most robust markers, including tyrosine, glutamine, PC-O 44∶6, PC-O 44∶4, PC-O 42∶4, PC-O 40∶4, and PC-O 40∶3 lipid species. Unexpectedly, the visceral fat associated inflammatory profiles were shown to be highly influenced by inter-days and between-subject variations. Nevertheless, the visceral fat associated amino acid and lipid signature is proposed to be further validated for future patient stratification and cardiometabolic health diagnostics.

Correction: Topographical Body Fat Distribution Links to Amino Acid and Lipid Metabolism in Healthy Obese Women.

This corrects the article on p. e73445 in vol. 8.]. This corrects the article "Topographical Body Fat Distribution Links to Amino Acid and Lipid Metabolism in Healthy Non-Obese Women" , e73445. There was an error in the title of the article. The correct version of the title in the article is: Topographical Body Fat Distribution Links to Amino Acid and Lipid Metabolism in Healthy Obese Women The correct citation is: Martin F-PJ, Montoliu I, Collino S, Scherer M, Guy P, et al. (2013) Topographical Body Fat Distribution Links to Amino Acid and Lipid Metabolism in Healthy Obese Women. PLoS ONE 8(9): e73445. doi:10.1371/journal.pone.0073445

Avaliação dos Serviços VoIP em Links de Baixa Capacidade com Tráfego Compartilhado de Dados

Esta dissertação descreve os resultados das medições observadas em um dos Laboratórios de uma Operadora de Telecomunicações (LOP), onde foram avaliados e analisados alguns requisitos de QoS em redes de pacotes IP (Internet Protocol). Essas medições foram feitas no âmbito do objetivo desta dissertação que é avaliar formas de prover serviços VoIP (Voice over Internet Protocol) em redes de pacotes conforme a recomendação do padrão FRF.12. Essa rede é assim, uma rede de link de 512kbps que também provê serviços VoIP compartilhados, concorrentemente com dados e serviços multimídia. Dos ítens analisados destacam-se: Análise de Codecs; QoS (Quality Of Service) Diffserv; Compressão de cabeçalho RTP (Real Time Protocol) - cRTP; Fragmentação com intercalação - LFI; Comportamento da Rede em situações diversas; a adequação do software free Multi Generator (MGEN) de geração - medição - coleta de dados, em redes. A análise foi, essencialmente, em enlace Frame Relay nos CPE (Customer Premise Equipment), passando pelo Backbone IP VPN / MPLS Multicast, pois o Frame Relay Fórum v12 (FRF.12) dá suporte à intercalação de voz entre os pacotes de dados. O FRF.12 é indispensável, pois este esta dissertação tem como objetivo realizar um conjuntos de testes e medidas que avaliam a aplicação dos serviços VoIP em links de baixa capacidades com trafego de dados compartilhados. Para oferecer esse serviço e de qualidade é necessário fragmentar e intercalar frames de voz entre os pacotes de dados usando o FRF.12. Depois do estudo teórico das recomendações, normas de padronização internacional e dos fabricantes, foram realizados testes que resultam na validação prática de toda a teoria outrora analisada através de testes específicos que comprovam em definitivo a viabilidade das aplicações VoIP em uma rede de enlace de baixa velocidade. Feitos esses testes chegou-se a conclusão de que em determinados casos não se revela necessário nem preocupante o aumento da banda para se puder prover determinados serviços. Na sequência dos testes foram também avaliados o desempenho, a ocupação da banda e a eficácia dos equipamentos - softwares. Da bancada dos testes e medições, provou-se o seguinte: que de fato consegue-se melhor otimização da banda ao realizar compressão do cabeçalho cRTP; que de fato a fragmentação de pacote FTP (File Transfer Protocol) com intercalação de pacotes VoIP faz reduzir o delay e jitter1 para as aplicações de tempo real; que de fato a habilitação de QoS Intserv provê classificação e faz diferenciação dos tráfegos, e que o CODEC G729 apresenta melhor adequação em lidar com aplicações VoIP em routers2 CISCO, disponível em CRT (Centro de referência Tecnológica) de uma LOP.

Financial liberalization, bank crises and growth: Assessing the links

This paper studies the effects of financial liberalization and banking crises on growth. It shows that financial liberalization spurs on average economic growth. Banking crises are harmful for growth, but to a lesser extent in countries with open financial systems and good institutions. The positive effect of financial liberalization is robust to different definitions. While the removal of capital account restrictions is effective by increasing financial depth, equity market liberalization affects growth directly. The empirical analysis is performed through GMM dynamic panel data estimations on a panel of 90 countries observed in the period 1975-1999.

Heterotrimeric Go protein links Wnt-Frizzled signaling with ankyrins to regulate the neuronal microtubule cytoskeleton.

Drosophila neuromuscular junctions (NMJs) represent a powerful model system with which to study glutamatergic synapse formation and remodeling. Several proteins have been implicated in these processes, including components of canonical Wingless (Drosophila Wnt1) signaling and the giant isoforms of the membrane-cytoskeleton linker Ankyrin 2, but possible interconnections and cooperation between these proteins were unknown. Here, we demonstrate that the heterotrimeric G protein Go functions as a transducer of Wingless-Frizzled 2 signaling in the synapse. We identify Ankyrin 2 as a target of Go signaling required for NMJ formation. Moreover, the Go-ankyrin interaction is conserved in the mammalian neurite outgrowth pathway. Without ankyrins, a major switch in the Go-induced neuronal cytoskeleton program is observed, from microtubule-dependent neurite outgrowth to actin-dependent lamellopodial induction. These findings describe a novel mechanism regulating the microtubule cytoskeleton in the nervous system. Our work in Drosophila and mammalian cells suggests that this mechanism might be generally applicable in nervous system development and function.