Follistatin-like 3 (FSTL3) mediated silencing of transforming growth factor (TGF ) signaling is essential for testicular aging and regulating testis size

Follistatin-like 3 (FSTL3) is a glycoprotein that binds and inhibits the action of TGFβ ligands such as activin. The roles played by FSTL3 and activin signaling in organ development and homeostasis are not fully understood. The authors show mice deficient in FSTL3 develop markedly enlarged testes that are also delayed in their age-related regression. These FSTL3 knockout mice exhibit increased Sertoli cell numbers, allowing for increased spermatogenesis but otherwise showing normal testicular function. The data show that FSTL3 deletion leads to increased AKT signaling and SIRT1 expression in the testis. This demonstrates a cross-talk between TGFβ ligand and AKT signaling and leads to a potential mechanism for increased cellular survival and antiaging. The findings identify crucial roles for FSTL3 in limiting testis organ size and promoting age-related testicular regression

Polarization transfer in the 4^{4}He(e⃗,e′p⃗3(\vec{e},e' \vec{p}^{3}H reaction

Polarization transfer in the 4He(e,e'p)3H reaction at a Q^2 of 0.4 (GeV/c)^2 was measured at the Mainz Microtron MAMI. The ratio of the transverse to the longitudinal polarization components of the ejected protons was compared with the same ratio for elastic ep scattering. The results are consistent with a recent fully relativistic calculation which includes a predicted medium modification of the proton form factor based on a quark-meson coupling model.Comment: 5 pages, Latex, 2 postscript figures, submitted to Physics Letters

An inclusive search for free quarks at PEP

Abstract We report the results of a search for fractionally charged particles in e + e − reactions at a center of mass energy of 29 GeV. We find no evidence for such particles and present upper limitts on R q = σ q q X/σ μμ for change 1 3 e and 2 3 e which range from 1 to 8 × 10 −2 for mass up to 12 GeV/ c 2

Search for fractionally charged particles in cosmic rays at large zenith angles

We have performed a single-particle search for fractional charge in cosmic rays having residual ranges at sea level >250 g/cm/sup 2/ concrete and zenith angles between 45/sup 0/ and 90/sup 0/. The detector is a hodoscope of 24 layers of plastic scintillator, eight layers of multiwire proportional chambers, and two layers of lucite Cherenkov counters. The acceptance of the instrument is 4.0 x 10/sup 3/ cm/sup 2/sr. An analysis of 3.5 x 10/sup 6/ triggers during a running time of 8 x 10/sup 5/ sec yields no particles with charge Q = (1/3) or Q = (2/3) and velocities greater than roughly-equal0.1c. We deduce an upper limit on the flux of fractionally charged particles of 8.5 x 10/sup -10/ (cm/sup 2/sr sec)/sup -1/ for relativistic Q = (1/3) and 7.6 x 10/sup -10/ (cm/sup 2/sr sec)/sup -1/ for Q = (2/3)

Planeamiento territorial sostenible: un reto para el futuro de nuestras sociedades; criterios aplicados

In a large part of the 17 sustainable development objectives set as goals for humanity by the UN, sustainability can be glimpsed. As a result of the dominant socio-productive model, the only way to head towards more sustainable territories that allow achieving and maintaining the well-being of the world's population is to bear in mind the need to properly plan territorial development. This work reflects on this need and takes a step forward in the definition of the main criteria to achieve territorial sustainability at regional and local scales

Human PAPS Synthase Isoforms Are Dynamically Regulated Enzymes with Access to Nucleus and Cytoplasm

In higher eukaryotes, PAPS synthases are the only enzymes producing the essential sulphate-donor 3′-phospho-adenosine-5′-phosphosulphate (PAPS). Recently, PAPS synthases have been associated with several genetic diseases and retroviral infection. To improve our understanding of their pathobiological functions, we analysed the intracellular localisation of the two human PAPS synthases, PAPSS1 and PAPSS2. For both enzymes, we observed pronounced heterogeneity in their subcellular localisation. PAPSS1 was predominantly nuclear, whereas PAPSS2 localised mainly within the cytoplasm. Treatment with the nuclear export inhibitor leptomycin B had little effect on their localisation. However, a mutagenesis screen revealed an Arg-Arg motif at the kinase interface exhibiting export activity. Notably, both isoforms contain a conserved N-terminal basic Lys-Lys-Xaa-Lys motif indispensable for their nuclear localisation. This nuclear localisation signal was more efficient in PAPSS1 than in PAPSS2. The activities of the identified localisation signals were confirmed by microinjection studies. Collectively, we describe unusual localisation signals of both PAPS synthase isoforms, mobile enzymes capable of executing their function in the cytoplasm as well as in the nucleus

Hypoxia Reduces Arylsulfatase B Activity and Silencing Arylsulfatase B Replicates and Mediates the Effects of Hypoxia

This report presents evidence of 1) a role for arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) in mediating intracellular oxygen signaling; 2) replication between the effects of ARSB silencing and hypoxia on sulfated glycosaminoglycan content, cellular redox status, and expression of hypoxia-associated genes; and 3) a mechanism whereby changes in chondroitin-4-sulfation that follow either hypoxia or ARSB silencing can induce transcriptional changes through galectin-3. ARSB removes 4-sulfate groups from the non-reducing end of chondroitin-4-sulfate and dermatan sulfate and is required for their degradation. For activity, ARSB requires modification of a critical cysteine residue by the formylglycine generating enzyme and by molecular oxygen. When primary human bronchial and human colonic epithelial cells were exposed to 10% O2×1 h, ARSB activity declined by ∼41% and ∼30% from baseline, as nuclear hypoxia inducible factor (HIF)-1α increased by ∼53% and ∼37%. When ARSB was silenced, nuclear HIF-1α increased by ∼81% and ∼61% from baseline, and mRNA expression increased to 3.73 (±0.34) times baseline. Inversely, ARSB overexpression reduced nuclear HIF-1α by ∼37% and ∼54% from baseline in the epithelial cells. Hypoxia, like ARSB silencing, significantly increased the total cellular sulfated glycosaminoglycans and chondroitin-4-sulfate (C4S) content. Both hypoxia and ARSB silencing had similar effects on the cellular redox status and on mRNA expression of hypoxia-associated genes. Transcriptional effects of both ARSB silencing and hypoxia may be mediated by reduction in galectin-3 binding to more highly sulfated C4S, since the galectin-3 that co-immunoprecipitated with C4S declined and the nuclear galectin-3 increased following ARSB knockdown and hypoxia

Transcriptome Analysis Reveals Strain-Specific and Conserved Stemness Genes in Schmidtea mediterranea

The planarian Schmidtea mediterranea is a powerful model organism for studying stem cell biology due to its extraordinary regenerative ability mediated by neoblasts, a population of adult somatic stem cells. Elucidation of the S. mediterranea transcriptome and the dynamics of transcript expression will increase our understanding of the gene regulatory programs that regulate stem cell function and differentiation. Here, we have used RNA-Seq to characterize the S. mediterranea transcriptome in sexual and asexual animals and in purified neoblast and differentiated cell populations. Our analysis identified many uncharacterized genes, transcripts, and alternatively spliced isoforms that are differentially expressed in a strain or cell type-specific manner. Transcriptome profiling of purified neoblasts and differentiated cells identified neoblast-enriched transcripts, many of which likely play important roles in regeneration and stem cell function. Strikingly, many of the neoblast-enriched genes are orthologs of genes whose expression is enriched in human embryonic stem cells, suggesting that a core set of genes that regulate stem cell function are conserved across metazoan species

Search For Exotic Tau-decays

The Crystal Ball detector at the Doris II storage ring at DESY was used to search for the exotic decay processes tau -> e gamma, tau -> e pi0, tau -> e eta. No signal was observed. We obtained the following 90% CL upper limits on the branching fractions:B(tau -> e gamma)< 2.0x10^(-4),B(tau -> e pi0) < 1.4x10^(-4),B(tau -> e eta) < 2.4x10^(-4)