Neurotrophin-Induced Transport of a β-Actin mRNP Complex Increases β-Actin Levels and Stimulates Growth Cone Motility

AbstractNeurotrophin regulation of actin-dependent changes in growth cone motility may depend on the signaling of β-actin mRNA transport. Formation of an RNP complex between the β-actin mRNA zipcode sequence and Zipcode Binding Protein 1 (ZBP1) was required for its localization to growth cones. Antisense oligonucleotides to the zipcode inhibited formation of this RNP complex in vitro and the neurotrophin-induced localization of β-actin mRNA and ZBP1 granules. Live cell imaging of neurons transfected with EGFP-ZBP1 revealed fast, bidirectional movements of granules in neurites that were inhibited by antisense treatment, as visualized by FRAP analysis. NT-3 stimulation of β-actin protein localization was dependent on the 3′UTR and inhibited by antisense treatment. Growth cones exhibited impaired motility in the presense of antisense. These results suggest a novel mechanism to influence growth cone dynamics involving the regulated transport of mRNA

Prenatal phthalate exposures and child temperament at 12 and 24 months

Introduction Gestational phthalate exposures have been adversely associated with attention, externalizing, and internalizing behaviors in childhood. Early childhood temperament may be a marker of later behavioral patterns. We therefore sought to determine whether gestational phthalate exposures were associated with infant and toddler temperament. Methods The Mount Sinai Children's Environmental Health Study is a prospective cohort study of children born between May 1998 and July 2001 in New York City (N = 404). Phthalate metabolites were measured in spot urine samples collected from pregnant women in their third trimester. Child temperament was assessed by parental report at 12-months using the Infant Behavior Questionnaire (IBQ) (N = 204) and at 24-months using the Toddler Behavior Assessment Questionnaire (TBAQ) (N = 279). We used multiple linear regression to evaluate associations between urinary phthalate metabolites and eleven temperament domains. Results Phthalate biomarker concentrations were weakly associated with lower gross motor activity levels as well as higher duration of orienting at the 12-month assessment. Mono(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP) and the sum of metabolites of di(2-ethylhexyl) phthalate (∑DEHP) were associated with lower levels of smiling and laughing at 12 months. At 24-months, social fear and lower pleasure was linked to higher concentrations of MCPP and MBzP, and higher ∑DEHP was weakly associated with increased anger levels at 24-months. Conclusions Though we observed some weak associations between biomarkers of prenatal exposure to phthalates and temperament at 12- and 24-months, overall phthalates biomarkers were not strongly associated with alterations in temperament

ω−ρ\omega-\rho Mixing and the ω→ππγ\omega\to\pi\pi\gamma Decay

We reexamine the $\omega \to \pi^{0} \pi^{0} \gamma$ decay, adding the effect of $\omega-\rho$ mixing to the amplitude calculated with the aid of chiral perturbation theory and vector meson dominance. We predict the neutral decay to occur with a width of $\Gamma($\omega \to \pi^{0} \pi^{0} \gamma $) =(390\pm96) {\rm eV}$ and also analyze the effect of the $\omega-\rho$ mixing on the $\Gamma($\omega \to \pi^{0} \pi^{0} \gamma $)/ \Gamma($\omega \to \pi^{+} \pi^{-} \gamma $)$ ratio. Several remarks on the effect of $\omega-\rho$ mixing on certain radiative decays of vector mesons are presented.Comment: 10 pages, LaTeX, 1 ps-figure. Submitted to Phys. Rev.

Upper critical field for underdoped high-T_c superconductors. Pseudogap and stripe--phase

We investigate the upper critical field in a stripe--phase and in the presence of a phenomenological pseudogap. Our results indicate that the formation of stripes affects the Landau orbits and results in an enhancement of $H_{c2}$. On the other hand, phenomenologically introduced pseudogap leads to a reduction of the upper critical field. This effect is of particular importance when the magnitude of the gap is of the order of the superconducting transition temperature. We have found that a suppression of the upper critical field takes place also for the gap that originates from the charge--density waves.Comment: 7 pages, 5 figure

Stability of metallic stripes in the extended one-band Hubbard model

Based on an unrestricted Gutzwiller approximation (GA) we investigate the stripe orientation and periodicity in an extended one-band Hubbard model. A negative ratio between next-nearest and nearest neighbor hopping t'/t, as appropriate for cuprates, favors partially filled (metallic) stripes for both vertical and diagonal configurations. At around optimal doping diagonal stripes, site centered (SC) and bond centered (BC) vertical stripes become degenerate suggesting strong lateral and orientational fluctuations. We find that within the GA the resulting phase diagram is in agreement with experiment whereas it is not in the Hartree-Fock approximation due to a strong overestimation of the stripe filling. Results are in agreement with previous calculations within the three-band Hubbard model but with the role of SC and BC stripes interchanged.Comment: 10 pages, 8 figure

Final State Interactions in the Ds+ --> omega pi+ and Ds+ --> rho0 pi+ Decays

We investigate the decay mechanisms in the Ds+ --> omega pi+ and Ds+ --> rho0 pi+ transitions. The naive factorization ansatz predicts vanishing amplitude for the Ds+ --> omega pi+ decay, while the Ds+ --> rho0 pi+ decay amplitude does have an annihilation contribution also in this limit. Both decays can proceed through intermediate states of hidden strangeness, e.g. K, K*, which we estimate in this paper. These contributions can explain the experimental value for the Ds+ --> omega pi+ decay rate, which no longer can be viewed as a clean signature of the annihilation decay of Ds+. The combination of the \pi(1300) pole dominated annihilation contribution and the internal K, K* exchange can saturate present experimental upper bound on Ds+ --> rho0 pi+ decay rate, which is therefore expected to be within the experimental reach. Finally, the proposed mechanism of hidden strangeness FSI constitutes only a small correction to the Cabibbo allowed decay rates Ds--> K K*, phi pi, which are well described already in the factorization approximation.Comment: 12 pages, 3 figure

Two shades of Green? The electorates of GreenLeft and the Party for the Animals

The Netherlands has two electorally significant parties that might be considered to be part of the Green' family: GreenLeft and the Party for the Animals. These two parties appeal to different niches of the Green electorate, identified on the basis of issue dimensions, demographics, and their trust in government. GreenLeft tends to attract voters from the traditional Green niche: those with egalitarian, cosmopolitan, environmentalist, and libertarian values. The Party for the Animals attracts another type of Green voter: significantly less cosmopolitan and evincing lower levels of political trust.</p

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Early- Onset Stroke and Vasculopathy Associated with Mutations in ADA2

Adenosine deaminase 2 (ADA2) is an enzyme involved in purine metabolism and a growth factor that influences the development of endothelial cells and leukocytes. This study shows that defects in ADA2 cause recurrent fevers, vascular pathologic features, and mild immunodeficiency. Patients with autoinflammatory disease sometimes present with clinical findings that encompass multiple organ systems.(1) Three unrelated children presented to the National Institutes of Health (NIH) Clinical Center with intermittent fevers, recurrent lacunar strokes, elevated levels of acute-phase reactants, livedoid rash, hepatosplenomegaly, and hypogammaglobulinemia. Collectively, these findings do not easily fit with any of the known inherited autoinflammatory diseases. Hereditary or acquired vascular disorders can have protean manifestations yet be caused by mutations in a single gene. Diseases such as the Aicardi-Goutieres syndrome,(2),(3) polypoidal choroidal vasculopathy,(4) sickle cell anemia,(5) livedoid vasculopathy,(6) and the small-vessel vasculitides(7),(8) are examples of systemic ...</p

Recommendations for clinical interpretation of variants found in non-coding regions of the genome

Background The majority of clinical genetic testing focuses almost exclusively on regions of the genome that directly encode proteins. The important role of variants in non-coding regions in penetrant disease is, however, increasingly being demonstrated, and the use of whole genome sequencing in clinical diagnostic settings is rising across a large range of genetic disorders. Despite this, there is no existing guidance on how current guidelines designed primarily for variants in protein-coding regions should be adapted for variants identified in other genomic contexts. Methods We convened a panel of nine clinical and research scientists with wide-ranging expertise in clinical variant interpretation, with specific experience in variants within non-coding regions. This panel discussed and refined an initial draft of the guidelines which were then extensively tested and reviewed by external groups. Results We discuss considerations specifically for variants in non-coding regions of the genome. We outline how to define candidate regulatory elements, highlight examples of mechanisms through which non-coding region variants can lead to penetrant monogenic disease, and outline how existing guidelines can be adapted for the interpretation of these variants. Conclusions These recommendations aim to increase the number and range of non-coding region variants that can be clinically interpreted, which, together with a compatible phenotype, can lead to new diagnoses and catalyse the discovery of novel disease mechanisms