Rotatin is a novel gene required for axial rotation and left- right specification in mouse embryos

The genetic cascade that governs left-right (L-R) specification is starting to be elucidated. In the mouse, the lateral asymmetry of the body axis is revealed first by the asymmetric expression of nodal, lefry2 and pitx2 in the left lateral plate mesoderm of the neurulating embryo. Here we describe a novel gene, rotatin, essential for the correct expression of the key L-R specification genes nodal, lefty and Pitx2. Embryos deficient in rotatin show also randomized heart looping and delayed neural tube closure, and fail to undergo the critical morphogenetic step of axial rotation. The amino acid sequence deduced from the cDNA is predicted to contain at least three transmembrane domains. Our results show a novel key player in the genetic cascade that determines L-R specification, and suggest a causal link between this process and axial rotation. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved

Transcription factors Sp1 and Sp4 regulate TRPV1 gene expression in rat sensory neurons

<p>Abstract</p> <p>Background</p> <p>The capsaicin receptor, transient receptor potential vanilloid type -1 (TRPV1) directs complex roles in signal transduction including the detection of noxious stimuli arising from cellular injury and inflammation. Under pathophysiologic conditions, TRPV1 mRNA and receptor protein expression are elevated in dorsal root ganglion (DRG) neurons for weeks to months and is associated with hyperalgesia. Building on our previous isolation of a promoter system for the rat TRPV1 gene, we investigated the proximal TRPV1 P2-promoter by first identifying candidate Sp1-like transcription factors bound <it>in vivo </it>to the P2-promoter using chromatin immunoprecipitation (ChIP) assay. We then performed deletion analysis of GC-box binding sites, and quantified promoter activity under conditions of Sp1 / Sp4 over-expression versus inhibition/knockdown. mRNA encoding Sp1, Sp4 and TRPV1 were quantified by qRT-PCR under conditions of Sp1/Sp4 over-expression or siRNA mediated knockdown in cultured DRG neurons.</p> <p>Results</p> <p>Using ChIP analysis of DRG tissue, we demonstrated that Sp1 and Sp4 are bound to the candidate GC-box site region within the endogenous TRPV1 P2-promoter. Deletion of GC-box "a" or "a + b" within the P2- promoter resulted in a complete loss of transcriptional activity indicating that GC-box "a" was the critical site for promoter activation. Co-transfection of Sp1 increased P2-promoter activity in cultured DRG neurons whereas mithramycin-a, an inhibitor of Sp1-like function, dose dependently blocked NGF and Sp1-dependent promoter activity in PC12 cells. Co-transfection of siRNA directed against Sp1 or Sp4 decreased promoter activity in DRG neurons and NGF treated PC12 cells. Finally, electroporation of Sp1 or Sp4 cDNA into cultures of DRG neurons directed an increase in Sp1/Sp4 mRNA and importantly an increase in TRPV1 mRNA. Conversely, combined si-RNA directed knockdown of Sp1/Sp4 resulted in a decrease in TRPV1 mRNA.</p> <p>Conclusion</p> <p>Based on these studies, we now propose a model of TRPV1 expression that is dependent on Sp1-like transcription factors with Sp4 playing a predominant role in activating TRPV1 RNA transcription in DRG neurons. Given that increases of TRPV1 expression have been implicated in a wide range of pathophysiologic states including persistent painful conditions, blockade of Sp1-like transcription factors represents a novel direction in therapeutic strategies.</p

Economic impact to shipping industry : Economic impact to shipping industry considering Maritime Spatial Planning and green routes in pilot case studies

In this project, three case studies are considered in order to examine the economic impact of the implementation of MSP when considering environmental impact of the shipping industry. Specific characteristics and limitations of areas in the Greek Sea, the Balearic Sea and the Baltic Sea are evaluated with respect to their economic effects on the maritime transport domain. The purpose of the above is to evaluate the economic impacts and risk implications of different scenarios and particularly: The economic impact of vessel traffic rerouting and/or reducing the speed in order to reduce the probability of vessel strikes or other negative impact to endangered marine species. Analysis and treatment of costs (constraints and penalties) from unexpected delays, in addition to the additional transit time cost. Estimation of the direct and indirect economic impact on the shipping industry and the effects of potential port call dislocation for the implementation of the proposed management options (e.g. speed deceleration or ship rerouting).https://commons.wmu.se/monalisa2/1001/thumbnail.jp

A conserved function of the zinc finger transcription factor Sp8/9 in allometric appendage growth in the milkweed bug Oncopeltus fasciatus

The genes encoding the closely related zinc finger transcription factors Buttonhead (Btd) and D-Sp1 are expressed in the developing limb primordia of Drosophila melanogaster and are required for normal growth of the legs. The D-Sp1 homolog of the red flour beetle Tribolium castaneum, Sp8 (appropriately termed Sp8/9), is also required for the proper growth of the leg segments. Here we report on the isolation and functional study of the Sp8/9 gene from the milkweed bug Oncopeltus fasciatus. We show that Sp8/9 is expressed in the developing appendages throughout development and that the downregulation of Sp8/9 via RNAi leads to antennae, rostrum, and legs with shortened and fused segments. This supports a conserved role of Sp8/9 in allometric leg segment growth. However, all leg segments including the claws are present and the expression of the leg genes Distal-less, dachshund, and homothorax are proportionally normal, thus providing no evidence for a role of Sp8/9 in appendage specification

Atmospheric Muon Flux at Sea Level, Underground, and Underwater

The vertical sea-level muon spectrum at energies above 1 GeV and the underground/underwater muon intensities at depths up to 18 km w.e. are calculated. The results are particularly collated with a great body of the ground-level, underground, and underwater muon data. In the hadron-cascade calculations, the growth with energy of inelastic cross sections and pion, kaon, and nucleon generation in pion-nucleus collisions are taken into account. For evaluating the prompt muon contribution to the muon flux, we apply two phenomenological approaches to the charm production problem: the recombination quark-parton model and the quark-gluon string model. To solve the muon transport equation at large depths of homogeneous medium, a semi-analytical method is used. The simple fitting formulas describing our numerical results are given. Our analysis shows that, at depths up to 6-7 km w. e., essentially all underground data on the muon intensity correlate with each other and with predicted depth-intensity relation for conventional muons to within 10%. However, the high-energy sea-level data as well as the data at large depths are contradictory and cannot be quantitatively decribed by a single nuclear-cascade model.Comment: 47 pages, REVTeX, 15 EPS figures included; recent experimental data and references added, typos correcte

The Association between Mental Health and Violence among a Nationally Representative Sample of College Students from the United States

Objectives Recent violent attacks on college campuses in the United States have sparked discussions regarding the prevalence of psychiatric disorders and the perpetration of violence among college students. While previous studies have examined the potential association between mental health problems and violent behavior, the overall pattern of findings flowing from this literature remain mixed and no previous studies have examined such associations among college students. Methods The current study makes use of a nationally representative sample of 3,929 college students from the National Epidemiologic Study on Alcohol and Related Conditions (NESARC) to examine the prevalence of seven violent behaviors and 19 psychiatric disorder diagnoses tapping mood, anxiety, personality, and substance use disorders. Associations between individual and composite psychiatric disorder diagnoses and violent behaviors were also examined. Additional analyses were adjusted for the comorbidity of multiple psychiatric diagnoses. Results The results revealed that college students were less likely to have engaged in violent behavior relative to the non-student sample, but a substantial portion of college students had engaged in violent behavior. Age- and sex-standardized prevalence rates indicated that more than 21% of college students reported at least one violent act. In addition, more than 36% of college students had at least one diagnosable psychiatric disorder. Finally, the prevalence of one or more psychiatric disorders significantly increased the odds of violent behavior within the college student sample. Conclusions These findings indicate that violence and psychiatric disorders are prevalent on college campuses in the United States, though perhaps less so than in the general population. In addition, college students who have diagnosable psychiatric disorders are significantly more likely to engage in various forms of violent behavior

New limit on neutrinoless double β decay in ^(136)Xe with a time projection chamber

A xenon time projection chamber with an active volume of 207 L has been built to study neutrinoless double β decay in ^(136)Xe. Data were taken in the Gotthard Underground Laboratory, with 5 atm of xenon enriched to 62.5% in ^(136)Xe. From 3380 h of data, no evidence has been found for the 0ν 0^(+)→0^(+) transition. Half-life limits of T_(1/2)^(0ν)>2.5(4.9)×10^(23) yr in the mass-mechanism mode and T_(1/2)^(0ν)>1.7(3.2)×10^(23) yr in the right-handed-current mode, at the 90(68)% C.L., were derived. An upper limit for the Majorana neutrino mass parameter was deduced

A Re-Evaluation of the nuclear Structure Function Ratios for D, He, Li, C and Ca

We present a re-evaluation of the structure function ratios F2(He)/F2(D), F2(C)/F2(D) and F2(Ca)/F2(D) measured in deep inelastic muon-nucleus scattering at an incident muon momentum of 200 GeV. We also present the ratios F2(C)/F2(Li), F2(Ca)/F2(Li) and F2(Ca)/F2(C) measured at 90 GeV. The results are based on data already published by NMC; the main difference in the analysis is a correction for the masses of the deuterium targets and an improvement in the radiative corrections. The kinematic range covered is 0.0035 < x < 0.65, 0.5 < Q^2 <90 GeV^2 for the He/D, C/D and Ca/D data and 0.0085 < x < 0.6, 0.84 < Q^2 < 17 GeV^2 for the Li/C/Ca ones.Comment: 6 pages, Latex, 3 figures as uuencoded compressed tar file included at the end, in case of problems contact [email protected] (Antje Bruell

E-Cadherin Acts as a Regulator of Transcripts Associated with a Wide Range of Cellular Processes in Mouse Embryonic Stem Cells

We have recently shown that expression of the cell adhesion molecule E-cadherin is required for LIF-dependent pluripotency of mouse embryonic stem (ES) cells.In this study, we have assessed global transcript expression in E-cadherin null (Ecad-/-) ES cells cultured in either the presence or absence of LIF and compared these to the parental cell line wtD3.We show that LIF has little effect on the transcript profile of Ecad-/- ES cells, with statistically significant transcript alterations observed only for Sp8 and Stat3. Comparison of Ecad-/- and wtD3 ES cells cultured in LIF demonstrated significant alterations in the transcript profile, with effects not only confined to cell adhesion and motility but also affecting, for example, primary metabolic processes, catabolism and genes associated with apoptosis. Ecad-/- ES cells share similar, although not identical, gene expression profiles to epiblast-derived pluripotent stem cells, suggesting that E-cadherin expression may inhibit inner cell mass to epiblast transition. We further show that Ecad-/- ES cells maintain a functional β-catenin pool that is able to induce β-catenin/TCF-mediated transactivation but, contrary to previous findings, do not display endogenous β-catenin/TCF-mediated transactivation. We conclude that loss of E-cadherin in mouse ES cells leads to significant transcript alterations independently of β-catenin/TCF transactivation

Search for neutrinoless double-beta decay in 136-Xe with a time projection chamber

A xenon time projection chamber (TPC) with an active volume of 180 liters has been built to study neutrinoless double-beta decay in Xe-136. The experiment was performed in the Gotthard Underground Laboratory, with 5 atm of xenon enriched to 62.5% in Xe-136. The experimental details, background considerations, detector performance, and data analysis are discussed. From 6830 h of data, no evidence has been found for the 0nu 0+-->0+ transition. Half-life limits of T1/2(0nu) > 3.4(6.4) X 10^(23) yr in the mass mechanism mode, and T1/2(0nu) > 2.6(4.9) X 10^23 yr in the right-handed currents mode, at the 90(68)% C.L., were derived, corresponding to an upper limit on the Majorana neutrino mass parameter [m(nu)] of about 2.8 eV. Limits on two-neutrino double-beta decay of T1/2(2nu) /2 > 2. 1 X 10^(20) yr, and on neutrinoless double-beta decay with Majoron emission of T1/2(0nuchi) > 4.9 X 10^(21) yr, both at 90% C.L., were also derived. Accordingly, a limit on the effective Majoron-neutrino coupling parameter of [g(M)] < 2.4 X 10^(-4) was deduced