Specific organization of the negative response elements for retinoic acid and thyroid hormone receptors in keratin gene family

Retinoic acid and thyroid hormone are important regulators of epidermal growth, differentiation, and homeostasis, Retinoic acid is extensively used in the treatment of many epidermal disorders ranging from wrinkles to skin cancers. Retinoic acid and thyroid hormone directly control the transcription of differentiation-specific genes including keratins. Their effect is mediated through nuclear receptors RAR and T3R. We have previously identified the response element in the K14 gene, K14RARE/TRE, to which these receptors bind, and found that it consists of a cluster of five half-sites with variable spacing and orientation. To determine whether this specific structure is found in other keratin genes, we have mapped and analyzed the RARE/TRE elements in three additional epidermal keratin genes: K5, K6, and K17. We used three different approaches to identify these elements: co-transfection of promoter deletion constructs, gel-shift assays, and site-specific mutagenesis. We localized the RARE/TRE elements relatively close to the TATA box in all three promoters. All three RARE/TRE elements have a similar structural organization: they consist of clusters of 3-6 half-sites with variable spacing and orientation. This means that the clustered structure of the RARE/TREs is a common characteristic for keratin genes. RARE and TRE in the K5 promoter are adjacent to each other whereas in the K17 promoter they overlap. All three keratin REs bind specifically both RAR and T3R in gel-shift assays. Interestingly, addition of ligand to the receptor changes the binding pattern of the T3R from homodimer to monomer, reflecting the change in regulation from induction to inhibition

Realistic Standard Model Fermion Mass Relations in Generalized Minimal Supergravity (GmSUGRA)

Grand Unified Theories (GUTs) usually predict wrong Standard Model (SM) fermion mass relation m_e/m_{\mu} = m_d/m_s toward low energies. To solve this problem, we consider the Generalized Minimal Supergravity (GmSUGRA) models, which are GUTs with gravity mediated supersymmetry breaking and higher dimensional operators. Introducing non-renormalizable terms in the super- and K\"ahler potentials, we can obtain the correct SM fermion mass relations in the SU(5) model with GUT Higgs fields in the {\bf 24} and {\bf 75} representations, and in the SO(10) model. In the latter case the gauge symmetry is broken down to SU(3)_C X SU(2)_L X SU(2)_R X U(1)_{B-L}, to flipped SU(5)X U(1)_X, or to SU(3)_C X SU(2)_L X U(1)_1 X U(1)_2. Especially, for the first time we generate the realistic SM fermion mass relation in GUTs by considering the high-dimensional operators in the K\"ahler potential.Comment: JHEP style, 29 pages, no figure,references adde

First Report of 13 Species of Culicoides (Diptera: Ceratopogonidae) in Mainland Portugal and Azores by Morphological and Molecular Characterization

The genus Culicoides (Diptera: Ceratopogonidae) contains important vectors of animal and human diseases, including bluetongue, African horse sickness and filariosis. A major outbreak of bluetongue occurred in mainland Portugal in 2004, forty eight years after the last recorded case. A national Entomological Surveillance Plan was initiated in mainland Portugal, Azores and the Madeira archipelagos in 2005 in order to better understand the disease and facilitate policy decisions. During the survey, the most prevalent Culicoides species in mainland Portugal was C. imicola (75.3%) and species belonging to the Obsoletus group (6.5%). The latter were the most prevalent in Azores archipelago, accounting for 96.7% of the total species identified. The Obsoletus group was further characterized by multiplex Polymerase Chain Reaction to species level showing that only two species of this group were present: C. obsoletus sensu strictu (69.6%) and C. scoticus (30.4%). Nine species of Culicoides were detected for the first time in mainland Portugal: C. alazanicus, C. bahrainensis, C. deltus, C. lupicaris, C. picturatus, C. santonicus, C. semimaculatus, C. simulator and C. subfagineus. In the Azores, C. newsteadi and C. circumscriptus were identified for the first time from some islands, and bluetongue vectors belonging to the Obsoletus group (C. obsoletus and C. scoticus) were found to be widespread

Probing non-standard interactions at Daya Bay

In this article we consider the presence of neutrino non-standard interactions (NSI) in the production and detection processes of reactor antineutrinos at the Daya Bay experiment. We report for the first time, the new constraints on the flavor non-universal and flavor universal charged-current NSI parameters, estimated using the currently released 621 days of Daya Bay data. New limits are placed assuming that the new physics effects are just inverse of each other in the production and detection processes. With this special choice of the NSI parameters, we observe a shift in the oscillation amplitude without distorting the L/E pattern of the oscillation probability. This shift in the depth of the oscillation dip can be caused by the NSI parameters as well as by theta(13), making it quite difficult to disentangle the NSI effects from the standard oscillations. We explore the correlations between the NSI parameters and theta(13) that may lead to significant deviations in the reported value of the reactor mixing angle with the help of iso-probability surface plots. Finally, we present the limits on electron, muon/tau, and flavor universal (FU) NSI couplings with and without considering the uncertainty in the normalization of the total event rates. Assuming a perfect knowledge of the event rates normalization, we find strong upper bounds similar to 0.1% for the electron and FU cases improving the present limits by one order of magnitude. However, for a conservative error of 5% in the total normalization, these constraints are relaxed by almost one order of magnitude

Chatter that Matters: Word-of-Mouth Marketing of Selected Micro Businesses and Small and Medium Enterprises in Malolos City, Bulacan

The study quantified the usage of and range of word-of-mouth (WOM) marketing, and analyzed the present state and satisfaction with WOM marketing tactics of selected micro businesses, small and medium enterprises in Malolos City, Bulacan. Purposive and convenience sampling were employed on marketers and owners who were available and who were willing to participate in the study using structured interview questions. 125 companies situated only in Malolos City proper and proximate places were selected

Observation of a J^PC = 1-+ exotic resonance in diffractive dissociation of 190 GeV/c pi- into pi- pi- pi+

The COMPASS experiment at the CERN SPS has studied the diffractive dissociation of negative pions into the pi- pi- pi+ final state using a 190 GeV/c pion beam hitting a lead target. A partial wave analysis has been performed on a sample of 420000 events taken at values of the squared 4-momentum transfer t' between 0.1 and 1 GeV^2/c^2. The well-known resonances a1(1260), a2(1320), and pi2(1670) are clearly observed. In addition, the data show a significant natural parity exchange production of a resonance with spin-exotic quantum numbers J^PC = 1-+ at 1.66 GeV/c^2 decaying to rho pi. The resonant nature of this wave is evident from the mass-dependent phase differences to the J^PC = 2-+ and 1++ waves. From a mass-dependent fit a resonance mass of 1660 +- 10+0-64 MeV/c^2 and a width of 269+-21+42-64 MeV/c^2 is deduced.Comment: 7 page, 3 figures; version 2 gives some more details, data unchanged; version 3 updated authors, text shortened, data unchange

BODE index versus GOLD classification for explaining anxious and depressive symptoms in patients with COPD – a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Anxiety and depression are common and treatable risk factors for re-hospitalisation and death in patients with COPD. The degree of lung function impairment does not sufficiently explain anxiety and depression. The BODE index allows a functional classification of COPD beyond FEV₁. The aim of this cross-sectional study was (1) to test whether the BODE index is superior to the GOLD classification for explaining anxious and depressive symptoms; and (2) to assess which components of the BODE index are associated with these psychological aspects of COPD.</p> <p>Methods</p> <p>COPD was classified according to the GOLD stages based on FEV_1%predictedin 122 stable patients with COPD. An additional four stage classification was constructed based on the quartiles of the BODE index. The hospital anxiety and depression scale was used to assess anxious and depressive symptoms.</p> <p>Results</p> <p>The overall prevalence of anxious and depressive symptoms was 49% and 52%, respectively. The prevalence of anxious symptoms increased with increasing BODE stages but not with increasing GOLD stages. The prevalence of depressive symptoms increased with both increasing GOLD and BODE stages. The BODE index was superior to FEV_1%predictedfor explaining anxious and depressive symptoms. Anxious symptoms were explained by dyspnoea. Depressive symptoms were explained by both dyspnoea and reduced exercise capacity.</p> <p>Conclusion</p> <p>The BODE index is superior to the GOLD classification for explaining anxious and depressive symptoms in COPD patients. These psychological consequences of the disease may play a role in future classification systems of COPD.</p

The search for transient astrophysical neutrino emission with IceCube-DeepCore

We present the results of a search for astrophysical sources of brief transient neutrino emission using IceCube and DeepCore data acquired between 2012 May 15 and 2013 April 30. While the search methods employed in this analysis are similar to those used in previous IceCube point source searches, the data set being examined consists of a sample of predominantly sub-TeV muon-neutrinos from the Northern Sky (-5 degrees < delta < 90 degrees) obtained through a novel event selection method. This search represents a first attempt by IceCube to identify astrophysical neutrino sources in this relatively unexplored energy range. The reconstructed direction and time of arrival of neutrino events are used to search for any significant self-correlation in the data set. The data revealed no significant source of transient neutrino emission. This result has been used to construct limits at timescales ranging from roughly 1 s to 10 days for generic soft-spectra transients. We also present limits on a specific model of neutrino emission from soft jets in core-collapse supernovae

An in vitro model of early anteroposterior organization during human development.

The body plan of the mammalian embryo is shaped through the process of gastrulation, an early developmental event that transforms an isotropic group of cells into an ensemble of tissues that is ordered with reference to three orthogonal axes1. Although model organisms have provided much insight into this process, we know very little about gastrulation in humans, owing to the difficulty of obtaining embryos at such early stages of development and the ethical and technical restrictions that limit the feasibility of observing gastrulation ex vivo2. Here we show that human embryonic stem cells can be used to generate gastruloids-three-dimensional multicellular aggregates that differentiate to form derivatives of the three germ layers organized spatiotemporally, without additional extra-embryonic tissues. Human gastruloids undergo elongation along an anteroposterior axis, and we use spatial transcriptomics to show that they exhibit patterned gene expression. This includes a signature of somitogenesis that suggests that 72-h human gastruloids show some features of Carnegie-stage-9 embryos3. Our study represents an experimentally tractable model system to reveal and examine human-specific regulatory processes that occur during axial organization in early development

Study protocol: a randomised controlled trial investigating the effect of a healthy lifestyle intervention for people with severe mental disorders

<p>Abstract</p> <p>Background</p> <p>The largest single cause of death among people with severe mental disorders is cardiovascular disease (CVD). The majority of people with schizophrenia and bipolar disorder smoke and many are also overweight, considerably increasing their risk of CVD. Treatment for smoking and other health risk behaviours is often not prioritized among people with severe mental disorders. This protocol describes a study in which we will assess the effectiveness of a healthy lifestyle intervention on smoking and CVD risk and associated health behaviours among people with severe mental disorders.</p> <p>Methods/Design</p> <p>250 smokers with a severe mental disorder will be recruited. After completion of a baseline assessment and an initial face-to-face intervention session, participants will be randomly assigned to either a multi-component intervention for smoking cessation and CVD risk reduction or a telephone-based minimal intervention focusing on smoking cessation. Randomisation will be stratified by site (Newcastle, Sydney, Melbourne, Australia), Body Mass Index (BMI) category (normal, overweight, obese) and type of antipsychotic medication (typical, atypical). Participants will receive 8 weekly, 3 fortnightly and 6 monthly sessions delivered face to face (typically 1 hour) or by telephone (typically 10 minutes). Assessments will be conducted by research staff blind to treatment allocation at baseline, 15 weeks, and 12-, 18-, 24-, 30- and 36-months.</p> <p>Discussion</p> <p>This study will provide comprehensive data on the effect of a healthy lifestyle intervention on smoking and CVD risk among people with severe mental disorders. If shown to be effective, this intervention can be disseminated to treating clinicians using the treatment manuals.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry (ANZCTR) identifier: <a href="http://www.anzctr.org.au/ACTRN12609001039279.aspx">ACTRN12609001039279</a></p