122,128 research outputs found
TRP120-Hh-SLiM upregulates GLI-1 in THP-1 cells and primary human monocytes.
(A) TRP120-TR-Hh and TRP120-Hh-SLiM sequences contain the Hh homology sequence identified by BLAST analysis. TRP120-Hh-SLiM-mut contains glycine and alanine substitutions in the Hh SLiM region and is used as a negative control. TRP120-TR (-) is a sequence within the TRP120-TR that does not contain the defined Hh homology sequence. (B) Confocal immunofluorescence microscopy of untreated (-) or peptide treated THP-1 cells. THP-1 cells were stained with GLI-1 antibody. The micrograph shows increased levels of GLI-1 (green) in TRP120-TR-Hh and TRP120-Hh-SLiM treated, but not untreated, TRP120-TR (-) or TRP120-Hh-SLiM-mut treated THP-1 cells 6 h post-treatment (hpt) (scale bar = 10 μm). (C) Confocal immunofluorescence microscopy of untreated or SLiM/SLiM mutant peptide treated primary human monocytes harvested at 10 h. The TRP120-Hh-SLiM sequence upregulates GLI-1 (green) in primary human monocytes, but the corresponding mutant sequence does not (scale bar = 10 μm). (B-C) Experiments were performed with at least three biological and technical replicates. Randomized areas/slide (n = 10) were used to detect GLI-1 nuclear translocation. (D-E) Intensity graphs demonstrate the mean nuclear accumulation of GLI-1 in respective THP-1 cells and primary human monocytes. Analysis was performed using ImageJ and determining mean grey value from randomized areas/slide (n = 10). (F-G) Hh signaling PCR arrays were utilized to analyze the expression of 84 Hh genes. In brief, THP-1 cells were treated with TRP120-Hh-SLiM or TRP120-Hh-SLiM-mut (50 and 500 ng/mL) or left untreated (negative control). THP-1 cells were harvested at 24 h with three biological and technical replicates. The tables represent the fold change in gene expression at each concentration. (F) The upregulation of gene expression in TRP120-Hh-SLiM-treated cells compared to untreated cells at respective concentrations. (G) Upregulation of gene expression in TRP120-Hh-SLiM treated cells compared to TRP120-Hh-SLiM-mut treated cells at respective concentrations.</p
Sectoral allocation by gender of Latin American workers over the liberalization period of the 1990s
The recent restructuring of Latin American economies has renewed interest in the effects of trade liberalization, on labor markets, and on the gender division of labor. The author does not attempt to establish casuality between economic reforms, and the types of jobs that men and women hold. Instead, she provides a detailed description of the trends in male, and female formal, and informal sector participation during the economic reform period in Argentina, Brazil, and Costa Rica. The author first compares the gender composition of the formal, informal wage, and self-employment sectors in a year before reforms (1988 for Argentina, 1989 for Brazil, and Costa Rica), and a year after reforms implementation (1997 for Argentina, 1995 for Brazil and Costa Rica). Although women continued to be more likely than men to work in the informal wage sector, there is no trend of"masculinization"or"feminization"of the informal sector, or any other. Instead, in Argentina men have overtaken women as the most prevalent workers in the informal wage sector, while in Brazil, the opposite has occurred (as men move into self-employment). In Costa Rica there have been no statistical, observable changes. The author then considers the distribution across sectors within each gender group, to identify whether men, and women are more likely to select different sectors in the post-reform period relative to the pre-reform period. Among both men, and women in all three countries (except Brazilian men), workers have become more likely to hold informal wage jobs, and less likely to hold formal sector jobs. Trends in human capital accumulation explain these changes for both men, and women, while changes in gender roles, primarily in homecare and marriage, do not seem to have an effect.Health Monitoring&Evaluation,Labor Policies,Population&Development,Public Health Promotion,Environmental Economics&Policies,Health Monitoring&Evaluation,Environmental Economics&Policies,Population&Development,Banks&Banking Reform,Work&Working Conditions
The impact of alcohol on vestibular function in relation to legal limit of 0.25 mg/L breath alcohol concentration
Signaling properties of Hh-N.
<p>(A) Hemolymph Hh levels of larvae secreting Hh, Hh-N<sup>Med</sup>, Hh-N<sup>Low</sup>, or Hh+Hh-N<sup>Low</sup> from the fat body, analyzed by WB. (B) Phosphorylation status of Fused in wing discs from larvae secreting different combinations of Hh and Hh-N from the fat body, analyzed by WB. (C) Levels of Ci repressor (Ci<sub>75</sub>) and Ci<sub>155</sub> (full-length) in wing discs of larvae secreting different combinations of Hh and Hh-N from the fat body, analyzed by WB. (D) Wing disc anterior to posterior compartment ratio of larvae secreting different combinations of Hh and Hh-N from the fat body. Error bars indicate ± SEM (<i>n</i> = 20). *<i>p</i><0.05; **<i>p</i><0.005; ***<i>p</i><0.0005; ****<i>p</i><0.00005. (E–G) Quantification of (E) Hh, (F) Ci<sub>155</sub>, and (G) Collier staining of wing discs shown in (H). Translucent lines indicate ± SD (<i>n</i> = 12). (H) IF of wing discs from larvae secreting different combinations of Hh and Hh-N from the fat body, stained for Hh, Ci<sub>155</sub>, and Collier. A denotes the anterior compartment, P the posterior compartment; yellow lines indicate the compartment boundary. Scale bar = 50 µm.</p
Anti-TRP120-Hh-SLiM antibody blocks Hh signaling and GLI-1 nuclear translocation.
(A) E. chaffeensis (MOI 100) and SLiMs were incubated with α-TRP120-I1 (targets TRP120 sequence SKVEQEETNPEVLIKDLQDVAS) or α-TRP32 (neg ctrl) (1.5 μg/mL) for 1 h or overnight, respectively, before incubation with THP-1 cells. THP-1 cells were harvested at 10 hpt, immunostained with GLI-1 (green), and visualized by confocal fluorescence microscopy. Scale bar = 10 μm. 10 randomized areas/slide were used to detect GLI-1 nuclear translocation. (B) Intensity graph demonstrates the mean nuclear accumulation of GLI-1 in respective THP-1 cells. Analysis was performed using ImageJ and determining mean grey value from randomized areas/slide (n = 10). (C) Western blot analysis of treatment groups with GAPDH as a loading control. Data are represented as means ± SD (*pE. chaffeensis or TRP120-Hh-SLiM compared to α-TRP32. Untreated cells were incubated with α-TRP120-I1 or α-TRP32 as negative controls. Experiments were performed with at least three biological and technical replicates and significance was determined through t-test analysis. Randomized areas/slide (n = 10) were used to detect GLI-1 nuclear translocation.</p
<i>Axin2</i> transcripts in chicken embryos from stage HH 23 to HH 32.
(A) HH 23: expression pattern resembles what is described in Fig 2. Limbs, inner ear, brain, eye, and tb express Axin2 (A). (B, B.1 & B.2) HH 24: Axin2 expression in the ov (B.1, white arrow) and ba (B.1), as well as in nt and isf(B.2, dorsal view). (C, C.1) HH 25: Axin2 is expressed at similar embryonic structures with little change. (D, D.1, D.2, D.3) HH 26: Axin2 expression in ba (D, black and red arrow; D.2), ov(D.2), lb(D.1), brain (D), eye (D), isf (D.3, white arrow) and nt (D.3). (E) HH27: Axin2 transcripts in the facial whilst (E, white arrow), in the ba (black arrows), as well as in lb. The dorsal view (E.1) expression in the nt (white arrow). Ba display specific staining for cAxin2 (HH 28: F & HH 29: G, white arrows). HH 28 and 29: intense expression in the embryonic shoulder (F & G, red arrows). Expression of Axin2 in the forming interdigital spaces (F & G, black arrows). (H, H.1) HH 31: expression of Axin2 mRNA in lb and apoptotic interdigital zones (H, black arrow), at the ee(H, red arrow) and in the fb(H & H.1, white arrows). (I, I.1) HH 32: Axin2 transcripts in the eye (I, white arrow), ee (I, red arrow) and in the fb (I.1, white arrow). lb-limb buds, ov-otic vesicle, ba-branchial arches, tb-tail bud, nt-neural tube, isf-intersomitic furrow, fb-feather buds, ee-external ear.</p
Signaling properties of Lpp-associated Hh and Hh-N*.
<p>(A) Cartoon depicting the fat body to wing disc signaling assay of secreted Hh. (B) IF of wing discs from larvae secreting Hh from the fat body, and Lpp RNAi larvae, stained for Hh, Ci<sub>155</sub>, and Lpp. Scale bar = 50 µm. In all wing discs, A denotes the anterior compartment, P the posterior compartment; yellow lines indicate the compartment boundary. Scale bar = 50 µm. (C and D) Quantification of (C) Hh and (D) Ci<sub>155</sub> staining of wing discs shown in (B). Translucent lines indicate ±SD (<i>n</i> = 12). (E) Phosphorylation status of Fused in wing discs of larvae secreting Hh from the fat body and Lpp RNAi larvae, analyzed by WB. (F) Ci<sub>75</sub> repressor levels in wing discs of larvae secreting Hh from the fat body, and Lpp RNAi larvae, analyzed by WB. (G) IF of wing discs from larvae secreting Hh or Hh-N* from the fat body, stained for <i>dpp</i>LacZ and, to mark cell boundaries, with phalloidin. Hh-N* was generated by expressing Hh in the fat body of Lpp RNAi animals. Scale bar = 50 µm. (H) Wing disc anterior to posterior compartment ratio of larvae secreting Hh or Hh-N* from the fat body and Lpp RNAi larvae. Error bars indicate ± SEM (<i>n</i> = 20). ***<i>p</i><0.0005; ****<i>p</i><0.00005.</p
Physalin H from Solanum nigrum as an Hh signaling inhibitor blocks GLI1–DNA-complex formation
Hedgehog (Hh) signaling plays an important role in embryonic development, cell maintenance and cell proliferation. Moreover, Hh signaling contributes to the growth of cancer cells. Physalins are highly oxidized natural products with a complex structure. Physalins (1–7) were isolated from Solanum nigrum (Solanaceae) collected in Bangladesh by using our cell-based assay. The isolated physalins included the previously reported Hh inhibitors 5 and 6. Compounds 1 and 4 showed strong inhibition of GLI1 transcriptional activity, and exhibited cytotoxicity against cancer cell lines with an aberrant activation of Hh signaling. Compound 1 inhibited the production of the Hh-related proteins patched (PTCH) and BCL2. Analysis of the structures of different physalins showed that the left part of the physalins was important for Hh inhibitory activity. Interestingly, physalin H (1) disrupted GLI1 binding to its DNA binding domain, while the weak inhibitor physalin G (2) did not show inhibition of GLI1-DNA complex formation
Role of in Higgs boson decays to in the 2HDM
33 pages, 5 figures, version published in Phys. Rev. DWithin the Two Higgs Doublet Model (2HDM) with conservation
and a softly broken symmetry, we analyze the flavor changing Higgs decays
( refers jointly to the two decay channels and ), where is identified with the SM-like Higgs boson discovered at the
LHC. We provide a comprehensive study of the decay width
with particular focus on the most relevant effects from the triple Higgs
coupling . Furthermore, we consider all the relevant
theoretical and experimental constraints to determine which predictions for the
are still allowed by the current data. We
find that the predictions for in types II and
III can be several orders of magnitude smaller compared to the SM value. In
contrast, in type I and IV we find that the predicted enhancements in the decay
rates with respect to the SM of up to about 70% and 50%, respectively, are
still allowed. We discuss how these deviations from the SM are caused by
interference effects controlled by the coupling which can
be large for very heavy . To better understand the role of
in the decay we derive and analyze here the
analytical results for the one-loop effective vertex that is generated by
integrating out the heavy .The present work has received financial support from the
grant IFT Centro de Excelencia Severo Ochoa CEX2020-
001007-S funded by MCIN/AEI/10.13039/501100011033.
The work of F. A. and S. H. was also supported in part
by the grant No. PID2019–110058 GB-C21 funded by
MCIN/AEI/10.13039/501100011033 and by “ERDF A
way of making Europe.” F. A. and M. J. H. also acknowledge financial support from the Spanish “Agencia Estatal
de Investigación” (AEI) and the EU “Fondo Europeo de
Desarrollo Regional” (FEDER) through the project
No. PID2019-108892RB-I00 funded by MCIN/AEI/
10.13039/501100011033 and from the European Union’s
Horizon 2020 research and innovation programme
under the Marie Sklodowska-Curie Grant Agreement
No. 860881-HIDDeN. The work of F. A. was also supported by the Spanish Ministry of Science and Innovation
via an Formación de Profesorado Universitario (FPU) grant
with code No. FPU18/06634.Peer reviewe
Taming a leading theoretical uncertainty in HH measurements via accurate simulations for production
Abstract We present a new simulation for Higgs boson production in association with bottom quarks ( b b ¯ H ) at next-to-leading order (NLO) accuracy matched to parton showers in hadronic collisions. Both contributions, the standard one proportional to the bottom-quark Yukawa coupling and the loop-induced one proportional to the top-quark Yukawa coupling from the gluon-fusion process, are taken into account in a scheme with massive bottom quarks. Therefore, we provide the full simulation of the b b ¯ H final state in the Standard Model, which constitutes also a crucial background to measurements for Higgs-boson pair (HH) production at the Large Hadron Collider when at least one of the Higgs bosons decays to bottom quarks. So far, the modeling of the b b ¯ H final state induced one of the dominant theoretical uncertainties to HH measurements, as the gluon-fusion component was described only at the leading order (LO) with uncertainties of O (100%). Including NLO corrections in its simulation allows us to reduce the scale dependence to O (50%) so that it becomes subdominant with respect to other systematic uncertainties. As a case study, we provide an in-depth analysis of the b b ¯ H background to HH measurements with realistic selection cuts in the 2b2γ channel. We also compare our novel simulation with the currently-employed ones, discussing possible issues and shortcomings of a scheme with massless bottom quarks. Finally, we propagate the effect of the new b b ¯ H simulation to HH searches in the 2b2γ and 2b2τ final states, and we find an improvement of up to 10% (20%) on the current (HL-LHC) limits on σ SM HH
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