The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats

BACKGROUND: Placental ischemia and hypertension, characteristic features of preeclampsia, are associated with impaired cerebral blood flow (CBF) autoregulation and cerebral edema. However, the factors that contribute to these cerebral abnormalities are not clear. Several lines of evidence suggest that angiotensin II can impact cerebrovascular function; however, the role of the renin angiotensin system in cerebrovascular function during placental ischemia has not been examined. We tested whether the angiotensin type 1 (AT1) receptor contributes to impaired CBF autoregulation in pregnant rats with placental ischemia caused by surgically reducing uterine perfusion pressure. METHODS: Placental ischemic or sham operated rats were treated with vehicle or losartan from gestational day (GD) 14 to 19 in the drinking water. On GD 19, we assessed CBF autoregulation in anesthetized rats using laser Doppler flowmetry. RESULTS: Placental ischemic rats had impaired CBF autoregulation that was attenuated by treatment with losartan. In addition, we examined whether an agonistic autoantibody to the AT1 receptor (AT1-AA), reported to be present in preeclamptic women, contributes to impaired CBF autoregulation. Purified rat AT1-AA or vehicle was infused into pregnant rats from GD 12 to 19 via mini-osmotic pumps after which CBF autoregulation was assessed. AT1-AA infusion impaired CBF autoregulation but did not affect brain water content. CONCLUSIONS: These results suggest that the impaired CBF autoregulation associated with placental ischemia is due, at least in part, to activation of the AT1 receptor and that the RAS may interact with other placental factors to promote cerebrovascular changes common to preeclampsia

To wet or not to wet: that is the question

Wetting transitions have been predicted and observed to occur for various combinations of fluids and surfaces. This paper describes the origin of such transitions, for liquid films on solid surfaces, in terms of the gas-surface interaction potentials V(r), which depend on the specific adsorption system. The transitions of light inert gases and H2 molecules on alkali metal surfaces have been explored extensively and are relatively well understood in terms of the least attractive adsorption interactions in nature. Much less thoroughly investigated are wetting transitions of Hg, water, heavy inert gases and other molecular films. The basic idea is that nonwetting occurs, for energetic reasons, if the adsorption potential's well-depth D is smaller than, or comparable to, the well-depth of the adsorbate-adsorbate mutual interaction. At the wetting temperature, Tw, the transition to wetting occurs, for entropic reasons, when the liquid's surface tension is sufficiently small that the free energy cost in forming a thick film is sufficiently compensated by the fluid- surface interaction energy. Guidelines useful for exploring wetting transitions of other systems are analyzed, in terms of generic criteria involving the "simple model", which yields results in terms of gas-surface interaction parameters and thermodynamic properties of the bulk adsorbate.Comment: Article accepted for publication in J. Low Temp. Phy

VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma

Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor κB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC

Efeito do tratamento com aminoetoxivinilglicina (AVG) na queda pré-colheita e na maturação dos frutos em macieiras

ABSTRACTApple trees cultivars Gala and Fuji were sprayed four weeks before commercial harvest with aminoethoxyvinilglycine (AVG), at doses of 0, 125, or 250 mg L-1, and assessed for preharvest fruit drop, fruit growth, and maturation on tree. In 'Gala', 64 days after AVG spraying, fruit drop for control treatment was 85%, and AVG (at 125 and 250 mg L-1) reduced it to 10%. In 'Fuji', 64 days after AVG spraying, fruit drop for control was 6%, while treatments with AVG (at 125 and 250 mg L-1) increased fruit drop to 10%. AVG was a powerful retardant of fruit maturation for 'Gala' but not for 'Fuji'. In 'Gala', the most affected attribute was the skin background color, followed, in decreasing order, by soluble solids content, the starch index, skin red color, the flesh firmness, and titratable acidity. In 'Gala', only flesh firmness retention was improved by increasing AVG dose from 125 mg L-1 to 250 mg L-1. The AVG at 250 mg L-1 inhibited "Gala" late fruit growth but not 'Fuji'. __________________________________________________________________________________ RESUMOMacieiras, das cultivares Gala e Fuji, foram pulverizadas quatro semanas antes do início da colheita comercial dos frutos com aminoetoxivinilglicina (AVG), nas concentrações de 0; 125 ou 250 mg L-1, e avaliadas quanto à queda de frutos na pré-colheita, o crescimento e maturação dos frutos. Na cultivar Gala, 64 dias após a pulverização com AVG, a queda pré-colheita no tratamento-controle era de 85%, mas os tratamentos com AVG (125 e 250 mg L-1) reduziram esta queda para 10%. Na cultivar Fuji, 64 dias após a pulverização com AVG, a queda de frutos no tratamento-controle era de 6%, e os tratamentos com AVG (125 e 250 mg L-1) aumentaram esta queda para 10%. Tratamentos com AVG retardaram substancialmente a maturação dos frutos da cultivar Gala, mas não da 'Fuji'. Na cultivar Gala, o atributo mais afetado foi a cor de fundo da casca, seguido, em ordem decrescente, pelo conteúdo de sólidos solúveis totais, índice de iodo-amido, cor vermelha da casca, firmeza de polpa e acidez titulável. Na cultivar Gala, apenas a retenção de firmeza de polpa foi significativamente aumentada com o aumento na concentração de AVG de 125 mg L-1 para 250 mg L-1. A concentração de 250 mg L-1 inibiu o crescimento final de frutos na cultivar Gala, mas não na 'Fuji'

Probing exotic phenomena at the interface of nuclear and particle physics with the electric dipole moments of diamagnetic atoms: A unique window to hadronic and semi-leptonic CP violation

The current status of electric dipole moments of diamagnetic atoms which involves the synergy between atomic experiments and three different theoretical areas -- particle, nuclear and atomic is reviewed. Various models of particle physics that predict CP violation, which is necessary for the existence of such electric dipole moments, are presented. These include the standard model of particle physics and various extensions of it. Effective hadron level combined charge conjugation (C) and parity (P) symmetry violating interactions are derived taking into consideration different ways in which a nucleon interacts with other nucleons as well as with electrons. Nuclear structure calculations of the CP-odd nuclear Schiff moment are discussed using the shell model and other theoretical approaches. Results of the calculations of atomic electric dipole moments due to the interaction of the nuclear Schiff moment with the electrons and the P and time-reversal (T) symmetry violating tensor-pseudotensor electron-nucleus are elucidated using different relativistic many-body theories. The principles of the measurement of the electric dipole moments of diamagnetic atoms are outlined. Upper limits for the nuclear Schiff moment and tensor-pseudotensor coupling constant are obtained combining the results of atomic experiments and relativistic many-body theories. The coefficients for the different sources of CP violation have been estimated at the elementary particle level for all the diamagnetic atoms of current experimental interest and their implications for physics beyond the standard model is discussed. Possible improvements of the current results of the measurements as well as quantum chromodynamics, nuclear and atomic calculations are suggested.Comment: 46 pages, 19 tables and 16 figures. A review article accepted for EPJ

Genome-wide Screening Identifies SFMBT1 as an Oncogenic Driver in Cancer with VHL Loss

von Hippel-Lindau (VHL) is a critical tumor suppressor in clear cell renal cell carcinomas (ccRCCs). It is important to identify additional therapeutic targets in ccRCC downstream of VHL loss besides hypoxia-inducible factor 2α (HIF2α). By performing a genome-wide screen, we identified Scm-like with four malignant brain tumor domains 1 (SFMBT1) as a candidate pVHL target. SFMBT1 was considered to be a transcriptional repressor but its role in cancer remains unclear. ccRCC patients with VHL loss-of-function mutations displayed elevated SFMBT1 protein levels. SFMBT1 hydroxylation on Proline residue 651 by EglN1 mediated its ubiquitination and degradation governed by pVHL. Depletion of SFMBT1 abolished ccRCC cell proliferation in vitro and inhibited orthotopic tumor growth in vivo. Integrated analyses of ChIP-seq, RNA-seq, and patient prognosis identified sphingosine kinase 1 (SPHK1) as a key SFMBT1 target gene contributing to its oncogenic phenotype. Therefore, the pVHL-SFMBT1-SPHK1 axis serves as a potential therapeutic avenue for ccRCC. © 2020 Elsevier Inc.The pVHL-SFMBT1-SPHK1 axis serves as a potential therapeutic avenue for ccRCC

Research trends in combinatorial optimization

Acknowledgments This work has been partially funded by the Spanish Ministry of Science, Innovation, and Universities through the project COGDRIVE (DPI2017-86915-C3-3-R). In this context, we would also like to thank the Karlsruhe Institute of Technology. Open access funding enabled and organized by Projekt DEAL.Peer reviewedPublisher PD

The Theory of Brown Dwarfs and Extrasolar Giant Planets

Straddling the traditional realms of the planets and the stars, objects below the edge of the main sequence have such unique properties, and are being discovered in such quantities, that one can rightly claim that a new field at the interface of planetary science and and astronomy is being born. In this review, we explore the essential elements of the theory of brown dwarfs and giant planets, as well as of the new spectroscopic classes L and T. To this end, we describe their evolution, spectra, atmospheric compositions, chemistry, physics, and nuclear phases and explain the basic systematics of substellar-mass objects across three orders of magnitude in both mass and age and a factor of 30 in effective temperature. Moreover, we discuss the distinctive features of those extrasolar giant planets that are irradiated by a central primary, in particular their reflection spectra, albedos, and transits. Aspects of the latest theory of Jupiter and Saturn are also presented. Throughout, we highlight the effects of condensates, clouds, molecular abundances, and molecular/atomic opacities in brown dwarf and giant planet atmospheres and summarize the resulting spectral diagnostics. Where possible, the theory is put in its current observational context.Comment: 67 pages (including 36 figures), RMP RevTeX LaTeX, accepted for publication in the Reviews of Modern Physics. 30 figures are color. Most of the figures are in GIF format to reduce the overall size. The full version with figures can also be found at: http://jupiter.as.arizona.edu/~burrows/papers/rm