The Brain-Heart Connection: Frontal Cortex and Left Ventricle Angiotensinase Activities in Control and Captopril-Treated Hypertensive Rats—A Bilateral Study

The model of neurovisceral integration suggests that the frontal cortex (FC) and the cardiovascular function are reciprocally and asymmetrically connected. We analyzed several angiotensinase activities in the heart left ventricle (VT) of control and captopril-treated SHR, and we search for a relationship between these activities and those determined in the left and right FC. Captopril was administered in drinking water for 4 weeks. Samples from the left VT and from the left and right FC were obtained. Soluble and membrane-bound enzymatic activities were measured fluorometrically using arylamides as substrates. The weight of heart significantly decreased after treatment with captopril, mainly, due to the reduction of the left VT weight. In the VT, no differences for soluble activities were observed between control and treated SHR. In contrast, a generalized significant reduction was observed for membrane-bound activities. The most significant correlations between FC and VT were observed in the right FC of the captopril-treated group. The other correlations, right FC versus VT and left FC versus VT in controls and left FC versus VT in the captopril group, were few and low. These results confirm that the connection between FC and cardiovascular system is asymmetrically organized

Interactions of Kid–Kis toxin–antitoxin complexes with the parD operator-promoter region of plasmid R1 are piloted by the Kis antitoxin and tuned by the stoichiometry of Kid–Kis oligomers

The parD operon of Escherichia coli plasmid R1 encodes a toxin–antitoxin system, which is involved in plasmid stabilization. The toxin Kid inhibits cell growth by RNA degradation and its action is neutralized by the formation of a tight complex with the antitoxin Kis. A fascinating but poorly understood aspect of the kid–kis system is its autoregulation at the transcriptional level. Using macromolecular (tandem) mass spectrometry and DNA binding assays, we here demonstrate that Kis pilots the interaction of the Kid–Kis complex in the parD regulatory region and that two discrete Kis-binding regions are present on parD. The data clearly show that only when the Kis concentration equals or exceeds the Kid concentration a strong cooperative effect exists between strong DNA binding and Kid(2)–Kis(2)–Kid(2)–Kis(2) complex formation. We propose a model in which transcriptional repression of the parD operon is tuned by the relative molar ratio of the antitoxin and toxin proteins in solution. When the concentration of the toxin exceeds that of the antitoxin tight Kid(2)–Kis(2)–Kid(2) complexes are formed, which only neutralize the lethal activity of Kid. Upon increasing the Kis concentration, (Kid(2)–Kis(2))(n) complexes repress the kid–kis operon

SARS-CoV-2-Mediated Lung Edema and Replication Are Diminished by Cystic Fibrosis Transmembrane Conductance Regulator Modulators

20 Pág.Coronaviruses (CoVs) of genera α, β, γ, and δ encode proteins that have a PDZ-binding motif (PBM) consisting of the last four residues of the envelope (E) protein (PBM core). PBMs may bind over 400 cellular proteins containing PDZ domains (an acronym formed by the combination of the first letter of the names of the three first proteins where this domain was identified), making them relevant for the control of cell function. Three highly pathogenic human CoVs have been identified to date: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. The PBMs of the three CoVs were virulence factors. SARS-CoV mutants in which the E protein PBM core was replaced by the E protein PBM core from virulent or attenuated CoVs were constructed. These mutants showed a gradient of virulence, depending on whether the alternative PBM core introduced was derived from a virulent or an attenuated CoV. Gene expression patterns in the lungs of mice infected with SARS-CoVs encoding each of the different PBMs were analyzed by RNA sequencing of infected lung tissues. E protein PBM of SARS-CoV and SARS-CoV-2 dysregulated gene expression related to ion transport and cell homeostasis. Decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA, essential for alveolar edema resolution, was shown. Reduced CFTR mRNA levels were associated with edema accumulation in the alveoli of mice infected with SARS-CoV and SARS-CoV-2. Compounds that increased CFTR expression and activity, significantly reduced SARS-CoV-2 growth in cultured cells and protected against mouse infection, suggesting that E protein virulence is mediated by a decreased CFTR expression. IMPORTANCE Three highly pathogenic human CoVs have been identified: SARS-CoV, MERS-CoV, and SARS-CoV-2. The E protein PBMs of these three CoVs were virulence factors. Gene expression patterns associated with the different PBM motifs in the lungs of infected mice were analyzed by deep sequencing. E protein PBM motif of SARS-CoV and SARS-CoV-2 dysregulated the expression of genes related to ion transport and cell homeostasis. A decrease in the mRNA expression of the cystic fibrosis transmembrane conductance regulator (CFTR), which is essential for edema resolution, was observed. The reduction of CFTR mRNA levels was associated with edema accumulation in the lungs of mice infected with SARS-CoV-2. Compounds that increased the expression and activity of CFTR drastically reduced the production of SARS-CoV-2 and protected against its infection in a mice model. These results allowed the identification of cellular targets for the selection of antivirals.This work was supported by grants from the Government of Spain (BIO2016-75549-R; PID2019-107001RB-I00 AEI/FEDER, UE; SEV 2017-0712 and PIE_INTRAMURAL_LINEA 1- 202020E079), CSIC (PIE_INTRAMURAL-202020E043), the European Zoonotic Anticipation and Preparedness Initiative (ZAPI) (IMI_JU_115760), the European Commission (H2020-SC1- 2019, ISOLDA Project No. 848166-2), and the U.S. National Institutes of Health (NIH) (2P01AI060699). J.M.H. received a contract from Comunidad de Madrid (Y2020/BIO-6576, COVID-PREclinical-MODels-CM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. In vivo experiments were performed at INIA-CISA (Madrid, Spain)Peer reviewe

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Interaction between Angiotensinase Activities in Pituitary and Adrenal Glands of Wistar–Kyoto and Spontaneously Hypertensive Rats under Hypotensive or Hypertensive Treatments

This research was supported by the Ministry of Science and Innovation through project no. SAF 2008 04685 C02 01.In the present study, we analyzed the activity of several aminopeptidases (angiotensinases) involved in the metabolism of various angiotensin peptides, in pituitary and adrenal glands of untreated Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR) or treated with the antihypertensive drugs captopril and propranolol or with the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). Intra- and inter-gland correlations between angiotensinase activities were also calculated. Membrane-bound alanyl-, cystinyl-, and glutamylaminopeptidase activities were determined fluorometrically using aminoacyl- -naphthylamide as substrates. Depending on the type of angiotensinase analyzed, the results reflect a complex picture showing substantial differences between glands, strains, and treatments. Alanyl-aminopeptidase responsible for the metabolism of Ang III to Ang IV appears to be the most active angiotensinase in both pituitary and adrenals of WKY and particularly in SHR. Independently of treatment, most positive correlations are observed in the pituitary gland of WKY whereas such positive correlations are predominant in adrenals of SHR. Negative inter-gland correlations were observed in control SHR and L-NAME treated WKY. Positive inter-gland correlations were observed in captopril-treated SHR and propranolol-treated WKY. These results may reflect additional mechanisms for increasing or decreasing systolic blood pressure in WKY or SHR.Spanish Government SAF 2008 04685 C02 0

A 500 kyr record of global sea level oscillations in the Gulf of Lion, Mediterranean Sea: new insights into MIS 3 sea level variability

Borehole PRGL1-4 drilled in the upper slope of the Gulf of Lion provides an exceptional record to investigate the impact of late Pleistocene orbitally-driven glacio-eustatic sea-level oscillations on the sedimentary outbuilding of a river fed continental margin. High-resolution grain-size and geochemical records supported by oxygen isotope chronostratigraphy allow reinterpreting the last 500 ka upper slope seismostratigraphy of the Gulf of Lion. Five main sequences, stacked during the sea-level lowering phases of the last five glacial-interglacial 100-kyr cycles, form the upper stratigraphic outbuilding of the continental margin. The high sensitivity of the grain-size record down the borehole to sea-level oscillations can be explained by the great width of the Gulf of Lion continental shelf. Sea level driven changes in accommodation space over the shelf cyclically modified the depositional mode of the entire margin. PRGL1-4 data also illustrate the imprint of sea-level oscillations at millennial time-scale, as shown for Marine Isotopic Stage 3, and provide unambiguous evidence of relative high sea-levels at the onset of each Dansgaard-Oeschger Greenland warm interstadial. The PRGL1-4 grain-size record represents the first evidence for a one-to-one coupling of millennial time-scale sea-level oscillations associated with each Dansgaard-Oeschger cycle

Macromolecular tandem mass spectrometry reveals topology of Kid–Kis– DNA region I complexes

<p><b>Copyright information:</b></p><p>Taken from "Interactions of Kid–Kis toxin–antitoxin complexes with the operator-promoter region of plasmid R1 are piloted by the Kis antitoxin and tuned by the stoichiometry of Kid–Kis oligomers"</p><p></p><p>Nucleic Acids Research 2007;35(5):1737-1749.</p><p>Published online 21 Feb 2007</p><p>PMCID:PMC1865072.</p><p>© 2007 The Author(s)</p> Tandem mass spectrometry was performed on Kid–Kis and Kid–Kis– DNA in ammonium acetate (50 mM), pH 5.8. () Tandem mass spectra of Kis–Kid–Kid–Kis after selection of the 20 ion and () tandem mass spectra of Kis–Kid–Kid–Kis– DNA complex after selection of the 21 ion. Acceleration voltages varied between 25 and 65 V. Kid and Kis are indicated with blue rectangles and orange ellipses, respectively and the DNA fragment with double strand. Each complex is represented by an appropriate combination of rectangles, ellipses and/or DNA double strand

Brand management at a local scale: a case of ‘ghost awareness’

This research builds upon the study of a multinational brand relationship with the local community to test a model of analysis of brand awareness. In the model, the evaluation of two dimensions of the phenomenon is suggested: the type of awareness and the drivers of awareness. And the case study was developed through the examination of two groups of stakeholders: the general population and the local opinion leaders. The results suggest that the corporate brand has high levels of awareness, but faces a structural identity problem because of the existence of a strong competitor: a corporate brand that has left the region decades ago but whose recall is still very strong among local stakeholders. We call this phenomenon ‘ghost awareness’. Following these clues, we present some recommendations that can be adopted by companies with the same perception problems