2,512 research outputs found
Personalized medicine—a modern approach for the diagnosis and management of hypertension
The main goal of treating hypertension is to reduce blood pressure to physiological levels and thereby prevent risk of cardiovascular disease and hypertension-associated target organ damage. Despite reductions in major risk factors and the availability of a plethora of effective antihypertensive drugs, the control of blood pressure to target values is still poor due to multiple factors including apparent drug resistance and lack of adherence. An explanation for this problem is related to the current reductionist and ‘trial-and-error’ approach in the management of hypertension, as we may oversimplify the complex nature of the disease and not pay enough attention to the heterogeneity of the pathophysiology and clinical presentation of the disorder. Taking into account specific risk factors, genetic phenotype, pharmacokinetic characteristics, and other particular features unique to each patient, would allow a personalized approach to managing the disease. Personalized medicine therefore represents the tailoring of medical approach and treatment to the individual characteristics of each patient and is expected to become the paradigm of future healthcare. The advancement of systems biology research and the rapid development of high-throughput technologies, as well as the characterization of different –omics, have contributed to a shift in modern biological and medical research from traditional hypothesis-driven designs toward data-driven studies and have facilitated the evolution of personalized or precision medicine for chronic diseases such as hypertension
Pseudomonas aeruginosa LptE is crucial for LptD assembly, cell envelope integrity, antibiotic resistance and virulence
Lipopolysaccharide (LPS) is an essential structural component of the outer membrane (OM) of most Gram-negative bacteria. In the model organism Escherichia coli, LPS transport to the OM requires seven essential proteins (LptABCDEFG) that form a continuous bridge across the cell envelope. In Pseudomonas aeruginosa the recently-demonstrated essentiality of LptD and LptH, the P. aeruginosa LptA homologue, confirmed the crucial role of the Lpt system and, thus, of LPS in OM biogenesis in this species. Surprisingly, independent high-throughput transposon mutagenesis studies identified viable P. aeruginosa insertion mutants in the lptE gene, suggesting that it might be dispensable for bacterial growth. To test this hypothesis, we generated an lptE conditional mutant in P. aeruginosa PAO1. LptE depletion only slightly impairs P. aeruginosa growth in vitro. Conversely, LptE is important for cell envelope stability, antibiotic resistance and virulence in an insect model. Interestingly, the maturation and OM localization of LPS is only marginally affected in LptE-depleted cells, while the levels of the OM component LptD are strongly reduced. This suggests that P. aeruginosa LptE might not be directly involved in LPS transport, although it is clearly essential for the maturation and/or stability of LptD. While poor functionality of LptD caused by LptE depletion is somehow tolerated by P. aeruginosa, this has a high cost in terms of cell integrity, drug resistance and virulence, highlighting LptE function(s) as an interesting target to weaken P. aeruginosa defenses and reduce its infectivity
Quaterpyridine Ligands for Panchromatic Ru(II) Dye Sensitizers
A new general synthetic access to carboxylated quaterpyridines (qpy), of interest as ligands for panchromatic dyesensitized solar cell organometallic sensitizers, is presented. The strategic step is a Suzuki−Miyaura cross-coupling reaction,
which has allowed the preparation of a number of representative unsubstituted and alkyl and (hetero)aromatic substituted qpys.
To bypass the poor inherent stability of 2-pyridylboronic acid derivatives, we successfully applied N-methyliminodiacetic acid
(MIDA) boronates as key reagents, obtaining the qpy ligands in good yields up to (quasi)gram quantities. The structural,
spectroscopic (NMR and UV−vis), electrochemical, and electronic characteristics of the qpy have been experimentally and
computationally (DFT) investigated. The easy access to the bis-thiocyanato Ru(II) complex of the parent species of the qpy
series, through an efficient route which bypasses the use of Sephadex column chromatography, is shown. The bis-thiocyanato
Ru(II) complex has been spectroscopically (NMR and UV−vis), electrochemically, and computationally investigated, relating its
properties to those of previously reported Ru(II)−qpy complexes.“This document is the Accepted Manuscript version of a Published Work that appeared in final form in [The Journal of Organic Chemistry], copyright © American Chemical Society after peer review and technical editing by the publisher
c-Src inhibition improves cardiovascular function but not remodeling or fibrosis in Ang II-induced hypertension
c-Src plays an important role in angiotensin II (Ang II) signaling. Whether this member of the Src family kinases is involved in the development of Ang II–induced hypertension and associated cardiovascular damage in vivo remains unknown. Here, we studied Ang II–infused (400 ng/kg/min) mice in which c-Src was partially deleted (c-Src+/−) and in wild-type (WT, c-Src+/+) mice treated with a c-Src inhibitor (CGP077675; 25 mg/kg/d). Ang II increased blood pressure and induced endothelial dysfunction in WT mice, responses that were ameliorated in c-Src+/− and CGP077675-treated mice. Vascular wall thickness and cross-sectional area were similarly increased by Ang II in WT and c-Src+/− mice. CGP077675 further increased cross-sectional area in hypertensive mice. Cardiac dysfunction (ejection fraction and fractional shortening) in Ang II–infused WT mice was normalized in c-Src+/− mice. Increased oxidative stress (plasma thiobarbituric acid–reactive substances, hydrogen peroxide, and vascular superoxide generation) in Ang II–infused WT mice was attenuated in c-Src–deficient and CGP077675-treated mice. Hyperactivation of vascular c-Src, ERK1/2 (extracellular signal–regulated kinase 1/2), and JNK (c-Jun N-terminal kinase) in hypertensive mice was normalized in CGP077675-treated and c-Src+/− mice. Vascular fibronectin was increased by Ang II in all groups and further augmented by CGP077675. Cardiac fibrosis and inflammation induced by Ang II were amplified in c-Src+/− and CGP-treated mice. Our data indicate that although c-Src downregulation attenuates development of hypertension, improves endothelial and cardiac function, reduces oxidative stress, and normalizes vascular signaling, it has little beneficial effect on fibrosis. These findings suggest a divergent role for c-Src in Ang II–dependent hypertension, where c-Src may be more important in regulating redox-sensitive cardiac and vascular function than fibrosis and remodeling
Altermagnetic surface states: towards the observation and utilization of altermagnetism in thin films, interfaces and topological materials
The altermagnetism influences the electronic states allowing the presence of
non-relativistic spinsplittings. Since altermagnetic spin-splitting is present
along specific k-paths of the 3D Brillouin zone, we expect that the
altermagnetic surface states will be present on specific surface orientations.
We unveil the properties of the altermagnetic surface states considering three
representative space groups: tetragonal, orthorhombic and hexagonal. We
calculate the 2D projected Brillouin zone from the 3D Brillouin zone. We study
the surfaces with their respective 2D Brillouin zones establishing where the
spin-splittings with opposite sign merge annihilating the altermagnetic
properties and on which surfaces the altermagnetism is preserved. Looking at
the three principal surface orientations, we find that for several cases two
surfaces are blind to the altermagnetism, while the altermagnetism survives for
one surface orientation. Which surface preserves the altermagnetism depends
also on the magnetic order. We show that an electric field orthogonal to the
blind surface can activate the altermagnetism. Our results predict which
surfaces to cleave in order to preserve altermagnetism in surfaces or
interfaces and this paves the way to observe non-relativistic altermagnetic
spin-splitting in thin films via spin-resolved ARPES and to interface the
altermagnetism with other collective modes. We open future perspectives for the
study of altermagnetic effects on the trivial and topological surface states.Comment: 8 pages, 10 figure
EVIDENCE OF WEAK CHAOS WITHIN PLUG-SLUG TRANSITION IN HORIZONTAL TWO PHASE FLOW
Intermittent behaviour has been observed in gas-liquid flows in a horizontal pipe and a weak sign of deterministic chaos has been diagnosed within a transition from plug to slug flow. The analysis has been performed on the basis of an algorithm which exploits the concept of short-term predictability of chaotic motions. The method is completely non-parametric and works whatever the distribution function of the data points may be. The weak sign of chaos is in contrast with the Lorenz-type systems (strong chaos) and supports the idea of Kolmogorov about irregular motion in hydrodynamical systems
Elevated serum levels of macrophage migration inhibitory factor and stem cell growth factor β in patients with idiopathic and systemic sclerosis associated pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH) can be idiopathic or secondary to autoimmune diseases, and it represents one of the most threatening complications of systemic sclerosis (SSc). Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with proinflammatory functions that appears to be involved in the pathogenesis of hypoxia-induced PH. In SSc patients, high serum levels of MIF have been associated with the development of ulcers and PAH. Stem cell growth factor β (SCGF β) is a human growth factor that, together with MIF, is involved in the pathogenesis of chronic spinal cord injury. The aim of our study was to measure serum levels of MIF in patients with idiopathic and SSc-associated PAH. We enrolled 13 patients with idiopathic PAH and 15 with SSc-associated PAH. We also selected 14 SSc patients without PAH and 12 normal healthy controls, matched for sex and age. PAH was confirmed by right hearth catheterism (mPAP>25 mmHg). MIF and SCGF β levels were measured by ELISA. We found significantly higher circulating levels of MIF and of SCGF β in patients with idiopathic PAH (P=0.03 and P=0.004) and with PAH secondary to SSc (P=0.018 and P=0.023) compared to SSc patients without PAH. Higher levels of MIF were found in those patients with an higher New York Heart Association (NYHA) class (P=0.03). We can hypothesize that MIF and SCGF β are able to play a role in PAH, both idiopathic or secondary, and in the future they may be evaluated as useful biomarkers and prognostic factors for this serious vascular disease
Dirac surface states, multiorbital dimerization and superconductivity in Nb- and Ta-based A15 compounds
Using first-principle calculations, we investigate the electronic,
topological and superconducting properties of NbX (X = Ge, Sn, Sb) and
TaY (Y = As, Sb, Bi) A15 compounds. We demonstrate that these compounds
host Dirac surface states which are related to a nontrivial Z topological
value. The spin-orbit coupling (SOC) splits the eightfold degenerate R point
close to the Fermi level enhancing the amplitude of the spin Hall conductance.
Indeed, despite the moderate spin-orbit of the Nb-compounds, a large spin Hall
effect is also obtained in NbGe and NbSn compounds. We show that the
Coulomb interaction opens the gap at the R point thus making more evident the
occurrence of Dirac surface states. We then investigate the superconducting
properties by determining the strength of the electron-phonon BCS coupling. The
evolution of the critical temperature is tracked down to the 2D limit
indicating a reduction of the transition temperature which mainly arises from
the suppression of the density of states at the Fermi level. Finally, we
propose a minimal tight-binding model based on three coupled
Su-Schrieffer-Heeger chains with t Ta- and Nb-orbitals reproducing the
spin-orbit splittings at the R point among the -bond bands in this class
of compounds. We separate the kinetic parameters in and -bonds,
in intradimer and interdimer hoppings and discuss their relevance for the
topological electronic structure. We point out that NbGe might represent a
Z topological metal with the highest superconducting temperature ever
recorded.Comment: 16 pages, 12 figures in main text, 3 figures in appendix, Paper
submitted to Physical Review
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