34,012 research outputs found
Angiotensin II induces soluble fms-Like tyrosine kinase-1 release via calcineurin signaling pathway in pregnancy
No full textMaternal endothelial dysfunction in preeclampsia is associated with increased soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating antagonist of vascular endothelial growth factor and placental growth factor. Angiotensin II (Ang II) is a potent vasoconstrictor that increases concomitant with sFlt-1 during pregnancy. Therefore, we speculated that Ang II may promote the expression of sFlt-1 in pregnancy. Here we report that infusion of Ang II significantly increases circulating levels of sFlt-1 in pregnant mice, thereby demonstrating that Ang II is a regulator of sFlt-1 secretion in vivo. Furthermore, Ang II stimulated sFlt-1 production in a dose- and time-dependent manner from human villous explants and cultured trophoblasts but not from endothelial cells, suggesting that trophoblasts are the primary source of sFlt-1 during pregnancy. As expected, Ang II-induced sFlt-1 secretion resulted in the inhibition of endothelial cell migration and in vitro tube formation. In vitro and in vivo studies with losartan, small interfering RNA specific for calcineurin and FK506 demonstrated that Ang II-mediated sFlt-1 release was via Ang II type 1 receptor activation and calcineurin signaling, respectively. These findings reveal a previously unrecognized regulatory role for Ang II on sFlt-1 expression in murine and human pregnancy and suggest that elevated sFlt-1 levels in preeclampsia may be caused by a dysregulation of the local renin/angiotensin system
Role of protein kinase C in renal vasoconstriction caused by angiotensin II
No full textIn this study we have examined the subcellar pathways along which angiotensin II (ANG II) causes renal vasoconstriction. Using the isolated perfused rat kidney model, we found that renal vasoconstriction produced by ANG II (100 pM) was not altered by the calmodulin antagonists calmidazolium (1 microM) and N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide (W-7, 10 microM) but was blunted by staurosporine (100 nM) and 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7, 50 microM), two structurally distinct putative protein kinase C inhibitors. The phorbol ester 4 alpha-phorbol 12,13-didecanoate (1-100 nM) did not alter renal vascular resistance, whereas phorbol 12-myristate 13-acetate (PMA, 1-100 nM) caused potent and dose-dependent vasoconstriction that was prevented by staurosporine (100 nM) and H-7 (50 microM). The vasoconstrictory effects of ANG II and PMA were attenuated by the calcium channel blockers verapamil (5 microM) and nifedipine (5 microM) and were reversibly inhibited when cobaltous chloride (2 mM) was added to the perfusate. Taken together, our findings support the concept that the renal vasoconstrictory effect of ANG II is essentially mediated by protein kinase C activation, which either requires or enhances the entrance of extracellular calcium
Apoptosis dependiente de angiotensina II en fibroblastos cardiacos que sobrexpresan el receptor AT1 : partipación de fosfolipasa C y proteinakinasa C
No full textLos fibroblastos cardiacos son los mayores responsables de la secreción y renovación de la matriz extracelular (MEC). Por otro lado, bajo condiciones patológicas como en el post-infarto al miocardio, los fibroblastos cardiacos se diferencian a miofibroblastos, células con un fenotipo mucho más activo en cuanto a la producción de la MEC, además ambos elementos celulares son claves en el desarrollo del remodelamiento cardiaco después de un infarto agudo al miocardio. Una regulación controlada en el crecimiento de la población de fibroblastos y miofibroblastos es importante para una correcta cicatrización y mantención de la función cardiaca.
Uno de los mayores reguladores de la población cardiaca es el Sistema Renina-Angiotensina (RAS) y se ha reportado que en una situación post-infarto este sistema se encuentra sobre-activado, específicamente la enzima convertidora de angiotensina y el receptor subtipo AT1 de angiotensina (AT1R). Nuestro modelo experimental consideró sobrexpresar el AT1R en ambos tipos celulares con el uso de adenovirus y evaluar si angiotensina II (Ang II) modula la viabilidad celular. Nuestros resultados demuestran que la estimulación con Ang II conduce a una masiva muerte del fibroblasto cardiaco neonato que sobrexpresa el AT1R (FCN-AdAT1R) de una manera tiempo-dependiente. Ang II gatilla la apoptosis por la vía mitocondrial, promoviendo el aumento de los niveles de Bax, la pérdida del potencial de membrana mitocondrial (mΔψ) y la fragmentación de la caspasa 3. Los efectos producidos por Ang II sobre los FCN-AdAT1R fueron bloqueados por Losartan (antagonista específico AT1R) y por los inhibidores de la vía de la fosfolipasa C -proteínakinasa C (PLC-PKC), U73122 y Gö6976, respectivamente. Por otra parte, los miofibroblastos cardiacos neonatos que sobrexpresan el AT1R (MCN-AdAT1R), fueron menos propensos que los FCN-AdAT1R a los efectos inducidos por Ang II, en cuanto a muerte celular, apoptosis y aumentos en los niveles de Bax. La diferente sensibilidad a la apoptosis producida por Ang II por parte de los MCN-AdAT1R se debió en parte al cambio del fenotipo celular
Nuestros resultados demuestran que Ang II ocasiona apoptosis del FCN-AdAT1R por la vía AT1R-PLC-PKC y que esta depende de la vía mitocondrialThe cardiac fibroblasts are main cells involved in secretion and turnover to extracellular
matrix protein (ECM). Under pathological conditions characterized by inflammation, as in
myocardial infarction, they are differentiated to cardiac myofibroblast, which are cells with
a more active phenotype, producing higher ECM protein. Both cellular types are key
elements in the development of cardiac remodeling after myocardial infarction. A tight
regulation of fibroblast and myofibroblast growth is important to correct wound healing and
maintain cardiac function.
Renine-angiotensin-system (RAS) is the most important regulator of cardiovascular
system, and have been reported that after myocardiac infarction the RAS is up-regulated,
specifically angiotensin converting enzyme (ACE) and angiotensin type 1 receptor (AT1R).
In our experimental model using adenovirus to overexpress the AT1R in cardiac fibroblast
(FCN-AT1R), we evaluated the Ang II effects on cell viability. Ours results show that Ang II
triggers FCN-AdAT1R death, in a time-dependent manner. The death cell produced for
Ang II in our model was apoptosis by mitochondrial pathway, through an increase Bax
expression, loss of mitochondrial membrane potential (mΔψ) and caspase 3 activation.
These effects were blocked by Losartan (specific antagonist of AT1R) and by
phospholipase C-proteinkinase C (PLC-PKC) inhibitors, U73122 and Gö6976 respectively.
For other hand, cardiac myofibroblast that overespressing AT1R (MCN-AdAT1R) were
less sensible than FCN-AdAT1R to effect of Ang II on death cell, apoptosis and expression
of Bax. The different sensibility to apoptosis Ang II-induced was due to the different
phenotype.
Ours results show that Ang II triggers apoptosis of FCN-AdAT1R by AT1R-PLC-PKC
pathway through mitochondrial disruptionVersión original del auto
Long-run pass-through from the exchange rate to import prices in African countries
No full textThis paper investigates the extent of pass-through from the nominal exchange rate to import prices for a sample of nineteen African countries. The methodology is based on panel data cointegration testing. Using annual data extending back to 1971, long-run pass-through can be best described as a fairly balanced combination of local-currency and producer-currency pricing. However, this paper offers additional insight from a moving window approach that indicates declining long-run pass-through, accompanied by decreasing inflation, occurring since the mid-1990s
COVID-19 consequences on motivational functioning: an ecological investigation of the role of momentary gustative-olfactory sensitivity and tonic heart rate variability
No full textBackground: Deficits in motivational functioning, including impairments in reward learning or reward sensitivity, are common in psychiatric disorders characterized by anhedonia, as in case of depression [1]. This transdiagnostic construct has been defined as the inability to experience pleasure in previously rewarding activities and stimuli and has been repeatedly associated with lower levels of tonic Heart Rate Variability (HRV), a measure of vagal modulation of the heart [2]. Anhedonia and depressive symptoms have been exacerbated by Coronavirus disease 2019 (COVID-19) pandemic in the general population. In line with previous evidence which report gustatory and olfactory disturbances (i.e., hyposensitivity) in psychopathological conditions particularly characterized by anhedonic symptoms, as for depression [3], the present study examined whether anosmia and ageusia (respectively defined as loss of smell and loss of taste sensitivity) two key consequences of Coronavirus disease 2019, could predict anhedonia.
Methods: 114 healthy individuals (81 females) filled out a series of self-report scales assessing indices of psychological well-being (i.e., depression, anxiety, and stress; anticipatory and consummatory pleasure) and an experiential questionnaire investigating dispositional smell and taste sensitivity, followed by a laboratory session in which resting Heart Rate Variability (as a potential predictor of anhedonic behavior) was assessed and they were asked to perform the Probabilistic Reward Task (PRT) [4]. The Probabilistic Reward Task is a well-validated signal-detection task reflecting participants’ reward-related functioning and is considered a proxy of anhedonic behavior [5]. Task performance, operationalized by response bias (i.e., a measure of systematic preference to choose the most frequently rewarded stimulus) provides an objective measure of the ability to modulate adaptive behavior as a function of reinforcement history. The research protocol ended with a 4-days ecological momentary assessment of daily ratings of smell and taste sensitivity to food.
Results: Multilevel analyses highlighted that lower tonic Heart Rate Variability (ß = .28; p < .001) and lower stable (trait-like) levels of smell and taste sensitivity (ß = .22; p < .05) independently and simultaneously predicted impaired performance on the Probabilistic Reward Task. Moreover, tonic Heart Rate Variability was not significantly associated with the trait-like common component of taste and smell sensitivity.
Conclusions: The main strength of the study is the implementation of an ecological momentary assessment design to assess taste and smell sensitivity. Moreover, to our knowledge, this is the first study showing the association between resting Heart Rate Variability and performance on an objective task assessing anhedonic behavior such as the Probabilistic Reward Task. Considering that Heart Rate Variability represented a predictor of resilience during pandemic, as well as for psychopathology in general, and that ageusia and anosmia are two of the most frequent and relevant COVID-19 symptoms, the present study provides insight into the general worldwide exacerbation of mental health issues due to COVID-19 pandemic.
References
[1] Der-Avakian, A., Pizzagalli, D.A., 2018. Translational assessments of reward and anhedonia: A tribute to Athina Markou. Biol. Psychiatry 83(11), 932–939. [2] Vazquez, L., Blood, J.D., Wu, J., Chaplin, T.M., Hommer, R.E., Rutherford, H.J., Potenza, M.N., Mayes, L.C., Crowley, M.J., 2016. High frequency heart-rate variability predicts adolescent depressive symptoms, particularly anhedonia, across one year. J. Affect. Disord. 196, 243–247. [3] Hur, K., Choi, J.S., Zheng, M., Shen, J., Wrobel, B., 2018. Association of alterations in smell and taste with depression in older adults. Laryngoscope Investig. Otolaryngol. 3(2), 94–99 [4] Pizzagalli, D.A., Jahn, A.L., O'Shea, J.P., 2005. Toward an objective characterization of an anhedonic phenotype: a signal-detection approach. Biol. Psychiatry 57(4), 319–327. [5] Insel, T., Cuthbert, B., Garvey, M., Heinssen, R., Pine, D. S., Quinn, K., Sanislow, C., Wang, P., 2010. Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders. Am. J. Psychiatry 167(7), 748–751
AT2 receptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain
No full textThe functional role of AT 2 receptors is unclear and it activates unconventional signaling pathways, which in general do not involve a classical activation of a G-protein. In the present study, we aimed to investigate the transduction mechanism of AT 2 Ang II receptors in PND15 rat hindbrain membrane preparations, which represents a physiological developmental condition. To determine whether Ang II AT 2 receptors induced association to SHP-1 in rat hindbrain, co-immunoprecipitation assays were performed. Stimulation of Ang II AT 2 receptors induced both a transient tyr-phosphorylation and activation of SHP-1. The possible participation of c-Src in Ang II-mediated SHP-1 activation, we demonstrated by recruitment of c-Src in immunocomplexes obtained with anti AT 2 or anti-SHP-1 antibodies. The association of SHP-1 to c-Src was inhibited by PD123319 and the c-Src inhibitor PP2. Similarly, SHP-1 activity determined in AT 2-immunocomplexes was inhibited by PD123319 and the c-Src inhibitor PP2. Following stimulation with Ang II, AT 2 receptors recruit c-Src, which was responsible for SHP-1 tyr-phosphorylation and activation. Since AT 2 receptors are involved in neuron migration, we tested the presence of FAK in immunocomplexes. Surprisingly, AT 2-immunocomplexes contained mainly the 85 kDa fragment of FAK. Besides, p125FAK associated to SHP-1. In summary, we demonstrated the presence of an active signal transduction mechanism in PND15 rat hindbrain, a developmental stage critical for cerebellar development. In this model, we showed a complex containing AT 2/SHP-1/c-Src/p85FAK, suggesting a potential role of Ang II AT 2 receptors in cerebellar development and neuronal differentiation.Fil: Seguin, Leonardo Roque. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Villarreal, Rodrigo Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Ciuffo, Gladys Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin
Superconducting HgBa2CaCu2Oy thin films growth on NdGaO3, SrTiO3, LaAlO3 and Y-ZrO2 substrates
No full textSuperconducting HgBa2CaCu2Oy (Hg-1212) films have been fabricated on (110) NdGaO3, (100) SrTiO3, (100) LaAlO3 and (100) Y-ZrO2 substrates by a two-step process. Good reproducible superconducting properties, zero resistance temperatures (T-c) > 115 K and critical current density (J(c)) > 4000 MA/m(2) at 77 K in zero field, are obtained. X-ray diffraction patterns indicate that the films have an epitaxial structure with the c-axis perpendicular to the surface. Scanning electron microscopy measurements show a layered growth structure with square and octagonal grains on the Hg-1212 film surfaces. (110) NdGaO3 is demonstrated to be a good substrate for growing the Hg-cuprate thin films. A lower superconducting transition temperature is observed in films deposited on Y-ZrO2 substrates, which can be attributed to variations of the microstructure in the films. (C) 1999 Elsevier Science B.V. All rights reserved.Physics, AppliedSCI(E)EI18ARTICLE3-4197-20131
The Nuisance Midges (Diptera: Chironomidae) Of Singapore'S Pandan And Bedok Reservoirs
No full textCranston, P. S., Ang, Y. C., Heyzer, A., Lim, R. B. H., Wong, W. H. (2013): The Nuisance Midges (Diptera: Chironomidae) Of Singapore'S Pandan And Bedok Reservoirs. Raffles Bulletin of Zoology 61 (2): 779-793, DOI: 10.5281/zenodo.535304
PID control system analysis, design, and technology
No full textDesigning and tuning a proportional-integral-derivative
(PID) controller appears to be conceptually intuitive, but can
be hard in practice, if multiple (and often conflicting) objectives
such as short transient and high stability are to be achieved.
Usually, initial designs obtained by all means need to be adjusted
repeatedly through computer simulations until the closed-loop
system performs or compromises as desired. This stimulates
the development of "intelligent" tools that can assist engineers
to achieve the best overall PID control for the entire operating
envelope. This development has further led to the incorporation
of some advanced tuning algorithms into PID hardware modules.
Corresponding to these developments, this paper presents a
modern overview of functionalities and tuning methods in patents,
software packages and commercial hardware modules. It is seen
that many PID variants have been developed in order to improve
transient performance, but standardising and modularising PID
control are desired, although challenging. The inclusion of system
identification and "intelligent" techniques in software based PID
systems helps automate the entire design and tuning process to
a useful degree. This should also assist future development of
"plug-and-play" PID controllers that are widely applicable and
can be set up easily and operate optimally for enhanced productivity,
improved quality and reduced maintenance requirements
Hemodynamic regulation of metalloendopeptidases EC3.4; 24.15 and EC3.4; 24.16: expression and function in the vascular endothelium
No full textHemodynamic forces, namely shear stress and cyclic strain, have been well characterised as modulators of vascular endothelial function, and have been assigned an important role in the maintainence of vascular tone, haemostasis, and regulation of vascular growth and health. They exert their influence in part by effecting changes in the production and release of vasoactive compounds by the endothelium, and by effecting changes in the levels and activity of various enzymes. Thimet oligopeptidase (EC3.4.24.15, EP24.15) and neurolysin (EC3.4.24.16, EP24.15) are closely related zinc metalloendopeptidases that have been shown to be expressed and active in the vascular endothelium. Their substrates include the vasoactive peptides bradykinin and angiotensin I, which have been identified as important regulators of both blood pressure and angiogenic processes. Other related peptidases, namely endothelin converting enzyme (ECE) and angiotensin converting enzyme (ACE), have been shown to be regulated by hemodynamic forces in the vascular endothelium. As such EP24.15 and EP24.16 are likely candidates for regulation by hemodynamic forces.
In this regard we have investigated the effect of cyclic strain on the expression and activty of EP24.15 and EP24.16 in cultured bovine aortic endothelial cells (BAECs). We have shown that exposure to cyclic strain significantly increases the mRNA expression as well as both the cellular and secreted activity of both enzymes. We have demonstrated that up-regulation of both enzymes is dependent on Gi-protein mediated signalling, although with varying Gia/G(3y subunit specificity for either enzyme. Using immunocytochemistry, we have also demonstrated a strain-dependent increase in EP24.15 protein expression within the nucleus and cytoplasm in parallel with an increase in membrane associated EP 24.15
The effects of strain on the ability of BAECs in culture to cleave both Ang I, and BK in an EC24.15/EC24.16 specific manner was also studied. We observed that exposure to cyclic strain induces a significant increase in the EP24.15 specific hydrolysis of both exogenously added BK and Ang I.
The potential of the observed effects of cyclic strain on EP24.15 to effect changes in endothelial cell function were also examined. Use of the dual EP24.15/EP24.16 inhibitor, cFP-AAF-pAB, and the EP24.15 specific antisense, FLIP, was seen to significantly attenuate cyclic strain-induced endothelial cell tubule formation and migration. We also found that the effects of FLIP transfection on cyclic strain-induced endothelial cell tubule formation could be largely reversed by addition of exogenous Ang-(l-7). Taken together these results suggest that strain-induced endothelial cell angiogenesis and migration putatively involves EP24.15 cleavage of vasoactive peptide substrates
- …
