scholarly journals Activation of Orexin System Stimulates CaMKII Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanyuan Fan ◽  
Enshe Jiang ◽  
Huanjia Gao ◽  
Jeremy Bigalke ◽  
Bojun Chen ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Sympathetic Nerve ◽  
Cellular Localization ◽  
Hypothalamic Neurons ◽  
Orexin A ◽  
Sd Rats ◽  
Nerve Recordings ◽  
The Impact ◽  
Camkii Activation ◽  
Stimulation Of

Hyperactivity of the orexin system within the paraventricular nucleus (PVN) has been shown to contribute to increased sympathetic nerve activity (SNA) and blood pressure (BP) in rodent animals. However, the underlying molecular mechanisms remain unclear. Here, we test the hypothesis that orexin system activation stimulates calcium/calmodulin-dependent kinase II (CaMKII) expression and activation, and stimulation of CaMKII expressing PVN neurons increases SNA and BP. Real-time PCR and/or western blot were carried out to test the effect of orexin-A administration on CaMKII expression in the PVN of normal Sprague Dawley (SD) rats and orexin receptor 1 (OX1R) expressing PC12 cells. Immunostaining was performed to assess OX1R cellular localization in the PVN of SD rats as well as orexin-A treatment on CaMKII activation in cultured hypothalamic neurons. In vivo sympathetic nerve recordings were employed to test the impact of optogenetic stimulation of CaMKII-expressing PVN neurons on the renal SNA (RSNA) and BP. The results showed that intracerebroventricular injection of orexin-A into the SD rat increases mRNA expression of CaMKII subunits in the PVN. In addition, Orexin-A treatment increases CaMKII expression and its phosphorylation in OX1R-expressing PC12 cells. Furthermore, Orexin-A treatment increases CaMKII activation in cultured hypothalamic neurons from neonatal SD rats. Finally, optogenetic excitation of PVN CaMKII-expressing neurons results in robust increases in RSNA and BP in SD rats. Our results suggest that increased orexin system activity activates CaMKII expression in cardiovascular relevant regions, and this may be relevant to the downstream cardiovascular effects of CaMKII.

Influence of DAFS-25+polizon composition on blood and functional state of liver of steers at fattening

2020 ◽  
pp. 15-18
Author(s):  
Inna R. Kilmetova ◽  
◽  
Igor A. Rodin ◽  
Nazira I. Khayrullina ◽  
Nikolay G. Fenchenko ◽  
...  
Keyword(s):  
Functional State ◽  
White Blood Cells ◽  
Live Weight ◽  
The Body ◽  
Farm Animals ◽  
Control Group ◽  
Standard Diet ◽  
The Impact ◽  
Experimental Group ◽  
Stimulation Of

Summary. The disbalanced feeding and the uneven distribution of micro- and macroelements in the environment leads to a trace element, in particular hypomelanosis. To accelerate the growth and preservation of young farm animals include in the diet of various biological additives and drugs, which include selenium. For stimulation of weight gain in the livestock industry, as well as for the prevention and treatment of pathological processes in addition to micro - and macrouse amino acids, primarily methionine. The aim of this work was to study the influence of composition of DAFS-25+Polizon on morpho-biochemical parameters of blood and functional state of the liver in fattening bulls of black-motley breed in the conditions of the Republic of Bashkortostan. Experiments using were conducted on bull-calves of black-motley breed of the properties in the properties age from 6 to 15 months. The first experimental group during the experiment was additionally given the composition of DAFS-25+Polizon at a dose of 2 mg/kg, the animals of the control group received a standard diet. To assess the impact of the composition DAFS-25+Polizon on metabolism cattle studied morphological and biochemical indicators of blood and conducted histological examination of the liver. It is established that the use of the composition of DAFS-25+Polizon at a dose of 2 mg/kg increases the number of erythrocytes and hemoglobin in the experimental group and reduces the amount of white blood cells. The serum content of total protein, phosphorus and calcium increases in the group of experimental animals. Microscopic examination of the liver revealed no changes in the structure of the organ and hepatocytes in the experimental group, whereas in the control group hemodynamic disorders and dystrophic changes in liver cells were observed. Thus, the use of the composition DAFS-25+Polizon at a dose of 2 mg/kg of live weight in fattening bulls black-and-white breed contributes to the increase of redox processes in the body, stimulation of metabolism, prevent the development of liver disorders of cellular mechanisms of metabolism, optimizes the structure of the liver, which generally provides higher productivity.

scholarly journals Modulation of outer medullary NaCl transport and oxygenation by nitric oxide and superoxide

2011 ◽  
Vol 301 (5) ◽  
pp. F979-F996 ◽  
Author(s):  
Aurélie Edwards ◽  
Anita T. Layton
Keyword(s):  
Nitric Oxide ◽  
Active Transport ◽  
Collecting Duct ◽  
Thick Ascending Limb ◽  
Outer Medulla ◽  
Nacl Transport ◽  
Complex Interactions ◽  
Medullary Thick Ascending Limb ◽  
The Impact ◽  
Stimulation Of

We expanded our region-based model of water and solute exchanges in the rat outer medulla to incorporate the transport of nitric oxide (NO) and superoxide (O2−) and to examine the impact of NO-O2− interactions on medullary thick ascending limb (mTAL) NaCl reabsorption and oxygen (O2) consumption, under both physiological and pathological conditions. Our results suggest that NaCl transport and the concentrating capacity of the outer medulla are substantially modulated by basal levels of NO and O2−. Moreover, the effect of each solute on NaCl reabsorption cannot be considered in isolation, given the feedback loops resulting from three-way interactions between O2, NO, and O2−. Notwithstanding vasoactive effects, our model predicts that in the absence of O2−-mediated stimulation of NaCl active transport, the outer medullary concentrating capacity (evaluated as the collecting duct fluid osmolality at the outer-inner medullary junction) would be ∼40% lower. Conversely, without NO-induced inhibition of NaCl active transport, the outer medullary concentrating capacity would increase by ∼70%, but only if that anaerobic metabolism can provide up to half the maximal energy requirements of the outer medulla. The model suggests that in addition to scavenging NO, O2− modulates NO levels indirectly via its stimulation of mTAL metabolism, leading to reduction of O2 as a substrate for NO. When O2− levels are raised 10-fold, as in hypertensive animals, mTAL NaCl reabsorption is significantly enhanced, even as the inefficient use of O2 exacerbates hypoxia in the outer medulla. Conversely, an increase in tubular and vascular flows is predicted to substantially reduce mTAL NaCl reabsorption. In conclusion, our model suggests that the complex interactions between NO, O2−, and O2 significantly impact the O2 balance and NaCl reabsorption in the outer medulla.

scholarly journals Modulation of Antigen Display on PapMV Nanoparticles Influences Its Immunogenicity

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 33
Author(s):  
Marie-Eve Laliberté-Gagné ◽  
Marilène Bolduc ◽  
Caroline Garneau ◽  
Santa-Mariela Olivera-Ugarte ◽  
Pierre Savard ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A ◽  
Matrix Protein ◽  
Cell Epitope ◽  
Vaccine Antigen ◽  
Vaccine Platform ◽  
Peptide Antigens ◽  
C Terminus ◽  
The Impact ◽  
Stimulation Of

Background: The papaya mosaic virus (PapMV) vaccine platform is a rod-shaped nanoparticle made of the recombinant PapMV coat protein (CP) self-assembled around a noncoding single-stranded RNA (ssRNA) template. The PapMV nanoparticle induces innate immunity through stimulation of the Toll-like receptors (TLR) 7 and 8. The display of the vaccine antigen at the surface of the nanoparticle, associated with the co-stimulation signal via TLR7/8, ensures a strong stimulation of the immune response, which is ideal for the development of candidate vaccines. In this study, we assess the impact of where the peptide antigen is fused, whether at the surface or at the extremities of the nanoparticles, on the immune response directed to that antigen. Methods: Two different peptides from influenza A virus were used as model antigens. The conserved M2e peptide, derived from the matrix protein 2 was chosen as the B-cell epitope, and a peptide derived from the nucleocapsid was chosen as the cytotoxic T lymphocytes (CTL) epitope. These peptides were coupled at two different positions on the PapMV CP, the N- (PapMV-N) or the C-terminus (PapMV-C), using the transpeptidase activity of Sortase A (SrtA). The immune responses, both humoral and CD8+ T-cell-mediated, directed to the peptide antigens in the two different fusion contexts were analyzed and compared. The impact of coupling density at the surface of the nanoparticle was also investigated. Conclusions: The results demonstrate that coupling of the peptide antigens at the N-terminus (PapMV-N) of the PapMV CP led to an enhanced immune response to the coupled peptide antigens as compared to coupling to the C-terminus. The difference between the two vaccine platforms is linked to the enhanced capacity of the PapMV-N vaccine platform to stimulate TLR7/8. We also demonstrated that the strength of the immune response increases with the density of coupling at the surface of the nanoparticles.

The New Flow Control Devices Autonomously Controlling the Performance of Matrix Acid Stimulation Operations in Carbonate Reservoirs

2021 ◽  
Author(s):  
Mojtaba Moradi ◽  
Michael R Konopczynski
Keyword(s):  
Flow Control ◽  
Dynamic Change ◽  
Injection Rate ◽  
Control Flow ◽  
Carbonate Reservoir ◽  
Operating Conditions ◽  
Carbonate Reservoirs ◽  
High Permeability ◽  
The Impact ◽  
Stimulation Of

Abstract Matrix acidizing is a common but complex stimulation treatment that could significantly improve production/injection rate, particularly in carbonate reservoirs. However, the desired improvement in all zones of the well by such operation may not be achieved due to existing and/or developing reservoir heterogeneity. This paper describes how a new flow control device (FCD) previously used to control water injection in long horizontal wells can also be used to improve the conformance of acid stimulation in carbonate reservoirs. Acid stimulation of a carbonate reservoir is a positive feedback process. Acid preferentially takes the least resistant path, an area with higher permeability or low skin. Once acid reacts with the formation, the injectivity in that zone increases, resulting in further preferential injection in the stimulated zone. Over-treating a high permeability zone results in poor distribution of acid to low permeability zones. Mechanical, chemical or foam diversions have been used to improve stimulation conformance along the wellbore, however, they may fail in carbonate reservoirs with natural fractures where fracture injectivity dominates the stimulation process. A new FCD has been developed to autonomously control flow and provide mechanical diversion during matrix stimulation. Once a predefined upper limit flowrate is reached at a zone, the valve autonomously closes. This eliminates the impact of thief zone on acid injection conformance and maintains a prescribed acid distribution. Like other FCDs, this device is installed in several compartments in the wells. The device has two operating conditions, one, as a passive outflow control valve, and two, as a barrier when the flow rate through the valve exceeds a designed limit, analogous to an electrical circuit breaker. Once a zone has been sufficiently stimulated by the acid and the injection rate in that zone exceeds the device trip point, the device in that zone closes and restricts further stimulation. Acid can then flow to and stimulate other zones This process can be repeated later in well life to re-stimulate zones. This performance enables the operators to minimise the impacts of high permeability zones on the acid conformance and to autonomously react to a dynamic change in reservoirs properties, specifically the growth of wormholes. The device can be installed as part of lower completions in both injection and production wells. It can be retrofitted in existing completions or be used in a retrievable completion. This technology allows repeat stimulation of carbonate reservoirs, providing mechanical diversion without the need for coiled tubing or other complex intervention. This paper will briefly present an overview of the device performance, flow loop testing and some results from numerical modelling. The paper also discusses the completion design workflow in carbonates reservoirs.

scholarly journals Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice

2017 ◽  
Vol 313 (6) ◽  
pp. F1243-F1253 ◽  
Author(s):  
Minolfa C. Prieto ◽  
Virginia Reverte ◽  
Mykola Mamenko ◽  
Marta Kuczeriszka ◽  
Luciana C. Veiras ◽  
...  
Keyword(s):  
Renal Function ◽  
Collecting Duct ◽  
Ang Ii ◽  
Open Probability ◽  
Sodium Transporters ◽  
Prorenin Receptor ◽  
Active Channels ◽  
The Impact ◽  
Renal Responses ◽  
Stimulation Of

Augmented intratubular angiotensin (ANG) II is a key determinant of enhanced distal Na+ reabsorption via activation of epithelial Na+ channels (ENaC) and other transporters, which leads to the development of high blood pressure (BP). In ANG II-induced hypertension, there is increased expression of the prorenin receptor (PRR) in the collecting duct (CD), which has been implicated in the stimulation of the sodium transporters and resultant hypertension. The impact of PRR deletion along the nephron on BP regulation and Na+ handling remains controversial. In the present study, we investigate the role of PRR in the regulation of renal function and BP by using a mouse model with specific deletion of PRR in the CD (CDPRR-KO). At basal conditions, CDPRR-KO mice had decreased renal function and lower systolic BP associated with higher fractional Na+ excretion and lower ANG II levels in urine. After 14 days of ANG II infusion (400 ng·kg−1·min−1), the increases in systolic BP and diastolic BP were mitigated in CDPRR-KO mice. CDPRR-KO mice had lower abundance of cleaved αENaC and γENaC, as well as lower ANG II and renin content in urine compared with wild-type mice. In isolated CD from CDPRR-KO mice, patch-clamp studies demonstrated that ANG II-dependent stimulation of ENaC activity was reduced because of fewer active channels and lower open probability. These data indicate that CD PRR contributes to renal function and BP responses during chronic ANG II infusion by enhancing renin activity, increasing ANG II, and activating ENaC in the distal nephron segments.

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