MEKK3–TGFβ crosstalk regulates inward arterial remodeling

Arterial remodeling is an important adaptive mechanism that maintains normal fluid shear stress in a variety of physiologic and pathologic conditions. Inward remodeling, a process that leads to reduction in arterial diameter, plays a critical role in progression of such common diseases as hypertension and atherosclerosis. Yet, despite its pathogenic importance, molecular mechanisms controlling inward remodeling remain undefined. Mitogen-activated protein kinases (MAPKs) perform a number of functions ranging from control of proliferation to migration and cell-fate transitions. While the MAPK ERK1/2 signaling pathway has been extensively examined in the endothelium, less is known about the role of the MEKK3/ERK5 pathway in vascular remodeling. To better define the role played by this signaling cascade, we studied the effect of endothelial-specific deletion of its key upstream MAP3K, MEKK3, in adult mice. The gene’s deletion resulted in a gradual inward remodeling of both pulmonary and systematic arteries, leading to spontaneous hypertension in both vascular circuits and accelerated progression of atherosclerosis in hyperlipidemic mice. Molecular analysis revealed activation of TGFβ-signaling both in vitro and in vivo. Endothelial-specific TGFβR1 knockout prevented inward arterial remodeling in MEKK3 endothelial knockout mice. These data point to the unexpected participation of endothelial MEKK3 in regulation of TGFβR1-Smad2/3 signaling and inward arterial remodeling in artery diseases.

EFFECT OF NANOFLUIDS ON PERFORMANCE OF SOLAR APPLIANCES: A Review

The sun is a natural source of renewable energy. The use of solar energy may be especially important within global warming and the reduction of carbon dioxide emissions. solar energy is tested using solar thermal energy, photovoltaic energy development, and so on. Solar heat is the most common use around it. For solar-powered solar collectors, plates or tubes are coated with a layer of selective immersion fabric used to soak up solar energy, after which the energy is filled with excitement with the help of an active liquid within the heat form. This type of collector presents a number of shortcomings, including rules regarding incident congestion and relatively high heat loss. Lack of fossil fuels and environmental considerations have encouraged researchers to use energy sources that include solar energy. Therefore, it is important to maximize the efficiency and replicate solar thermal systems. Continuously, a few of the aforementioned nanofluid packages for thermal energy storage, solar cells, and sun exposure are being updated. Distribution defines the values of nanoparticles in a normal fluid base has a significant impact on the visible homes and the thermo-body of the fluid base. Enhancement of solar irradiance assimilation results in better heat transfer fines followed by more efficient heat transfer. Nanofluid suspension of nanoparticles in basic liquid, a new therapeutic goal of nanotechnology has been developed. Nanofluids have unique functions of a single type from a common stable liquid mixture in which mm or µm particles of metal and non-metallic particles are dispersed. due to its amazing properties, nanofluids are widely used to improve heat transfer. The purpose of this experimental manuscript is to examine nanofluids in solar panels. To overcome those problems, a direct sun suction collector has been used to exploit the heat of the sun.

Critical care management of patients with spontaneous subarachnoid haemorrhage – a review

Spontaneous subarachnoid haemorrhage is characterized by extravasation of blood into the subarachnoid space without a preceding trauma. The leading cause is a ruptured intracranial aneurysm. Serious neurologic complications can occur, such as rebleeding, cerebral vasospasm and delayed cerebral ischemia. Subarachnoid haemorrhage is a serious condition with a high mortality rate and those who survive often suffer long-term consequences. Prevention of rebleeding by aneurysm repair is essential and guidelines recommend this procedure should be done as soon as possible or within 72 hours. Management requires intensive care with emphasis on accurate blood pressure control, maintaining normal fluid and electrolyte balance and monitoring the level of consciousness. All patients should be treated with the calcium channel blocker nimodipine to reduce the risk of vasospasm and delayed cerebral ischemia which are among the most serious complications of subarachnoid haemorrhage.

MEKK3-TGFβ crosstalk regulates inward arterial remodeling

Arterial remodeling is an important adaptive mechanism that maintains normal fluid shear stress in a variety of physiologic and pathologic conditions. Inward remodeling, a process that leads to reduction in arterial diameter, plays a critical role in progression of such common diseases as hypertension and atherosclerosis. Yet despite its pathogenic importance, molecular mechanisms controlling inward remodeling remain undefined. Mitogen-activated protein kinases (MAPKs) perform a number of functions ranging from control of proliferation to migration and cell fate transitions. While the MAPK ERK1/2 signaling pathway has been extensively examined in the endothelium, less is known about the role of the MEKK3/ERK5 pathway in vascular remodeling. To better define the role played by this signaling cascade, we studied the effect of endothelial-specific deletion of its key upstream MAP3K, MEKK3, in adult mice. The gene’s deletion resulted in a gradual inward remodeling of both pulmonary and systematic arteries leading to spontaneous hypertension in both vascular circuits and accelerated progression of atherosclerosis in hyperlipidemic mice. Molecular analysis revealed activation of TGFβ signaling both in vitro and in vivo. Endothelial-specific TGFβR1 knockout prevented inward arterial remodeling in MEKK3 endothelial knockout mice. These data point to the unexpected participation of endothelial MEKK3 in regulation of TGFβR1-Smad2/3 signaling and inward arterial remodeling in artery diseases.SignificanceInward remodeling of arteries to reduce lumen diameter is a major factor in disease progression and morbidity in multiple vascular diseases, including hypertension and atherosclerosis. However, molecular mechanisms controlling inward arterial remodeling remain largely undefined. In this study, we identify endothelial MEKK3 as an unexpected regulator of inward remodeling via inhibition of TGFβ-Smad2/3 signaling. Genetic deletion of MEKK3 in adult endothelium results in induction of TGFβ-Smad2/3 signaling, endothelial-to-mesenchymal transition and inward remodeling in both pulmonary and arterial circuits. The latter process results in pulmonary and systemic hypertension and accelerates atherosclerosis. These results provide a new basis for understanding the inward artery remodeling that leads to reduced blood flow to affected tissues and exacerbates hypertension in vascular disease.

Cognitive Assessment in GNAO1 Neurodevelopmental Disorder Using an Eye Tracking System

GNAO1 gene mutations are associated with a neurodevelopmental disorder characterized by developmental delay, epilepsy, and movement disorder. Eye tracking and eye movement analysis are an intriguing method to assess cognitive and language function and, to the best of our knowledge, it has never been tested in a standardized way in GNAO1. GNAO1 children are usually wheelchair-bound and with numerous motor constrains, including dystonic movements and postures, heterotropia, and hypotonia, making the cognitive assessment arduous. These contribute to the burden and disability, with a high level of frustration of caregivers and patients. We have herein demonstrated that, through an eye tracking system, six GNAO1 patients evaluated showed variable degrees of communicative intent through intentionally directed gaze. Moreover, three of these were able to complete a cognitive evaluation, and showed normal fluid intelligence and lexical comprehension. In conclusion, in GNAO1-related disorders, the degree of cognitive development is underestimated; eye tracking technologies may help in overcome these boundaries.

Pseudo-Laminarization of Mixed Microbubble Water and Complex Fluids in Capillary Flows

Symmetry in fluid flow is determined by external factors such as magnetic or electric fields. Owing to the electrical properties of fluids, liquids containing fine bubble or ionic surfactant molecules differ from the normal fluid flow. Therefore, the pressure drop and frictional coefficient in a pipe are measured and estimated for water alone, for mixed microbubble water (MB), and for complex fluids (anionic surfactant solution and polymer solution) in capillary flow with constant flow rate. For water alone, good agreement is obtained between the experimental and theoretical values for laminar Hagen–Poiseuille flow and the Blasius expression in turbulent flow. For the MB, pseudo-laminarization is suggested up to a Reynolds number of 4.2×103. Both the anionic surfactant solution and the polymer solution exhibit the same tendency as that of the MB. In explaining these behaviors, elasticity and electrical interaction are discussed, and electrical interaction on the capillary wall is strongly suggested to be a contributing factor. Additionally, surface tension is investigated and supports the discussion.

Increased angiotensin II formation in the brain modulates cardiovascular homeostasis and erythropoiesis

In spite of the fact that the modulatory effects of angiotensin II (Ang II) on the sympathetic nerve activity to targeted organs involved in blood pressure (BP) regulation is well acknowledged, the local production of this peptide in the brain and the consequences of enhanced central Ang II beyond the cardiovascular system are not yet well comprehended. In this study, we generated and validated a new transgenic mouse line overexpressing the rat full-length angiotensinogen (Agt) protein specifically in the brain (Agt-Tg). Adult Agt-Tg mice presented overall increased gene expression of total Agt in the brain including brainstem and hypothalamus. In addition, the excess of Agt led to abundantly detectable brain Ang II levels as well as increased circulating copeptin levels. Agt-Tg displayed raised BP in acute recordings, while long-term telemetrically measured basal BP was indistinguishable from wildtypes. Agt-Tg has altered peripheral renin angiotensin system and vasomotor sympathetic tone homeostasis, because renal gene expression analysis, plasma Ang II measurements and ganglionic blockade experiments revealed suppressed renin expression, reduced Ang II and higher neurogenic pressure response, respectively. Plasma and urine screens revealed apparently normal fluid and electrolyte handling in Agt-Tg. Interestingly, hematological analyses showed increased hematocrit in Agt-Tg caused by enhanced erythropoiesis, which was reverted by submitting the transgenic mice to a long-term peripheral sympathectomy protocol. Collectively, our findings suggest that Agt-Tg is a valuable tool not only to study brain Ang II formation and its modulatory effects on cardiovascular homeostasis but also its role in erythropoiesis control via autonomic modulation.

Anomalous normal fluid response in a chiral superconductor UTe2

Chiral superconductors have been proposed as one pathway to realize Majorana normal fluid at its boundary. However, the long-sought 2D and 3D chiral superconductors with edge and surface Majorana normal fluid are yet to be conclusively found. Here, we report evidence for a chiral spin-triplet pairing state of UTe2 with surface normal fluid response. The microwave surface impedance of the UTe2 crystal was measured and converted to complex conductivity, which is sensitive to both normal and superfluid responses. The anomalous residual normal fluid conductivity supports the presence of a significant normal fluid response. The superfluid conductivity follows the temperature behavior predicted for an axial spin-triplet state, which is further narrowed down to a chiral spin-triplet state with evidence of broken time-reversal symmetry. Further analysis excludes trivial origins for the observed normal fluid response. Our findings suggest that UTe2 can be a new platform to study exotic topological excitations in higher dimension.