Sestrin proteins have been implicated in multiple biological processes including resistance to oxidative and genotoxic stresses, protection against aging-related pathologies, and promotion of ...metabolic homeostasis; however, the underlying mechanisms are incompletely understood. Some evidence suggests that sestrins may inhibit mTORC1 (mechanistic target of rapamycin complex 1) through inhibition of RagA/B GTPases or activation of AMPK; however, whether sestrins are also involved in mTORC2 regulation and function is unclear. To investigate the functions and mechanisms of Sestrin 3 (Sesn3), we generated Sesn3 liver-specific transgenic and knockout mice. Our data show that Sesn3 liver-specific knockout mice exhibit insulin resistance and glucose intolerance, and Sesn3 transgenic mice were protected against insulin resistance induced by a high-fat diet. Using AMPK liver-specific knockout mice, we demonstrate that the Sesn3 insulin-sensitizing effect is largely independent of AMPK. Biochemical analysis reveals that Sesn3 interacts with and activates mTORC2 and subsequently stimulates Akt phosphorylation at Ser473. These findings suggest that Sesn3 can activate Akt via mTORC2 to regulate hepatic insulin sensitivity and glucose metabolism.
Elevated LDL-cholesterol is a risk factor for the development of cardiovascular disease. Thus, proper control of LDL-cholesterol homeostasis is critical for organismal health. Genetic analysis has ...identified PCSK9 (proprotein convertase subtilisin/kexin type 9) as a crucial gene in the regulation of LDL-cholesterol via control of LDL receptor degradation. Although biochemical characteristics and clinical implications of PCSK9 have been extensively investigated, epigenetic regulation of this gene is largely unknown. In this work we have discovered that Sirt6, an NAD+-dependent histone deacetylase, plays a critical role in the regulation of the Pcsk9 gene expression in mice. Hepatic Sirt6 deficiency leads to elevated Pcsk9 gene expression and LDL-cholesterol as well. Mechanistically, we have demonstrated that Sirt6 can be recruited by forkhead transcription factor FoxO3 to the proximal promoter region of the Pcsk9 gene and deacetylates histone H3 at lysines 9 and 56, thereby suppressing the gene expression. Also remarkably, overexpression of Sirt6 in high fat diet-fed mice lowers LDL-cholesterol. Overall, our data suggest that FoxO3 and Sirt6, two longevity genes, can reduce LDL-cholesterol levels through regulation of the Pcsk9 gene.
Background: PCSK9 is critical for LDL-cholesterol regulation, but the epigenetic regulation of the PCSK9 gene is not clear.
Results: FoxO3 and Sirt6 suppress the PCSK9 gene expression and reduce LDL-cholesterol.
Conclusion: Hepatic FoxO3 and Sirt6 control LDL-cholesterol homeostasis.
Significance: FoxO3 and Sirt6 are important for cardiovascular health.
SIRT6 is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis and anti-inflammation. However, its function in the adipose tissue ...is not well understood. To examine the metabolic function of SIRT6 in the adipose tissue, we generated two mouse models that are deficient in Sirt6 using the Cre-lox approach. Two commonly used Cre lines that are driven by either the mouse Fabp4 or Adipoq gene promoter were chosen for this study. The Sirt6-knockout mice generated by the Fabp4-Cre line (Sirt6f/f:Fabp4-Cre) had a significant increase in both body weight and fat mass and exhibited glucose intolerance and insulin resistance as compared with the control wild-type mice. At the molecular levels, the Sirt6f/f:Fabp4-Cre-knockout mice had increased expression of inflammatory genes including F4/80, TNFα, IL-6 and MCP-1 in both white and brown adipose tissues. Moreover, the knockout mice showed decreased expression of the adiponectin gene in the white adipose tissue and UCP1 in the brown adipose tissue, respectively. In contrast, the Sirt6 knockout mice generated by the Adipoq-Cre line (Sirt6f/f:Adipoq-Cre) only had modest insulin resistance. In conclusion, our data suggest that the function of SIRT6 in the Fabp4-Cre-expressing cells in addition to mature adipocytes plays a critical role in body weight maintenance and metabolic homeostasis.
Self-sustained vibrations in systems ranging from lasers to clocks to biological systems are often associated with the coefficient of linear friction, which relates the friction force to the ...velocity, becoming negative. The runaway of the vibration amplitude is prevented by positive nonlinear friction that increases rapidly with the amplitude. Here we use a modulated electromechanical resonator to show that nonlinear friction can be made negative and sufficiently strong to overcome positive linear friction at large vibration amplitudes. The experiment involves applying a drive that simultaneously excites two phonons of the studied mode and a phonon of a faster decaying high-frequency mode. We study generic features of the oscillator dynamics with negative nonlinear friction. Remarkably, self-sustained vibrations of the oscillator require activation in this case. When, in addition, a resonant force is applied, a branch of large-amplitude forced vibrations can emerge, isolated from the branch of the ordinary small-amplitude response.
Ring Current Morphology From MMS Observations Tan, X.; Dunlop, M. W.; Dong, X.‐C. ...
Journal of geophysical research. Space physics,
April 2023, 2023-04-00, 20230401, Letnik:
128, Številka:
4
Journal Article
Recenzirano
Odprti dostop
We directly estimate the in situ current density of the Earth’s ring current (RC) using the curlometer method and investigate its morphology using the small spatial separations and high accuracy of ...the Magnetospheric Multiscale mission. Through statistical analysis of data from September 2015 to the end of 2016, covering the region of 2–8 RE (Earth radius, 6,371 km), we reveal an almost complete near‐equatorial (within ±20° $\pm 20{}^{\circ}$) RC morphology in terms of radial distance and magnetic local time (MLT) which complements and extends that found from previous studies. We found no evidence of RC enhancement on the dusk side during geomagnetic active periods, but details of MLT asymmetries in, and the boundary between, the inner (eastward) and outer (westward) currents are revealed. We propose that part of the asymmetry demonstrated here suggests that in addition to the overall persistence of the westward RC, two large banana‐like currents are directly observed, one which could arise from a peak of plasma pressure near ∼4.8 RE on the noon side and the other from a valley of plasma pressure which could arise near ∼4.8 RE on the night side.
Plain Language Summary
Large‐scale current systems existing in space affect the magnetic field on the surface of Earth and the ring current has a dominant influence. Space weather drives large variations in these currents which disturb the surface magnetic fields. When the disturbance is violent, it is called a magnetic storm and may have a disastrous impact on satellite and ground systems. Using the high‐precision magnetic field data of the four spacecraft in NASA’s Magnetospheric Multiscale mission, by employing a multispacecraft analysis method, we calculate the distribution of local current density in space. Through statistical analysis of the current in the region, we study its morphology. We confirm the asymmetry of the ring current found in previous studies and suggest a new explanation for part of the asymmetry, that is, that the generally westward ring current is superimposed on closed, banana‐like currents.
Key Points
General trends of ring current morphology are revealed by statistical analysis of current density, directly calculated from multispacecraft analysis of Magnetospheric Multiscale mission data
Banana‐like currents (at both inner and outer L‐shells) are directly observed, resulting in both day–night and dawn–dusk asymmetry
Although an inner asymmetric eastward current is confirmed, no westward dusk‐side, storm time, ring current enhancement is observed
Hyperglycemia has detrimental effects on normal organ functions in people with diabetes, chiefly contributing to the development of diabetic complications in both central and peripheral organs. ...Hyperglycemia, a hallmark of diabetes, results from dysregulation of both glucose intake/production and uptake/utilization. In type 1 diabetes, due to pancreatic β-cell death and insulin deficiency, glucose uptake and disposal decrease significantly while endogenous glucose production increases. In type 2 diabetes, due to insulin resistance and impaired insulin secretion, glucose homeostasis is similarly dysregulated. With regard to the endogenous glucose production, there are two metabolic processes-gluconeogenesis and glycogenolysis. The liver is the major organ responsible for both processes. Thus, the control of hepatic glucose production is highly relevant to the treatment of both type 1 and type 2 diabetes. Here, Dong discusses identification of SCP4 as a key nuclear phosphatase for Forkhead box O transcription factors should help people better understand the dynamics of checks and balances of these critical mediators in the insulin signaling pathway.
Acori Tatarinowii Rhizome (ATR; the dried rhizome of Acori tatarinowii Schott) is a well-known herb being used for mental disorder in China and Asia. Volatile oil is considered as the active ...ingredient of ATR, and asarones account for more than 90% of total volatile oil. Here, the protective effects of ATR oil and asarones, both α-asarone and β-asarone, were probed in cultured rat astrocytes. The cyto-protective effect of ATR oil and asarones against tBHP-induced astrocyte injury was revealed, and additionally ATR oil and asarones reduced the tBHP-induced intracellular reactive oxygen species (ROS) accumulation. In parallel, the activity of anti-oxidant response element (ARE) promoter construct (pARE-Luc), being transfected in cultured astrocytes, was markedly induced by application of ATR oil and asarones. The mRNAs encoding anti-oxidant enzymes, e.g. glutathione S-transferase (GST), glutamate-cysteine ligase modulatory subunit (GCLM), glutamate-cysteine ligase catalytic subunit (GCLC) and NAD(P)H quinone oxidoreductase (NQO1) were induced by ATR oil and asarones in a dose-dependent manner. The ATR oil/asarone-induced gene expression could be mediated by Akt phosphorylation; because the applied LY294002, a phosphoinositide 3-kinase inhibitor, fully abolished the induction. These results demonstrated that α-asarone and β-asarone could account, at least partly, the function of ATR being a Chinese medicinal herb.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report an empirical thermodynamic law for the synthesis of core/shell metal/heterogeneous oxide nanocapsules, such as Fe/SiO2, Ni/SiO2, Fe/B2O3, Ni/B2O3, Fe/Al2O3, Fe/MnO2, Fe/Y2O3, Fe/CeO2, and ...Fe/La2O3, by arc-discharge evaporating a compressed mixture of Fe (or Ni) powders and the oxide powders of shell components. By integrating such dielectric oxide shells and magnetic metal cores in each particle, the electromagnetic losses can be artificially manipulated at the whole S-band, C-band, X-band, and Ku frequency ranges. The microscopic origins of the controllability of electromagnetic losses are ascribed to the specific matching and interfacial coupling between the magnetic cores and dielectric shells.
The Lhasa terrane in southern Tibet is composed of Precambrian crystalline basement, Paleozoic to Mesozoic sedimentary strata and Paleozoic to Cenozoic magmatic rocks. This terrane has long been ...accepted as the last crustal block to be accreted with Eurasia prior to its collision with the northward drifting Indian continent in the Cenozoic. Thus, the Lhasa terrane is the key for revealing the origin and evolutionary history of the Himalayan–Tibetan orogen. Although previous models on the tectonic development of the orogen have much evidence from the Lhasa terrane, the metamorphic history of this terrane was rarely considered. This paper provides an overview of the temporal and spatial characteristics of metamorphism in the Lhasa terrane based mostly on the recent results from our group, and evaluates the geodynamic settings and tectonic significance. The Lhasa terrane experienced multistage metamorphism, including the Neoproterozoic and Late Paleozoic HP metamorphism in the oceanic subduction realm, the Early Paleozoic and Early Mesozoic MP metamorphism in the continent–continent collisional zone, the Late Cretaceous HT/MP metamorphism in the mid-oceanic ridge subduction zone, and two stages of Cenozoic MP metamorphism in the thickened crust above the continental subduction zone. These metamorphic and associated magmatic events reveal that the Lhasa terrane experienced a complex tectonic evolution from the Neoproterozoic to Cenozoic. The main conclusions arising from our synthesis are as follows: (1) The Lhasa block consists of the North and South Lhasa terranes, separated by the Paleo-Tethys Ocean and the subsequent Late Paleozoic suture zone. (2) The crystalline basement of the North Lhasa terrane includes Neoproterozoic oceanic crustal rocks, representing probably the remnants of the Mozambique Ocean derived from the break-up of the Rodinia supercontinent. (3) The oceanic crustal basement of North Lhasa witnessed a Late Cryogenian (~650Ma) HP metamorphism and an Early Paleozoic (~485Ma) MP metamorphism in the subduction realm associated with the closure of the Mozambique Ocean and the final amalgamation of Eastern and Western Gondwana, suggesting that the North Lhasa terrane might have been partly derived from the northern segment of the East African Orogen. (4) The northern margin of Indian continent, including the North and South Lhasa, and Qiangtang terranes, experienced Early Paleozoic magmatism, indicating an Andean-type orogeny that resulted from the subduction of the Proto-Tethys Ocean after the final amalgamation of Gondwana. (5) The Lhasa and Qiangtang terranes witnessed Middle Paleozoic (~360Ma) magmatism, suggesting an Andean-type orogeny derived from the subduction of the Paleo-Tethys Ocean. (6) The closure of Paleo-Tethys Ocean between the North and South Lhasa terranes and subsequent terrane collision resulted in the formation of Late Permian (~260Ma) HP metamorphic belt and Triassic (220Ma) MP metamorphic belt. (7) The South Lhasa terrane experienced Late Cretaceous (~90Ma) Andean-type orogeny, characterized by the regional HT/MP metamorphism and coeval intrusion of the voluminous Gangdese batholith during the northward subduction of the Neo-Tethyan Ocean. (8) During the Early Cenozoic (55–45Ma), the continent–continent collisional orogeny has led to the thickened crust of the South Lhasa terrane experiencing MP amphibolite-facies metamorphism and syn-collisional magmatism. (9) Following the continuous continent convergence, the South Lhasa terrane also experienced MP metamorphism during Late Eocene (40–30Ma). (10) During Mesozoic and Cenozoic, two different stages of paired metamorphic belts were formed in the oceanic or continental subduction zones and the middle and lower crust of the hanging wall of the subduction zone. The tectonic imprints from the Lhasa terrane provide excellent examples for understanding metamorphic processes and geodynamics at convergent plate boundaries.
Display omitted
► The Lhasa terrane experienced multistage and multiple types of metamorphism; ► The North Lhasa terrane witnessed a Neoproterozoic HP metamorphism; ► The North and South Lhasa terranes were separated by a Late Permian HP metamorphic belt. ► The South Lhasa terrane witnessed Late Cretaceous HT/MP to Eocene MP metamorphism. ► The Lhasa terranes experienced multistage orogenesis from the Neoproterozoic to Cenozoic.
Curlometer Technique and Applications Dunlop, M. W.; Dong, X.‐C.; Wang, T.‐Y. ...
Journal of geophysical research. Space physics,
November 2021, 2021-11-00, 20211101, 2021-11, Letnik:
126, Številka:
11
Journal Article
Recenzirano
Odprti dostop
We review the range of applications and use of the curlometer, initially developed to analyze Cluster multi‐spacecraft magnetic field data; but more recently adapted to other arrays of spacecraft ...flying in formation, such as MMS small‐scale, 4‐spacecraft configurations; THEMIS close constellations of 3–5 spacecraft, and Swarm 2–3 spacecraft configurations. Although magnetic gradients require knowledge of spacecraft separations and the magnetic field, the structure of the electric current density (for example, its relative spatial scale), and any temporal evolution, limits measurement accuracy. Nevertheless, in many magnetospheric regions the curlometer is reliable (within certain limits), particularly under conditions of time stationarity, or with supporting information on morphology (for example, when the geometry of the large scale structure is expected). A number of large‐scale regions have been covered, such as: the cross‐tail current sheet, ring current, the current layer at the magnetopause and field‐aligned currents. Transient and smaller scale current structures (e.g., reconnected flux tube or dipolarisation fronts) and energy transfer processes. The method is able to provide estimates of single components of the vector current density, even if there are only two or three satellites flying in formation, within the current region, as can be the case when there is a highly irregular spacecraft configuration. The computation of magnetic field gradients and topology in general includes magnetic rotation analysis and various least squares approaches, as well as the curlometer, and indeed the added inclusion of plasma measurements and the extension to larger arrays of spacecraft have recently been considered.
Plain Language Summary
This article is an account of the curlometer method which was designed to estimate the electric current density from measurements of the magnetic field taken on board the four Cluster II spacecraft. It has been used very extensively in many regions of the magnetosphere, and has been applied to data from other spacecraft. The technique is robust and is known to be stable under certain conditions. It has also been integrated into other techniques dealing with the geometry of the magnetic field and its gradients in space.
Key Points
Robust multi‐spacecraft analysis method using the magnetic field
Allows the estimate of the vector electric current density directly
Has been applied widely in many regions of the magnetosphere
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