Serjania erecta
Raldk is an essential genetic resource due to its anti-inflammatory, gastric protection, and anti-Alzheimer properties. However, the genetic and evolutionary aspects of the species ...remain poorly known. Here, we sequenced and assembled the complete chloroplast genome of
S. erecta
and used it in a comparative analysis within the Sapindaceae family.
S. erecta
has a chloroplast genome (cpDNA) of 159,297 bp, divided into a Large Single Copy region (LSC) of 84,556 bp and a Small Single Copy region (SSC) of 18,057 bp that are surrounded by two Inverted Repeat regions (IRa and IRb) of 28,342 bp. Among the 12 species used in the comparative analysis,
S. erecta
has the fewest long and microsatellite repeats. The genome structure of Sapindaceae species is relatively conserved; the number of genes varies from 128 to 132 genes, and this variation is associated with three main factors: (1) Expansion and retraction events in the size of the IRs, resulting in variations in the number of
rpl22
,
rps19
, and
rps3
genes; (2) Pseudogenization of the
rps2
gene; and (3) Loss or duplication of genes encoding tRNAs, associated with the duplication of
trnH-GUG
in
X. sorbifolium
and the absence of
trnT-CGU
in the Dodonaeoideae subfamily. We identified 10 and 11 mutational hotspots for Sapindaceae and Sapindoideae, respectively, and identified six highly diverse regions (
tRNA-Lys — rps16, ndhC – tRNA-Val, petA – psbJ, ndhF, rpl32 – ccsA
, and
ycf1
) are found in both groups, which show potential for the development of DNA barcode markers for molecular taxonomic identification of
Serjania
. We identified that the
psaI
gene evolves under neutrality in Sapindaceae, while all other chloroplast genes are under strong negative selection. However, local positive selection exists in the
ndhF
,
rpoC2
,
ycf1
, and
ycf2
genes. The genes
ndhF
and
ycf1
also present high nucleotide diversity and local positive selection, demonstrating significant potential as markers. Our findings include providing the first chloroplast genome of a member of the Paullinieae tribe. Furthermore, we identified patterns in variations in the number of genes and selection in genes possibly associated with the family’s evolutionary history.
Abstract The aim of this study was to determine whether endogenous GLUT1 induction and the increased glucose utilization that accompanies pressure overload hypertrophy (POH) are required to maintain ...cardiac function during hemodynamic stress, and to test the hypothesis that lack of GLUT1 will accelerate the transition to heart failure. To determine the contribution of endogenous GLUT1 to the cardiac adaptation to POH, male mice with cardiomyocyte-restricted deletion of the GLUT1 gene (G1KO) and their littermate controls (Cont) were subjected to transverse aortic constriction (TAC). GLUT1 deficiency reduced glycolysis and glucose oxidation by 50%, which was associated with a reciprocal increase in fatty acid oxidation (FAO) relative to controls. Four weeks after TAC, glycolysis increased and FAO decreased by 50% in controls, but were unchanged in G1KO hearts relative to shams. G1KO and controls exhibited equivalent degrees of cardiac hypertrophy, fibrosis, and capillary density loss after TAC. Following TAC, in vivo left ventricular developed pressure was decreased in G1KO hearts relative to controls, but + dP/dt was equivalently reduced in Cont and G1KO mice. Mitochondrial function was equivalently impaired following TAC in both Cont and G1KO hearts. GLUT1 deficiency in cardiomyocytes alters myocardial substrate utilization, but does not substantially exacerbate pressure-overload induced contractile dysfunction or accelerate the progression to heart failure.
Summary
The application of modular multilevel converters (MMC) in medium voltage static synchronous compensators (STATCOMs) has been investigated in recent years. A huge challenge for MMC‐STATCOM is ...to compute the gain of the controllers. Therefore, the contribution of this paper is the proposal of a control tuning methodology for MMC‐STATCOM. For this purpose, the control and tuning strategies are presented. Since MMC‐STATCOM can employ different modulation strategies, two distinct modulation strategies are considered: nearest‐level control, with variable switching frequency; and phase‐shifted carrier pulse‐width modulation, with fixed switching frequency. Moreover, the proposal was validated through simulation and an experimental platform. The results indicate that the power response follows the reference, besides supplying the internal losses of the converter. The 10% ripple tolerance of the submodule voltages is respected in steady state for both modulation strategies. Moreover, the 5% total demand distortion (TDD) limit recommended by the Institute of Electrical and Electronics Engineers (IEEE) standard is attended. These results demonstrate the effectiveness of the controls employed.
A straightforward methodology for the control tuning of modular multilevel converter (MMC)‐static synchronous compensators (STATCOMs), which facilitates the testing and validation of techniques in these converters.
Experimental validation of the control tuning methodology in a laboratory MMC setup.
Evaluation of the proposal applied in different designs and voltage levels and distinct modulation strategies.
Mitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are protein‐ and lipid‐enriched hubs that mediate interorganellar communication by contributing to the dynamic transfer of Ca2+, ...lipid, and other metabolites between these organelles. Defective MERCs are associated with cellular oxidative stress, neurodegenerative disease, and cardiac and skeletal muscle pathology via mechanisms that are poorly understood. We previously demonstrated that skeletal muscle‐specific knockdown (KD) of the mitochondrial fusion mediator optic atrophy 1 (OPA1) induced ER stress and correlated with an induction of Mitofusin‐2, a known MERC protein. In the present study, we tested the hypothesis that Opa1 downregulation in skeletal muscle cells alters MERC formation by evaluating multiple myocyte systems, including from mice and Drosophila, and in primary myotubes. Our results revealed that OPA1 deficiency induced tighter and more frequent MERCs in concert with a greater abundance of MERC proteins involved in calcium exchange. Additionally, loss of OPA1 increased the expression of activating transcription factor 4 (ATF4), an integrated stress response (ISR) pathway effector. Reducing Atf4 expression prevented the OPA1‐loss‐induced tightening of MERC structures. OPA1 reduction was associated with decreased mitochondrial and sarcoplasmic reticulum, a specialized form of ER, calcium, which was reversed following ATF4 repression. These data suggest that mitochondrial stress, induced by OPA1 deficiency, regulates skeletal muscle MERC formation in an ATF4‐dependent manner.
Following Opa1‐deficiency in skeletal muscle, increases in ATF4 induce changes in mitochondria‐endoplasmic reticulum contact sites.
During pathological hypertrophy, peroxisome proliferator‐activated receptor coactivator 1α (PGC‐1α) is repressed in concert with reduced mitochondrial oxidative capacity and fatty acid oxidation ...(FAO). We therefore sought to determine if maintaining or increasing PGC‐1α levels in the context of pressure overload hypertrophy (POH) would preserve mitochondrial function and prevent contractile dysfunction. Pathological cardiac hypertrophy was induced using 4 wk of transverse aortic constriction (TAC) in mice overexpressing the human PGC‐1α genomic locus via a bacterial artificial chromosome (TG) and non‐transgenic controls (Cont). PGC‐1α levels were increased by 40% in TG mice and were sustained following TAC. Although TAC‐induced repression of FAO genes and oxidative phosphorylation (oxphos) genes was prevented in TG mice, mitochondrial function and ATP synthesis were equivalently impaired in Cont and TG mice after TAC. Contractile function was also equally impaired in Cont and TG mice following TAC, as demonstrated by decreased +dP/dt and ejection fraction and increased left ventricular developed pressure and end diastolic pressure. Conversely, capillary density was preserved, in concert with increased VEGF expression, while apoptosis and fibrosis were reduced in TG relative to Cont mice after TAC. Hence, sustaining physiological levels of PGC‐1α expression following POH, while preserving myocardial vascularity, does not prevent mitochondrial and contractile dysfunction.—Pereira, R. O., Wende, A. R., Crum, A., Hunter, D., Olsen, C. D., Rawlings, T., Riehle, C., Ward, W. F., Abel, E. D. Maintaining PGC‐1α expression following pressure overload‐induced cardiac hypertrophy preserves angiogenesis but not contractile or mitochondrial function. FASEB J. 28, 3691–3702 (2014). www.fasebj.org
Diabetes mellitus increases the risk for cardiac dysfunction, heart failure, and sudden death. The wide array of neurohumoral changes associated with diabetes pose a challenge to understanding the ...roles of specific pathways that alter cardiac function. Here, we use a mouse model with cardiomyocyte-restricted deletion of insulin receptors (CIRKO, cardiac-specific insulin receptor knockout) to study the specific effects of impaired cardiac insulin signaling on ventricular repolarization, independent of the generalized metabolic derangements associated with diabetes. Impaired insulin action caused a reduction in mRNA and protein expression of several key K(+) channels that dominate ventricular repolarization. Specifically, components of transient outward K(+) current fast component (Ito,fast; Kv4.2 and KChiP2) were reduced, consistent with a reduction in the amplitude of Ito,fast in isolated left ventricular CIRKO myocytes, compared with littermate controls. The reduction in Ito,fast resulted in ventricular action potential prolongation and prolongation of the QT interval on the surface ECG. These results support the notion that the lack of insulin signaling in the heart is sufficient to cause the repolarization abnormalities described in other animal models of diabetes.
Cover Image, Volume 239, Number 4, April 2024 Hinton, Antentor; Katti, Prasanna; Mungai, Margaret ...
Journal of cellular physiology,
April 2024, 2024-04-00, 20240401, Letnik:
239, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Inside Front Cover Caption: The cover image is based on the Research Article ATF4‐dependent increase in mitochondrial‐endoplasmic reticulum tethering following OPA1 deletion in skeletal muscle by ...Antentor Hinton Jr. et al., https://doi.org/10.1002/jcp.31204.
Obesity is associated with increased risk of several chronic diseases and the loss of disease-free years, which has increased the focus of much research for the discovery of therapy to combat it. ...Under healthy conditions, women tend to store more fat in subcutaneous deposits. However, this sexual dimorphism tends to be lost in the presence of comorbidities, such as type 2 diabetes mellitus (T2DM). Aerobic physical exercise (APE) has been applied in the management of obesity, however, is still necessary to better understand the effects of APE in obese female. Thus, we investigated the effect of APE on body weight, adiposity, exercise tolerance and glucose metabolism in female ob/ob mice. Eight-weeks-old female wild-type C57BL/6J and leptin-deficient ob/ob mice (Lep
) were distributed into three groups: wild-type sedentary group (Wt; n = 6), leptin-deficient sedentary group (Lep
S; n = 5) and leptin-deficient trained group (Lep
T; n = 8). The Lep
T mice were subjected to 8 weeks of aerobic physical exercise (APE) at 60% of the maximum velocity achieved in the running capacity test. The APE had no effect in attenuating body weight gain, and did not reduce subcutaneous and retroperitoneal white adipose tissue (SC-WAT and RP-WAT, respectively) and interscapular brown adipose tissue (iBAT) weights. The APE neither improved glucose intolerance nor insulin resistance in the Lep
T group. Also, the APE did not reduce the diameter or the area of RP-WAT adipocytes, but the APE reduced the diameter and the area of SC-WAT adipocytes, which was associated with lower fasting glycemia and islet/pancreas area ratio in the Lep
T group. In addition, the APE increased exercise tolerance and this response was also associated with lower fasting glycemia in the Lep
T group. In conclusion, starting APE at a later age with a more severe degree of obesity did not attenuate the excessive body weight gain, however the APE promoted benefits that can improve the female health, and for this reason it should be recommended as a non-pharmacological therapy for obesity.
Abstract Introduction Cysts and granulomas are chronic periapical lesions mediated by a set of inflammatory mediators that develop to contain a periapical infection. This study analyzed the nature of ...the inflammatory infiltrate, presence of mast cells, and in situ expression of cytokines (interleukin IL-17 and transforming growth factor TGF-ß), chemokines (macrophage inflammatory protein MIP-1ß and monocyte chemotactic protein MCP-1), and nuclear transcription factor (FoxP3) in human periapical granulomas and cysts compared with a control group. Methods Fifty-five lesions (25 periapical cysts, 25 periapical granulomas, and 5 controls) were analyzed. The type of inflammatory infiltrate was evaluated by hematoxylin-eosin staining, and the presence of mast cells was analyzed by toluidine blue staining. Indirect immunohistochemistry was used to evaluate the expression of cytokines, chemokines, and FoxP3. Results The inflammatory infiltrate mainly consisted of mononuclear cells. In cysts, mononuclear infiltrates were significantly more frequent than mixed (polymorphonuclear/mononuclear) infiltrates ( P = .04). Mixed inflammatory infiltrates were significantly more frequent in patients with sinus tract ( P = .0001). The number of mast cells was significantly higher in granulomas than in cystic lesions ( P = .02). A significant difference in the expression of IL-17 ( P = .001) and TGF-ß ( P = .003) was observed between cysts and granulomas and the control group. Significantly higher IL-17 levels were also observed in cases of patients with sinus tract ( P = .03). Conclusions We observed that chronic periapical lesions might experience a reagudization process that is correlated with an increased leukocyte infiltration, with the predominance of neutrophils attracted by a chemokine milieu, as well as the increased presence of IL-17.
In obesity, skeletal muscle mitochondrial activity changes to cope with increased nutrient availability. Autophagy has been proposed as an essential mechanism involved in the regulation of ...mitochondrial metabolism. Still, the contribution of autophagy to mitochondrial adaptations in skeletal muscle during obesity is unknown. Here, we show that in response to high‐fat diet (HFD) feeding, distinct skeletal muscles in mice exhibit differentially regulated autophagy that may modulate mitochondrial activity. We observed that after 4 and 40 weeks of high‐fat diet feeding, OXPHOS subunits and mitochondrial DNA content increased in the oxidative soleus muscle. However, in gastrocnemius muscle, which has a mixed fiber‐type composition, the mitochondrial mass increased only after 40 weeks of HFD feeding. Interestingly, fatty acid‐supported mitochondrial respiration was enhanced in gastrocnemius, but not in soleus muscle after a 4‐week HFD feeding. This increased metabolic profile in gastrocnemius was paralleled by preserving autophagy flux, while autophagy flux in soleus was reduced. To determine the role of autophagy in this differential response, we used an autophagy‐deficient mouse model with partial deletion of Atg7 specifically in skeletal muscle (SkM‐Atg7+/− mice). We observed that Atg7 reduction resulted in diminished autophagic flux in skeletal muscle, alongside blunting the HFD‐induced increase in fatty acid‐supported mitochondrial respiration observed in gastrocnemius. Remarkably, SkM‐Atg7+/− mice did not present increased mitochondria accumulation. Altogether, our results show that HFD triggers specific mitochondrial adaptations in skeletal muscles with different fiber type compositions, and that Atg7‐mediated autophagy modulates mitochondrial respiratory capacity but not its content in response to an obesogenic diet.
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