Full-color, three-dimensional images of objects under incoherent illumination are obtained by a digital holography technique. Based on self-interference of two beam-split copies of the object's ...optical field with differential curvatures, the apparatus consists of a beam-splitter, a few mirrors and lenses, a piezo-actuator, and a color camera. No lasers or other special illuminations are used for recording or reconstruction. Color holographic images of daylight-illuminated outdoor scenes and a halogen lamp-illuminated toy figure are obtained. From a recorded hologram, images can be calculated, or numerically focused, at any distances for viewing.
Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, ...but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca2+ levels and activates the CamKKβ-AMPK pathway via phospholipase C and the ryanodine receptor Ca2+-release channel. As a consequence, resveratrol increases NAD+ and the activity of Sirt1. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. Therefore, administration of PDE4 inhibitors may also protect against and ameliorate the symptoms of metabolic diseases associated with aging.
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► Resveratrol competitively inhibits cAMP-degrading PDEs and activates Epac1 ► Epac1 activates the CamKKβ-AMPK pathway via PLC and Ryr Ca2+ channel ► Resveratrol activates Sirt1 indirectly via the Epac1-CamKKβ-AMPK pathway ► PDE4 inhibitors rolipram and resveratrol have equivalent metabolic effects in mice
The antiaging, antidiabetic polyphenol in red wine indirectly activates Sirt1 via competitive inhibition of cAMP-phosphodiesterases to ultimately increase NAD+ levels. This suggests that PDEs are potential therapeutic targets for aging-related metabolic disorders.
Digital Holography and Microscopy presents an introduction to the field, and reviews the research and development activities in digital holography. Topics include the general theory of diffraction ...and holography formations, and practical instrumentation and experimentation of digital holography.
We propose a single-shot incoherent holographic imaging technique that adopts self-interference incoherent digital holography (SIDH) with slight tilt of the plane mirror in the optical configuration. ...The limited temporal coherence length of the illumination leads the guide-star hologram of the proposed system to have a Gaussian envelope of elliptical ring shape. The observation shows that the reconstruction by cross correlation with the guide-star hologram achieves better quality than the usual propagation methods. Experimentally, we verify that the hologram and 3D reconstruction can be implemented incoherently with the proposed single-shot off-axis SIDH.
Mitochondrial stress releases mitochondrial DNA (mtDNA) into the cytosol, thereby triggering the type Ι interferon (IFN) response. Mitochondrial outer membrane permeabilization, which is required for ...mtDNA release, has been extensively studied in apoptotic cells, but little is known about its role in live cells. We found that oxidatively stressed mitochondria release short mtDNA fragments via pores formed by the voltage-dependent anion channel (VDAC) oligomers in the mitochondrial outer membrane. Furthermore, the positively charged residues in the N-terminal domain of VDAC1 interact with mtDNA, promoting VDAC1 oligomerization. The VDAC oligomerization inhibitor VBIT-4 decreases mtDNA release, IFN signaling, neutrophil extracellular traps, and disease severity in a mouse model of systemic lupus erythematosus. Thus, inhibiting VDAC oligomerization is a potential therapeutic approach for diseases associated with mtDNA release.
Background: This meta-analysis aimed to investigate the effect of antioxidant supplements on the primary and secondary prevention of cancer as reported by randomized controlled trials. Methods: We ...searched Medline (PubMed), Excerpta Medica database, and the Cochrane Review in October 2007. Results: Among 3327 articles searched, 31 articles on 22 randomized controlled trials, which included 161 045 total subjects, 88 610 in antioxidant supplement groups and 72 435 in placebo or no-intervention groups, were included in the final analyses. In a fixed-effects meta-analysis of all 22 trials, antioxidant supplements were found to have no preventive effect on cancer relative risk (RR) 0.99; 95% confidence interval (CI) 0.96–1.03). Similar findings were observed in 12 studies on primary prevention trials (RR 1.00; 95% CI 0.97–1.04) and in nine studies on secondary prevention trials (RR 0.97; 95% CI 0.83–1.13). Further, subgroup analyses revealed no preventive effect on cancer according to type of antioxidant, type of cancer, or the methodological quality of the studies. On the other hand, the use of antioxidant supplements significantly increased the risk of bladder cancer (RR 1.52; 95% CI 1.06–2.17) in a subgroup meta-analysis of four trials. Conclusions: The meta-analysis of randomized controlled trials indicated that there is no clinical evidence to support an overall primary and secondary preventive effect of antioxidant supplements on cancer. The effects of antioxidant supplements on human health, particularly in relation to cancer, should not be overemphasized because the use of those might be harmful for some cancer.
Resveratrol, a natural polyphenolic compound that is found in grapes and red wine, increases metabolic rate, insulin sensitivity, mitochondrial biogenesis, and physical endurance and reduces fat ...accumulation in mice. Although it is thought that resveratrol targets Sirt1, this is controversial because resveratrol also activates 5' AMP-activated protein kinase (AMPK), which also regulates insulin sensitivity and mitochondrial biogenesis. Here, we use mice deficient in AMPKalpha1 or -alpha2 to determine whether the metabolic effects of resveratrol are mediated by AMPK.
Mice deficient in the catalytic subunit of AMPK (alpha1 or alpha2) and wild-type mice were fed a high-fat diet or high-fat diet supplemented with resveratrol for 13 weeks. Body weight was recorded biweekly and metabolic parameters were measured. We also used mouse embryonic fibroblasts deficient in AMPK to study the role of AMPK in resveratrol-mediated effects in vitro.
Resveratrol increased the metabolic rate and reduced fat mass in wild-type mice but not in AMPKalpha1(-/-) mice. In the absence of either AMPKalpha1 or -alpha2, resveratrol failed to increase insulin sensitivity, glucose tolerance, mitochondrial biogenesis, and physical endurance. Consistent with this, the expression of genes important for mitochondrial biogenesis was not induced by resveratrol in AMPK-deficient mice. In addition, resveratrol increased the NAD-to-NADH ratio in an AMPK-dependent manner, which may explain how resveratrol may activate Sirt1 indirectly.
We conclude that AMPK, which was thought to be an off-target hit of resveratrol, is the central target for the metabolic effects of resveratrol.
The functional interpretation of genome-wide association studies (GWAS) is challenging due to the cell-type-dependent influences of genetic variants. Here, we generated comprehensive maps of ...expression quantitative trait loci (eQTLs) for 659 microdissected human kidney samples and identified cell-type-eQTLs by mapping interactions between cell type abundances and genotypes. By partitioning heritability using stratified linkage disequilibrium score regression to integrate GWAS with single-cell RNA sequencing and single-nucleus assay for transposase-accessible chromatin with high-throughput sequencing data, we prioritized proximal tubules for kidney function and endothelial cells and distal tubule segments for blood pressure pathogenesis. Bayesian colocalization analysis nominated more than 200 genes for kidney function and hypertension. Our study clarifies the mechanism of commonly used antihypertensive and renal-protective drugs and identifies drug repurposing opportunities for kidney disease.
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