OBJECTIVE-We hypothesized that the induction of heme oxygenase (HO)-1 and increased HO activity, which induces arterial antioxidative enzymes and vasoprotection in a mouse and a rat model of diabetes, would ameliorate insulin resistance, obesity, and diabetes in the ob mouse model of type 2 diabetes.RESEARCH DESIGN AND METHODS-Lean and ob mice were intraperitoneally administered the HO-1 inducer cobalt protoporphyrin (3 mg/kg CoPP) with and without the HO inhibitor stannous mesoporphyrin (2 mg/100 g SnMP) once a week for 6 weeks. Body weight, blood glucose, and serum cytokines and adiponectin were measured. Aorta, adipose tissue, bone marrow, and mesenchymal stem cells (MSCs) were isolated and assessed for HO expression and adipogenesis.RESULTS-HO activity was reduced in ob mice compared with age-matched lean mice. Administration of CoPP caused a sustained increase in HO-1 protein, prevented weight gain, decreased visceral and subcutaneous fat content (P Ͻ 0.03 and 0.01, respectively, compared with vehicle animals), increased serum adiponectin, and decreased plasma tumor necrosis factor-␣ (TNF-␣), interleukin (IL)-6, and IL-1 levels (P Ͻ 0.05). HO-1 induction improved insulin sensitivity and glucose tolerance and decreased insulin levels. Upregulation of HO-1 decreased adipogenesis in bone marrow in vivo and in cultured MSCs and increased adiponectin levels in the culture media. Inhibition of HO activity decreased adiponectin and increased secretion of TNF-␣, IL-6, and IL-1 levels in ob mice.CONCLUSIONS-This study provides strong evidence for the existence of an HO-1-adiponectin regulatory axis that can be manipulated to ameliorate the deleterious effects of obesity and the metabolic syndrome associated with cardiovascular disease and diabetes. Diabetes 57:1526-1535, 2008
The SIRT1 deacetylase inhibits fat synthesis and stimulates fat oxidation in response to fasting, but the underlying mechanisms remain unclear. Here we report that SREBP-1c, a key lipogenic activator, is an in vivo target of SIRT1. SIRT1 interaction with SREBP-1c was increased during fasting and decreased upon feeding, and consistently, SREBP-1c acetylation levels were decreased during fasting in mouse liver. Acetylated SREBP-1c levels were also increased in HepG2 cells treated with insulin and glucose to mimic feeding conditions, and down-regulation of p300 by siRNA decreased the acetylation. Depletion of hepatic SIRT1 by adenoviral siRNA increased acetylation of SREBP-1c with increased lipogenic gene expression. Tandem mass spectrometry and mutagenesis studies revealed that SREBP-1c is acetylated by p300 at Lys-289 and Lys-309. Mechanistic studies using acetylation-defective mutants showed that SIRT1 deacetylates and inhibits SREBP-1c transactivation by decreasing its stability and its occupancy at the lipogenic genes. Remarkably, SREBP-1c acetylation levels were elevated in dietinduced obese mice, and hepatic overexpression of SIRT1 or treatment with resveratrol, a SIRT1 activator, daily for 1 week decreased acetylated SREBP-1c levels with beneficial functional outcomes. These results demonstrate an intriguing connection between elevated SREBP-1c acetylation and increased lipogenic gene expression, suggesting that abnormally elevated SREBP-1c acetylation increases SREBP-1c lipogenic activity in obese mice. Reducing acetylation of SREBP-1c by targeting SIRT1 may be useful for treating metabolic disorders, including fatty liver, obesity, and type II diabetes.The NAD ϩ -dependent SIRT1 (sirtuin 1) deacetylase plays a critical role in cellular metabolism, stress responses, and possibly aging by modulating the activity of transcription factors and cofactors by protein deacetylation (1-4). In response to low nutritional availability, SIRT1 functions as a master switch to maintain lipid and glucose homeostasis and energy balance by regulating important metabolic regulators, such as PGC-1␣ (PPAR␥ coactivator ␣), Foxo-1, and liver X receptor (1, 5-7). We recently identified the nuclear bile acid receptor, farnesoid X receptor (FXR), 3 as an important in vivo target of SIRT1 in the regulation of hepatic lipid metabolism (8). Of these reported regulators, the function of SIRT1 in deacetylating and enhancing the activity of PGC-1␣ has been well established (1,5,9,10).
Neural stem cell (NSC) transplantation has been investigated as a means to reconstitute the damaged brain after stroke. In this study, however, we investigated the effect on acute cerebral and peripheral inflammation after intracerebral haemorrhage (ICH). NSCs (H1 clone) from fetal human brain were injected intravenously (NSCs-iv, 5 million cells) or intracerebrally (NSCs-ic, 1 million cells) at 2 or 24 h after collagenase-induced ICH in a rat model. Only NSCs-iv-2 h resulted in fewer initial neurologic deteriorations and reduced brain oedema formation, inflammatory infiltrations (OX-42, myeloperoxidase) and apoptosis (activated caspase-3, TUNEL) compared to the vehicle-injected control animals. Rat neurosphere-iv-2 h, but not human fibroblast-iv-2 h, also reduced the brain oedema and the initial neurologic deficits. Human NSCs-iv-2 h also attenuated both cerebral and splenic activations of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-kappaB). However, we observed only a few stem cells in brain sections of the NSCs-iv-2 h group; in the main, they were detected in marginal zone of spleens. To investigate whether NSCs interact with spleen to reduce cerebral inflammation, we performed a splenectomy prior to ICH induction, which eliminated the effect of NSCs-iv-2 h transplantation on brain water content and inflammatory infiltrations. NSCs also inhibited in vitro macrophage activations after lipopolysaccharide stimulation in a cell-to-cell contact dependent manner. In summary, early intravenous NSC injection displayed anti-inflammatory functionality that promoted neuroprotection, mainly by interrupting splenic inflammatory responses after ICH.
We use transmission electron microscopy (TEM) to investigate the evolution of the surface structure of Li x Ni0.8Co0.15Al0.05O2 cathode materials (NCA) as a function of the extent of first charge at room temperature using a combination of high-resolution electron microscopy (HREM) imaging, selected area electron diffraction (SAED), and electron energy loss spectroscopy (EELS). It was found that the surface changes from the layered structure (space group R3̅m) to the disordered spinel structure (Fd3̅m), and eventually to the rock-salt structure (Fm3̅m), and that these changes are more substantial as the extent of charge increases. EELS indicates that these crystal structure changes are also accompanied by significant changes in the electronic structure, which are consistent with delithiation leading to both a reduction of the Ni and an increase in the effective electron density of oxygen. This leads to a charge imbalance, which results in the formation of oxygen vacancies and the development of surface porosity. The degree of local surface structure change differs among particles, likely due to kinetic factors that are manifested with changes in particle size. These results demonstrate that TEM, when coupled with EELS, can provide detailed information about the crystallographic and electronic structure changes that occur at the surface of these materials during delithiation. This information is of critical importance for obtaining a complete understanding of the mechanisms by which both degradation and thermal runaway initiate in these electrode materials.
Continuous monitoring of an arterial pulse using a pressure sensor attached on the epidermis is an important technology for detecting the early onset of cardiovascular disease and assessing personal health status. Conventional pulse sensors have the capability of detecting human biosignals, but have significant drawbacks of power consumption issues that limit sustainable operation of wearable medical devices. Here, a self-powered piezoelectric pulse sensor is demonstrated to enable in vivo measurement of radial/carotid pulse signals in near-surface arteries. The inorganic piezoelectric sensor on an ultrathin plastic achieves conformal contact with the complex texture of the rugged skin, which allows to respond to the tiny pulse changes arising on the surface of epidermis. Experimental studies provide characteristics of the sensor with a sensitivity (≈0.018 kPa ), response time (≈60 ms), and good mechanical stability. Wireless transmission of detected arterial pressure signals to a smart phone demonstrates the possibility of self-powered and real-time pulse monitoring system.
The genome of soybean ( Glycine max ), a commercially important crop, has recently been sequenced and is one of six crop species to have been sequenced. Here we report the genome sequence of G. soja , the undomesticated ancestor of G. max (in particular, G. soja var. IT182932). The 48.8-Gb Illumina Genome Analyzer (Illumina-GA) short DNA reads were aligned to the G. max reference genome and a consensus was determined for G. soja . This consensus sequence spanned 915.4 Mb, representing a coverage of 97.65% of the G. max published genome sequence and an average mapping depth of 43-fold. The nucleotide sequence of the G. soja genome, which contains 2.5 Mb of substituted bases and 406 kb of small insertions/deletions relative to G. max , is ∼0.31% different from that of G. max . In addition to the mapped 915.4-Mb consensus sequence, 32.4 Mb of large deletions and 8.3 Mb of novel sequence contigs in the G. soja genome were also detected. Nucleotide variants of G. soja versus G. max confirmed by Roche Genome Sequencer FLX sequencing showed a 99.99% concordance in single-nucleotide polymorphism and a 98.82% agreement in insertion/deletion calls on Illumina-GA reads. Data presented in this study suggest that the G. soja / G. max complex may be at least 0.27 million y old, appearing before the relatively recent event of domestication (6,000∼9,000 y ago). This suggests that soybean domestication is complicated and that more in-depth study of population genetics is needed. In any case, genome comparison of domesticated and undomesticated forms of soybean can facilitate its improvement.
A fat-saturated twice-refocused spin echo sequence was implemented on a GE Signa 1.5-T whole-body system for diffusion-weighted imaging. Data were acquired using an analytically designed interleaved variable-density (VD) spiral readout trajectory. This flexible design algorithm allowed real-time prescription on the scanner. Each interleaf of the VD spiral oversampled the center of k-space. The oversampling provided an inherent motion compensation capability. The resultant diffusion-weighted images showed good quality without any retrospective motion correction. An iterated motion correction algorithm was developed to further reduce the signal cancellation artifact caused by motion-induced phase error. In this algorithm, a low-resolution phase map was estimated using the oversampled data in the center of k-space in order to correct for phase error in image space.In vivo diffusion tensor imaging (DTI) studies were performed on the brains of healthy volunteers. High-quality isotropic diffusion-weighted images, trace maps, and FA maps from axial, sagittal, and coronal slices were obtained using a VD spiral readout trajectory with matrix size 256 ؋ 256. To our knowl- Key words: magnetic resonance imaging; high resolution; diffusion; diffusion tensor imaging; variable density spiral; interleaved; motion correction Diffusion-weighted imaging (DWI) is a unique technique for studying random molecular motion in biologic tissues. Over the past decade, DWI has found routine applications in medical diagnosis, especially in detecting acute cerebral ischemia (1). Most diffusion-weighted images are currently acquired using a single-shot echo-planar imaging (EPI) technique. Single-shot EPI has the advantage of rapid image acquisition and insensitivity to phase error caused by subject motion because the entire k-space is acquired with a single rapid train of gradient echoes. Despite the rapid image formation, single-shot EPI lasts long enough that T 2 *-decay limits image resolution and off-resonant spins can still cause serious image degradation.To shorten the readout time, multishot sequences can be used (2,3); however, they generally suffer from view-toview phase variations caused by motion during the period when the diffusion-sensitizing gradients are turned on. One approach to correct these variations is to acquire additional navigator data that can be used to resolve the phase error (4 -7). The navigator can be implemented to correct for either one-dimensional or two-dimensional phase error. The navigator data are intended to provide a direct measure of the motion-induced phase variations. Under the assumption of rigid body motion, the data can be subsequently corrected for small amounts of motion.A few studies have recently explored the self-navigating capability of the spiral readout trajectory in multishot DWI (8,9). Magnetic resonance imaging (MRI) based on spiral readout has been found to be effective in various applications, including functional neuroimaging (10) and spectroscopy (11). The spiral trajectory has the me...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.