Objective
Restricting dietary methionine to 0.17% in male mice increases energy expenditure, reduces fat deposition, and improves metabolic health. The goal of this work was to compare each of these ...responses in postweaning male and female mice and in physically mature male and female mice.
Methods
Methionine‐restricted (MR) diets were fed to age‐matched cohorts of male and female mice for 8 to 10 weeks beginning at 8 weeks of age or beginning at 4 months of age. The physiological and transcriptional responses to MR were compared in the respective cohorts.
Results
Dietary MR produced sexually dimorphic changes in body composition in young growing animals, with males preserving lean at the expense of fat and females preserving fat at the expense of lean. The effects of MR on energy balance were comparable between sexes when the diet was initiated after attainment of physical maturity (4 months), and metabolic and endocrine responses were also comparable between males and females after 8 weeks on the MR diet.
Conclusions
The sexually dimorphic effects of MR are limited to nutrient partitioning between lean and fat tissue deposition in young, growing mice. Introduction of the diet after physical maturity produced comparable effects on growth and metabolic responses in male and female mice.
Abstract We compared changes in academic achievement across 3 years between children in elementary schools receiving the Academic Achievement and Physical Activity Across the Curriculum intervention ...(A + PAAC), in which classroom teachers were trained to deliver academic lessons using moderate-to-vigorous physical activity (MVPA) compared to a non-intervention control. Elementary schools in eastern Kansas ( n = 17) were cluster randomized to A + PAAC ( N = 9, target ≥ 100 min/w
ee
k
) or control ( N = 8). Academic achievement (math, reading, spelling) was assessed using the Wechsler Individual Achievement Test-Third Edition (WIAT-III) in a sample of children (A + PAAC = 316, Control = 268) in grades 2 and 3 at baseline (Fall 2011) and repeated each spring across 3 years. On average 55 min/w
ee
k
of A + PACC lessons were delivered each week across the intervention. Baseline WIAT-III scores (math, reading, spelling) were significantly higher in students in A + PAAC compared with control schools and improved in both groups across 3 years. However, linear mixed modeling, accounting for baseline between group differences in WIAT-III scores, ethnicity, family income, and cardiovascular fitness, found no significant impact of A + PAAC on any of the academic achievement outcomes as determined by non-significant group by time interactions. A + PAAC neither diminished or improved academic achievement across 3-years in elementary school children compared with controls. Our target of 100 min
/w
ee
k
of active lessons was not achieved; however, students attending A + PAAC schools received an additional 55 min
/w
ee
k
of MVPA which may be associated with both physical and mental health benefits, without a reduction in time devoted to academic instruction.
Next generation wound care technology capable of diagnosing wound parameters, promoting healthy cell growth, and reducing pathogenic infections noninvasively would provide patients with an improved ...standard of care and accelerated wound repair. Temperature is one of the indicating biomarkers specific to chronic wounds. This work reports a hybrid, multifunctional optical material platformnanodiamond (ND)–silk membranes as biopolymer dressings capable of temperature sensing and promoting wound healing. The hybrid structure was fabricated through electrospinning, and 3D submicron fibrous membranes with high porosity were formed. Silk fibers are capable of compensating for the lack of an extracellular matrix at the wound site, supporting the wound-healing process. Negatively charged nitrogen vacancy (NV–) color centers in NDs exhibit optically detected magnetic resonance (ODMR) and act as nanoscale thermometers. This can be exploited to sense temperature variations associated with the presence of infection or inflammation in a wound, without physically removing the dressing. Our results show that the presence of NDs in the hybrid ND–silk membranes improves the thermal stability of silk fibers. NV– color centers in NDs embedded in silk fibers exhibit well-retained fluorescence and ODMR. Using the NV– centers as fluorescent nanoscale thermometers, we achieved temperature sensing in 25–50 °C, including the biologically relevant temperature window, for cell-grown ND–silk membranes. An enhancement (∼1.5× on average) in the temperature sensitivity of the NV– centers was observed for the hybrid materials. The hybrid membranes were further tested in vivo in a murine wound-healing model and demonstrated biocompatibility and equivalent wound closure rates as the control wounds. Additionally, the hybrid ND–silk membranes exhibited selective antifouling and biocidal propensity toward Gram-negative Pseudomonas aeruginosa and Escherichia coli, while no effect was observed on Gram-positive Staphylococcus aureus.
Objective: Direct oral anticoagulants (DOACs) are recommended for the prevention of stroke or systemic embolism in nonvalvular atrial fibrillation. Dabigatran, rivaroxaban, apixaban, and edoxaban ...represent possible alternatives to warfarin in the setting of cardioversion. A literature review was conducted to evaluate the safety and efficacy of DOAC use pericardioversion. Data Sources: A PubMed and MEDLINE search through August 2017 was conducted using the following search terms alone or in various combinations: dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban, DOAC, NOAC, TSOAC, cardioversion. Study Selection and Data Extraction: All English-language, human studies comparing the safety and efficacy of DOACs with that of other anticoagulants in the setting of cardioversion were eligible for inclusion. References from published articles were reviewed for additional relevant citations for study inclusion. Four retrospective and 2 prospective trials comparing DOACs with warfarin were identified. Data Synthesis: The majority of studies included patients undergoing electric cardioversion. Based on current evidence, the DOACs perform similarly to warfarin in the prevention of stroke and systemic embolism, and bleeding rates are comparable. Conclusions: DOACs may be an attractive alternative to warfarin because of fast onset of action, potentially reducing delay to cardioversion. More robust studies are needed in patients with renal dysfunction and patients undergoing pharmacological cardioversion.
Multimodal imaging promises to revolutionize the understanding of biological processes across scales in space and time by combining the strengths of multiple imaging techniques. Fluorescent ...nanodiamonds (FNDs) are biocompatible, chemically inert, provide high contrast in light‐ and electron‐based microscopy, and are versatile optical quantum sensors. Here it is demonstrated that FNDs also provide high absorption contrast in nanoscale 3D soft X‐ray tomograms with a resolution of 28 nm in all dimensions. Confocal fluorescence, atomic force, and scanning electron microscopy images of FNDs inside and on the surface of PC3 cancer cells with sub‐micrometer precision are correlated. FNDs are found inside ≈1 µm sized vesicles present in the cytoplasm, providing direct evidence of the active uptake of bare FNDs by cancer cells. Imaging artefacts are quantified and separated from changes in cell morphology caused by sample preparation. These results demonstrate the utility of FNDs in multimodal imaging, contribute to the understanding of the fate of FNDs in cells, and open up new possibilities for biological imaging and sensing across the nano‐ and microscale.
Understanding biochemical and physical processes inside cells in detail remains a scientific frontier. Multimodal imaging enables imaging and sensing across many scales in time and space. Fluorescent nanodiamonds (FNDs) are stable and biocompatible nanoscale sensors for temperature and magnetic fields. This study shows that FNDs are excellent tools for multimodal imaging that provide outstanding imaging contrast in many imaging modalities.
Objective
Restricting dietary methionine to 0.17% in mice increases energy expenditure (EE), reduces fat deposition, and improves metabolic health by increasing hepatic fibroblast growth factor 21 ...(FGF21). The goal of this study was to compare each of these responses in mice with the coreceptor for FGF21 deleted in either adipose tissue or the brain.
Methods
Methionine‐restriction (MR) diets were fed to age‐matched cohorts of mice with the coreceptor for FGF21 deleted in either adipose tissue or the brain. The physiological and transcriptional responses to MR were compared in the respective cohorts.
Results
Tissue‐specific deletion of the FGF21 coreceptor in adipose tissue did not abrogate the ability of dietary MR to increase EE and reduce fat deposition. Tissue‐specific deletion of the FGF21 coreceptor from the brain produced mice that were unable to respond to the effects of MR on EE or the remodeling of adipose tissue.
Conclusions
The increase in FGF21 produced by dietary MR acts primarily in the brain to produce its physiological effects on energy balance. In contrast, the effects of MR on hepatic gene expression were intact in both models, supporting a mechanism that directly links detection of reduced methionine in the liver to transcriptional mechanisms that alter gene expression in the liver.
One of the mechanisms by which cancer cells acquire hyperinvasive and migratory properties with progressive loss of epithelial markers is the epithelial-to-mesenchymal transition (EMT). We have ...previously reported that in different cancer types, including nonsmall cell lung cancer (NSCLC), the microRNA-183/96/182 cluster (m96cl) is highly repressed in cells that have undergone EMT. In the present study, we used a novel conditional m96cl mouse to establish that loss of m96cl accelerated the growth of Kras mutant autochthonous lung adenocarcinomas. In contrast, ectopic expression of the m96cl in NSCLC cells results in a robust suppression of migration and invasion in vitro, and tumor growth and metastasis in vivo. Detailed immune profiling of the tumors revealed a significant enrichment of activated CD8
cytotoxic T lymphocytes (CD8
CTLs) in m96cl-expressing tumors, and m96cl-mediated suppression of tumor growth and metastasis was CD8
CTL-dependent. Using coculture assays with naïve immune cells, we show that m96cl expression drives paracrine stimulation of CD8
CTL proliferation and function. Using tumor microenvironment-associated gene expression profiling, we identified that m96cl elevates the interleukin-2 (IL2) signaling pathway and results in increased IL2-mediated paracrine stimulation of CD8
CTLs. Furthermore, we identified that the m96cl modulates the expression of IL2 in cancer cells by regulating the expression of transcriptional repressors Foxf2 and Zeb1, and thereby alters the levels of secreted IL2 in the tumor microenvironment. Last, we show that in vivo depletion of IL2 abrogates m96cl-mediated activation of CD8
CTLs and results in loss of metastatic suppression. Therefore, we have identified a novel mechanistic role of the m96cl in the suppression of lung cancer growth and metastasis by inducing an IL2-mediated systemic CD8
CTL immune response.
Fluorescent nanodiamonds (FNDs) containing quantum defects enable the optical measurement of electromagnetic fields and temperature and are among the most developed nanoscale quantum sensors today. ...Yet, for many applications in biomedicine and beyond, FNDs must be integrated into biocompatible substrates that preserve FND sensitivity and bring FNDs within nanoscale distance of their sensing target. At the same time, the high excitation light intensity required for most quantum sensing protocols remains a major challenge for applications in biomedicine. Here, it is shown that FNDs embedded in polyvinyl‐alcohol (PVA) fibers are a powerful 3D platform for nanoscale quantum sensing via light guiding. First, it is demonstrated that biocompatible PVA fibers can guide light to excite FNDs >10 µm from the excitation beam. Using this light‐guiding‐enabled excitation, optically detected magnetic resonance (ODMR) and T1 spin relaxometry measurements are performed using the nitrogen‐vacancy (NV) center in FNDs. Through ODMR thermometry, it is shown that light‐guiding‐enabled excitation mitigates light‐induced heating. Finally, the quantum sensing capability of the platform is established by detecting paramagnetic gadolinium in a dry and aqueous environment using T1 relaxometry of the NV center in FNDs. These results pave the way for light‐guiding‐enabled optical quantum sensing in biomedicine using nanodiamond‐doped biosubstrates.
Electrospun PVA fibers can guide light to excite fluorescent nanodiamonds embedded in the fibers. Using this light‐guiding‐enabled excitation, optically detected magnetic resonance (ODMR) and T1 spin relaxometry measurements using the nitrogen‐vacancy center in fluorescent nanodiamonds are demonstrated. ODMR thermometry shows that light‐guiding‐enabled excitation mitigates light‐induced heating. Quantum sensing is demonstrated by detecting gadolinium in dry and aqueous environments.
Zinc oxide (ZnO) is a promising semiconductor that is suitable for bioimaging applications due to its intrinsic defect fluorescence. However, ZnO generally suffers from poor photostability. We report ...room-temperature single-photon emission from optical defects found in ZnO nanoparticles (NPs) formed by ion implantation followed by thermal oxidation in a silica substrate. We conduct a thorough investigation into the photophysics of a particularly bright defect and identify other single emitters within the NPs. Photostability was observed when the NPs were removed from the growth substrate and taken up by skin cells for
imaging.
Abstract Obesity rates are associated with public health consequences and rising health care costs. Weight loss interventions, while effective, do not work for everyone, and weight regain is a ...significant problem. Eating behavior is influenced by a convergence of processes in the brain, including homeostatic factors and motivational processing that are important contributors to overeating. Initial neuroimaging studies have identified brain regions that respond differently to visual food cues in obese and healthy weight individuals that are positively correlated with reports of hunger in obese participants. While these findings provide mechanisms of overeating, many important questions remain. It is not known whether brain activation patterns change after weight loss, or if they change differentially based on amount of weight lost. Also, little is understood regarding biological processes that contribute to long-term weight maintenance. This study will use neuroimaging in participants while viewing food and non-food images. Functional Magnetic Resonance Imaging will take place before and after completion of a twelve-week weight loss intervention. Obese participants will be followed though a 6-month maintenance period. The study will address three aims: 1. Characterize brain activation underlying food motivation and impulsive behaviors in obese individuals. 2. Identify brain activation changes and predictors of weight loss. 3. Identify brain activation predictors of weight loss maintenance. Findings from this study will have implications for understanding mechanisms of obesity, weight loss, and weight maintenance. Results will be significant to public health and could lead to a better understanding of how differences in brain activation relate to obesity.
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