Fermentable Non-Digestible Dietary Fiber and Bioactive Compounds Affect Aging and Fat Deposition in Caenorhabditis elegans

Overweight and obesity have been imposing $147 billion a year to the health care system in the United States. Limited medications are available in the market with side effects. Surgical treatments are second-line obesity treatments. Short chain fatty acids (SCFAs) produced from the fermentable resistant starch improves the secretion of satiety hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) from L-endocrine cells of cecum and colon. We hypothesized that consumption of fermentable non-digestible dietary fiber and bioactive compounds will increase insulin sensitivity, reduce body fat, and improve healthspan in Caenorhabditis elegans (C. elegans), and hyperglycemia (2% glucose) that may cause insulin resistance and impair lipid metabolism will attenuate these effects. Wild type C. elegans N2 or sir-2.1(ok434)IV, daf-16(mgDf50)I, and daf-16(mgDf50)I;daf-2(m65)III mutants were used. The control animals were fed with E. coli OP50. Experimental groups were fed with additional treatments: butyrate (0.3mM, 0.6mM), sodium acetate (5mM, 50mM), sodium propionate (7mM), or tributyrin (0.5mM, 3mM); PWB, oats or wheat bran (0.5%, 1.0%, or 3.0% w/v) with or without additional 2% glucose. SCFAs increased the lifespan of N2 and daf-16(mgDf50)I, but reduced lifespan in the daf-16/daf-2 deficient and sir-2.1(ok434)IV mutants. PWB or wheat bran sustained the pharyngeal pumping rate (PPR) in N2, sir-2.1(ok434)IV, daf-16(mgDf50)I, and daf-16(mgDf50)I;daf-2(m65)III. The N2, daf-16, or sir-2.1 mutant increased the PPR following oat consumption. This increase persisted in the presence of glucose at a low dose in daf-16 or daf-16/daf-2 mutant. The Nile red stained intestinal fat deposition (IFD) was reduced by butyrate (0.3, 0.6mM), acetate (100mM), propionate (0.3mM), and tributyrin (0.1, 1mM) in N2; and was increased in sir-2.1 mutant. PWB reduced IFD in N2, sir-2.1 or daf-16 mutants. Hyperglycaemia attenuated the effects on IFD in N2 or daf-16/daf-2 mutant. Oat-feeding decreased IFD in N2, and daf-16 or daf-16/daf-2 mutant with or without hyperglycaemia. Wheat bran reduced IFD in N2, and in daf-16 or daf-16/daf-2 mutants without hyperglycemia, while hyperglycemia increased IFD in sir-2.1(ok434)IV. In summary, PWB, oats, wheat bran, and SCFAs reduced the IFD and improved the healthspan in C. elegans, and these effects were mediated by the sir-2.1, daf-2, or daf-2/daf-16 pathways

Power-Aware Planning and Design for Next Generation Wireless Networks

Mobile network operators have witnessed a transition from being voice dominated to video/data domination, which leads to a dramatic traffic growth over the past decade. With the 4G wireless communication systems being deployed in the world most recently, the fifth generation (5G) mobile and wireless communica- tion technologies are emerging into research fields. The fast growing data traffic volume and dramatic expansion of network infrastructures will inevitably trigger tremendous escalation of energy consumption in wireless networks, which will re- sult in the increase of greenhouse gas emission and pose ever increasing urgency on the environmental protection and sustainable network development. Thus, energy-efficiency is one of the most important rules that 5G network planning and design should follow. This dissertation presents power-aware planning and design for next generation wireless networks. We study network planning and design problems in both offline planning and online resource allocation. We propose approximation algo- rithms and effective heuristics for various network design scenarios, with different wireless network setups and different power saving optimization objectives. We aim to save power consumption on both base stations (BSs) and user equipments (UEs) by leveraging wireless relay placement, small cell deployment, device-to- device communications and base station consolidation. We first study a joint signal-aware relay station placement and power alloca- tion problem with consideration for multiple related physical constraints such as channel capacity, signal to noise ratio requirement of subscribers, relay power and network topology in multihop wireless relay networks. We present approximation schemes which first find a minimum number of relay stations, using maximum transmit power, to cover all the subscribers meeting each SNR requirement, and then ensure communications between any subscriber and a base station by ad- justing the transmit power of each relay station. In order to save power on BS, we propose a practical solution and offer a new perspective on implementing green wireless networks by embracing small cell networks. Many existing works have proposed to schedule base station into sleep to save energy. However, in reality, it is very difficult to shut down and reboot BSs frequently due to nu- merous technical issues and performance requirements. Instead of putting BSs into sleep, we tactically reduce the coverage of each base station, and strategi- cally place microcells to offload the traffic transmitted to/from BSs to save total power consumption. In online resource allocation, we aim to save tranmit power of UEs by en- abling device-to-device (D2D) communications in OFDMA-based wireless net- works. Most existing works on D2D communications either targeted CDMA- based single-channel networks or aimed at maximizing network throughput. We formally define an optimization problem based on a practical link data rate model, whose objective is to minimize total power consumption while meeting user data rate requirements. We propose to solve it using a joint optimization approach by presenting two effective and efficient algorithms, which both jointly determine mode selection, channel allocation and power assignment. In the last part of this dissertation, we propose to leverage load migration and base station consolidation for green communications and consider a power- efficient network planning problem in virtualized cognitive radio networks with the objective of minimizing total power consumption while meeting traffic load demand of each Mobile Virtual Network Operator (MVNO). First we present a Mixed Integer Linear Programming (MILP) to provide optimal solutions. Then we present a general optimization framework to guide algorithm design, which solves two subproblems, channel assignment and load allocation, in sequence. In addition, we present an effective heuristic algorithm that jointly solves the two subproblems. Numerical results are presented to confirm the theoretical analysis of our schemes, and to show strong performances of our solutions, compared to several baseline methods

Inhibitory effects of berry anthocyanins on palmitic acid- or lipopolysaccharide- induced inflammation in human preadipocytes

Obesity is an inflammatory disease associated with the development and progression of chronic degenerative diseases including insulin resistance, cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and cancer. Circulating free fatty acid (FFA) are known risk factors promoting inflammation that can lead to CVD. Pre/adipocytes are known storage of low grade inflammatory biomarkers associated with obesity. However, the effects of dietary anthocyanins on inflammatory biomarkers in preadipocytes have not been reported. Berries are rich sources of naturally occurring antioxidant polyphenolics. There is increasing interest in the ability of berry anthocyanins to provide health benefits against obesity. Anthocyanins were isolated from blueberry, blackberry, cranberry and black currant and analyzed by spectrophotometry and liquid chromatography. The objective of this study was to test the effect of berry anthocyanins on palmitic acid (PA)-induced inflammatory biomarkers in human preadipocytes. Comparison was made with the effect of berry anthocyanins on lipopolysaccharide (LPS)-induced inflammation in similar human preadipocytes. Preadipocytes from obese women were incubated with different concentrations (10-40ìM) of berry anthocyanins for 24 h followed by addition of 100 ìM PA and additional incubation for 24h or 100ng/ml of LPS for 8 h. In another treatment, preadipocytes were incubated with 100 ìM PA for 24h or 100ng/ml of LPS for 8 h and then incubated with 10-40ìM anthocyanins for 24h. All incubations were performed at 37 °C in a 5% CO2 humidified incubator. Pro-inflammatory cytokines IL-6, IL-8 and MCP-1 were analyzed in conditioned preadipocyte media by ELISA. NF-êB and COX-2 from preadipocyte lysates were analyzed by Western Blot. PA or LPS induced up-regulation of the pro-inflammatory biomarkers. Berry anthocyanins significantly inhibited PA- or LPS-induced inflammation when anthocyanins were added to the preadipocytes prior to PA or LPS addition. However, the same anthocyanins were weak inhibitors of PA- or LPS-induced inflammation when preadipocytes were first incubated with LPS or PA. The results of our investigation show that berry anthocyanins may be effective in preventing PA- or LPS-induced low-grade inflammation in preadipocytes

Oat consumption reduced intestinal fat deposition and improved health span in Caenorhabditis elegans model

© 2015 The Authors. In addition to their fermentable dietary fiber and the soluble β-glucan fiber, oats have unique avenanthramides that have anti-inflammatory and antioxidant properties that reduce coronary heart disease in human clinical trials. We hypothesized that oat consumption will increase insulin sensitivity, reduce body fat, and improve health span in Caenorhabditis elegans through a mechanism involving the daf-2 gene, which codes for the insulin/insulin-like growth factor-1-like receptor, and that hyperglycemia will attenuate these changes. Caenorhabditis elegans wild type (N2) and the null strains sir-2.1, daf-16, and daf-16/daf-2 were fed Escherichia coli (OP50) and oat flakes (0.5%, 1.0%, or 3%) with and without 2% glucose. Oat feeding decreased intestinal fat deposition in N2, daf-16, or daf-16/daf-2 strains (P \u3c.05); and glucose did not affect intestinal fat deposition response. The N2, daf-16, or sir-2.1 mutant increased the pharyngeal pumping rate (P \u3c.05), a surrogate marker of life span, following oat consumption. Oat consumption increased ckr-1, gcy-8, cpt-1, and cpt-2 mRNA expression in both the N2 and the sir-2.1 mutant, with significantly higher expression in sir-2.1 than in N2 (P \u3c.01). Additional glucose further increased expression 1.5-fold of the 4 genes in N2 (P \u3c.01), decreased the expression of all except cpt-1 in the daf-16 mutant, and reduced mRNA expression of the 4 genes in the daf-16/daf-2 mutant (P \u3c.01). These data suggest that oat consumption reduced fat storage and increased ckr-1, gcy-8, cpt-1, or cpt-2 through the sir-2.1 genetic pathway. Oat consumption may be a beneficial dietary intervention for reducing fat accumulation, augmenting health span, and improving hyperglycemia-impaired lipid metabolism

Mapping the path towards novel treatment strategies: a bibliometric analysis of Hashimoto’s thyroiditis research from 1990 to 2023

BackgroundHashimoto’s thyroiditis (HT), a common form of thyroid autoimmunity, is strongly associated with deteriorating clinical status and impaired quality of life. The escalating global prevalence, coupled with the complexity of disease mechanisms, necessitates a comprehensive, bibliometric analysis to elucidate the trajectory, hotspots, and future trends in HT research.ObjectiveThis study aims to illuminate the development, hotspots, and future directions in HT research through systematic analysis of publications, institutions, authors, journals, references, and keywords. Particular emphasis is placed on novel treatment strategies for HT and its complications, highlighting the potential role of genetic profiling and immunomodulatory therapies.MethodsWe retrieved 8,726 relevant documents from the Web of Science Core Collection database spanning from 1 January 1990 to 7 March 2023. Following the selection of document type, 7,624 articles were included for bibliometric analysis using CiteSpace, VOSviewer, and R software.ResultsThe temporal evolution of HT research is categorized into three distinct phases: exploration (1990-1999), rapid development (1999-2000), and steady growth (2000-present). Notably, the United States, China, Italy, and Japan collectively contributed over half (54.77%) of global publications. Among the top 10 research institutions, four were from Italy (4/10), followed by China (2/10) and the United States (2/10). Recent hotspots, such as the roles of gut microbiota, genetic profiling, and nutritional factors in HT management, the diagnostic dilemmas between HT and Grave’s disease, as well as the challenges in managing HT complicated by papillary thyroid carcinoma and type 1 diabetes mellitus, are discussed.ConclusionAlthough North America and Europe have a considerable academic impact, institutions from emerging countries like China are demonstrating promising potential in HT research. Future studies are anticipated to delve deeper into the differential diagnosis of HT and Grave’s disease, the intricate relationship between gut microbiota and HT pathogenesis, clinical management of HT with papillary thyroid carcinoma or type 1 diabetes, and the beneficial effects of dietary modifications and micronutrients supplementation in HT. Furthermore, the advent of genetic profiling and advanced immunotherapies for managing HT offers promising avenues for future research

SOCS3 Expression by Thymic Stromal Cells Is Required for Normal T Cell Development

The suppressor of cytokine signaling 3 (SOCS3) is a major regulator of immune responses and inflammation as it negatively regulates cytokine signaling. Here, the role of SOCS3 in thymic T cell formation was studied in Socs3fl/fl Actin-creER mice (Δsocs3) with a tamoxifen inducible and ubiquitous Socs3 deficiency. Δsocs3 thymi showed a 90% loss of cellularity and altered cortico-medullary organization. Thymocyte differentiation and proliferation was impaired at the early double negative (CD4-CD8-) cell stage and apoptosis was increased during the double positive (CD4+CD8+) cell stage, resulting in the reduction of recent thymic emigrants in peripheral organs. Using bone marrow chimeras, transplanting thymic organoids and using mice deficient of SOCS3 in thymocytes we found that expression in thymic stromal cells rather than in thymocytes was critical for T cell development. We found that SOCS3 in thymic epithelial cells (TECs) binds to the E3 ubiquitin ligase TRIM 21 and that Trim21−/− mice showed increased thymic cellularity. Δsocs3 TECs showed alterations in the expression of genes involved in positive and negative selection and lympho-stromal interactions. SOCS3-dependent signal inhibition of the common gp130 subunit of the IL-6 receptor family was redundant for T cell formation. Together, SOCS3 expression in thymic stroma cells is critical for T cell development and for maintenance of thymus architecture.publishedVersio

Lower Doses of Fructose Extend Lifespan in Caenorhabditis elegans

© 2017, Copyright © Taylor & Francis Group, LLC. Epidemiological studies indicate that the increased consumption of sugars including sucrose and fructose in beverages correlate with the prevalence of obesity, type-2 diabetes, insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension in humans. A few reports suggest that fructose extends lifespan in Saccharomyces cerevisiae. In Anopheles gambiae, fructose, glucose, or glucose plus fructose also extended lifespan. New results presented here suggest that fructose extends lifespan in Caenorhabditis elegans (C. elegans) wild type (N2). C. elegans were fed standard laboratory food source (E. coli OP50), maintained in liquid culture. Experimental groups received additional glucose (111 mM), fructose (55 mM, 111 mM, or 555 mM), sucrose (55 mM, 111 mM, or 555 mM), glucose (167 mM) plus fructose (167 mM) (G&F), or high fructose corn syrup (HFCS, 333 mM). In four replicate experiments, fructose dose-dependently increased mean lifespan at 55 mM or 111 m Min N2, but decreased lifespan at 555 mM (P \u3c 0.001). Sucrose did not affect the lifespan. Glucose reduced lifespan (P \u3c 0.001). Equal amount of G&F or HFCS reduced lifespan (P \u3c 0.0001). Intestinal fat deposition (IFD) was increased at a higher dose of fructose (555 mM), glucose (111 mM), and sucrose (55 mM, 111 mM, and 555 mM). Here we report a biphasic effect of fructose increasing lifespan at lower doses and shortening lifespan at higher doses with an inverse effect on IFD. In view of reports that fructose increases lifespan in yeast, mosquitoes and now nematodes, while decreasing fat deposition (in nematodes) at lower concentrations, further research into the relationship of fructose to lifespan and fat accumulation in vertebrates and mammals is indicated

Genome-Wide Analysis of Histone H3 Lysine9 Modifications in Human Mesenchymal Stem Cell Osteogenic Differentiation

Mesenchymal stem cells (MSCs) possess self-renewal and multi-lineage differentiation potentials. It has been established that epigenetic mechanisms such as histone modifications could be critical for determining the fate of stem cells. In this study, full human genome promoter microarrays and expression microarrays were used to explore the roles of histone modifications (H3K9Ac and H3K9Me2) upon the induction of MSC osteogenic differentiation. Our results revealed that the enrichment of H3K9Ac was decreased globally at the gene promoters, whereas the number of promoters enriched with H3K9Me2 was increased evidently upon osteogenic induction. By a combined analysis of data from both ChIP-on-chip and expression microarrays, a number of differentially expressed genes regulated by H3K9Ac and/or H3K9Me2 were identified, implicating their roles in several biological events, such as cell cycle withdraw and cytoskeleton reconstruction that were essential to differentiation process. In addition, our results showed that the vitamin D receptor played a trans-repression role via alternations of H3K9Ac and H3K9Me2 upon MSC osteogenic differentiation. Data from this study suggested that gene activation and silencing controlled by changes of H3K9Ac and H3K9Me2, respectively, were crucial to MSC osteogenic differentiation

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Joint mode selection, channel allocation and power assignment for green device-to-device communications

Device-to-Device (D2D) communication has emerged as a promising technique for improving capacity and reducing power consumption in wireless networks. Most existing works on D2D communications either targeted CDMA-based singlechannel networks or aimed to maximize network throughput. In this paper, we, however, aim at enabling green D2D communications in OFDMA-based wireless networks. We formally define an optimization problem based on a practical link data rate model, whose objective is to minimize power consumption while meeting user data rate requirements. We then present an effective algorithm to solve it in polynomial time, which jointly determines mode selection, channel allocation and power assignment. It has been shown by extensive simulation results that the proposed algorithm can achieve over 57% power savings, compared to several baseline methods. 2014 IEEE.Scopus2-s2.0-8490699550