On the phage side, while it is true that the vast majority of known phages have DNA genomes, the bias of sequencing exclusively DNA has served as a self-reinforcing positive feedback loop; however, ...recent studies examining samples that have sequenced RNA have demonstrated that there is a much greater abundance and diversity of RNA phages in the world 13. ...in order achieve a more complete view of the virome, it is critical that virome studies be designed such that RNA viruses are preserved in the specimens and that the RNA fraction is incorporated into the sequencing and analysis. ...for phages, genomic sequences of thousands of novel phages can be identified in a single study 16, 17, but very few have been isolated 18. ...while (in the past) discovery of novel viruses was rate limiting, today the rate-limiting step has shifted to development of culture systems for the viruses that have been molecularly identified. In part, it is challenging for labs to obtain funding to culture novel viruses, particularly in the absence of any strong disease association. ...the risk of a negative result, exemplified by many decades of unsuccessful attempts to culture human norovirus, is substantial. On the phage front, one significant challenge is that many of the bacterial host species are themselves unculturable using standard bacterial-growth media. ...efforts to propagate novel phages will also entail improving systems for bacterial in vitro growth.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AbstractAtherosclerosis is characterized by lipid accumulation, inflammatory response, cell death and fibrosis in the arterial wall, and is a major pathological basis for ischemic coronary heart ...disease (CHD), which is the leading cause of morbidity and mortality in the USA and Europe. Intervention studies with statins have shown to reduce plasma LDL cholesterol concentrations and subsequently the risk of developing CHD. However, not all the aggressive statin therapy could decrease the risk of developing CHD. Many clinical and epidemiological studies have clearly demonstrated that the HDL cholesterol is inversely associated with risk of CHD and is a critical and independent component of predicting this risk. Elucidations of HDL metabolism give rise to therapeutic targets with potential to raising plasma HDL cholesterol levels, thereby reducing the risk of developing CHD. The concept of reverse cholesterol transport is based on the hypothesis that HDL displays an cardioprotective function, which is a process involved in the removal of excess cholesterol that is accumulated in the peripheral tissues (e.g., macrophages in the aortae) by HDL, transporting it to the liver for excretion into the feces via the bile. In this review, we summarize the latest advances in the role of the lymphatic route in reverse cholesterol transport, as well as the biliary and the non-biliary pathways for removal of cholesterol from the body. These studies will greatly increase the likelihood of discovering new lipid-lowering drugs, which are more effective in the prevention and therapeutic intervention of CHD that is the major cause of human death and disability worldwide.
Bile Acid Physiology Di Ciaula, Agostino; Garruti, Gabriella; Lunardi Baccetto, Raquel ...
Annals of hepatology,
11/2017, Letnik:
16, Številka:
Suppl. 1: s3-105.
Journal Article
Recenzirano
Odprti dostop
AbstractThe primary bile acids (BAs) are synthetized from cholesterol in the liver, conjugated to glycine or taurine to increase their solubility, secreted into bile, concentrated in the gallbladder ...during fasting, and expelled in the intestine in response to dietary fat. BAs are also bio-transformed in the colon to the secondary BAs by the gut microbiota, reabsorbed in the ileum and colon back to the liver, and minimally lost in the feces. BAs in the intestine not only regulate the digestion and absorption of cholesterol, triglycerides, and fat-soluble vitamins, but also play a key role as signaling molecules in modulating epithelial cell proliferation, gene expression, and lipid and glucose metabolismby activating farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor-1 (GPBAR-1, also known as TGR5) in the liver, intestine, muscle and brown adipose tissue. Recent studies have revealed the metabolic pathways of FXR and GPBAR-1 involved in the biosynthesis and enterohepatic circulation of BAs and their functions as signaling molecules on lipid and glucose metabolism.
Gut microbiota encompasses a wide variety of commensal microorganisms consisting of trillions of bacteria, fungi, and viruses. This microbial population coexists in symbiosis with the host, and ...related metabolites have profound effects on human health. In this respect, gut microbiota plays a pivotal role in the regulation of metabolic, endocrine, and immune functions. Bacterial metabolites include the short chain fatty acids (SCFAs) acetate (C2), propionate (C3), and butyrate (C4), which are the most abundant SCFAs in the human body and the most abundant anions in the colon. SCFAs are made from fermentation of dietary fiber and resistant starch in the gut. They modulate several metabolic pathways and are involved in obesity, insulin resistance, and type 2 diabetes. Thus, diet might influence gut microbiota composition and activity, SCFAs production, and metabolic effects. In this narrative review, we discuss the relevant research focusing on the relationship between gut microbiota, SCFAs, and glucose metabolism.
•We address the optimal location of multiple types of BEV charging facilities, including dynamic wireless charging facilities and different levels of plug-in charging stations.•A tri-level ...programming is developed to model the presented problem.•An efficient solution algorithm is proposed to solve the model, wherein the formulated model is first treated as a black-box optimization, and then solved by an efficient surface response approximation model based solution algorithm.
To reduce greenhouse gas emissions in transportation sector, battery electric vehicle (BEV) is a better choice towards the ultimate goal of zero-emission. However, the shortened range, extended recharging time and insufficient charging facilities hinder the wide adoption of BEV. Recently, a wireless power transfer technology, which can provide dynamic recharging when vehicles are moving on roadway, has the potential to solve these problems. The dynamic recharging facilities, if widely applied on road network, can allow travelers to drive in unlimited range without stopping to recharge. This paper aims to study the complex charging facilities location problem, assuming the wireless charging is technologically mature and a new type of wireless recharging BEV is available to be selected by consumers in the future other than the traditional BEV requiring fixed and static charging stations. The objective is to assist the government planners on optimally locating multiple types of BEV recharging facilities to satisfy the need of different BEV types within a given budget to minimize the public social cost. Road users’ ownership choice among multiple types BEV and BEV drivers’ routing choice behavior are both explicitly considered. A tri-level programming is then developed to model the presented problem. The formulated model is first treated as a black-box optimization, and then solved by an efficient surface response approximation model based solution algorithm.
PURPOSE OF REVIEWGallstone disease is a major epidemiologic and economic burden worldwide, and the most frequent form is cholesterol gallstone disease.
RECENT FINDINGSMajor pathogenetic factors for ...cholesterol gallstones include a genetic background, hepatic hypersecretion of cholesterol, and supersaturated bile which give life to precipitating cholesterol crystals that accumulate and grow in a sluggish gallbladder. Additional factors include mucin and inflammatory changes in the gallbladder, slow intestinal motility, increased intestinal absorption of cholesterol, and altered gut microbiota. Mechanisms of disease are linked with insulin resistance, obesity, the metabolic syndrome, and type 2 diabetes. The role of nuclear receptors, signaling pathways, gut microbiota, and epigenome are being actively investigated.
SUMMARYOngoing research on cholesterol gallstone disease is intensively investigating several pathogenic mechanisms, associated metabolic disorders, new therapeutic approaches, and novel strategies for primary prevention, including lifestyles.
Background
Dietary fat is one of the most important energy sources of all the nutrients. Fatty acids, stored as triacylglycerols (also called triglycerides) in the body, are an important reservoir of ...stored energy and derived primarily from animal fats and vegetable oils.
Design
Although the molecular mechanisms for the transport of water‐insoluble amphipathic fatty acids across cell membranes have been debated for many years, it is now believed that the dominant means for intestinal fatty acid uptake is via membrane‐associated fatty acid–binding proteins, that is, fatty acid transporters on the apical membrane of enterocytes.
Results
These findings indicate that intestinal fatty acid absorption is a multistep process that is regulated by multiple genes at the enterocyte level, and intestinal fatty acid absorption efficiency could be determined by factors influencing intraluminal fatty acid molecules across the brush border membrane of enterocytes. To facilitate research on intestinal, hepatic and plasma triacylglycerol metabolism, it is imperative to establish standard protocols for precisely and accurately measuring the efficiency of intestinal fatty acid absorption in humans and animal models. In this review, we will discuss the chemical structure and nomenclature of fatty acids and summarize recent progress in investigating the molecular mechanisms underlying the intestinal absorption of fatty acids, with a particular emphasis on the physical chemistry of intestinal lipids and the molecular physiology of intestinal fatty acid transporters.
Conclusions
A better understanding of the molecular mechanism of intestinal fatty acid absorption should lead to novel approaches to the treatment and the prevention of fatty acid–related metabolic diseases that are prevalent worldwide.
If memory hierarchy is stopping your microprocessor from performing at the highest level it should be, then this book will show how to resolve that problem. This book provides the reader with ...everything they need to know about the logical design and operation, physical design and operation, performance characteristics and resulting design trade-offs, and the energy consumption of modern memory hierarchies. You learn how to tackle the challenging optimization problems that result from the side-effects that can appear at any point in the entire hierarchy. As a result you will be able to design and emulate the entire memory hierarchy. As a reference, this book is targeted toward both academics and practicing engineers in microarchitecture and computer system design, embedded system design, and low power design.
•A mixed integer non linear programming model on ship routing and deployment is proposed.•Some important properties of the proposed problem are obtained.•A dynamic programming based method is ...developed.•The proposed model can contribute to cost savings.
This paper addresses a joint ship path, speed, and deployment problem in a liner shipping company considering three emission reduction measures, including sulfur emission regulations, carbon tax, and vessel speed reduction incentive programs (VSRIPs). Given a set of service routes and the total number of available ships, the proposed problem determines how many ships should be deployed on each route and how to design sailing path and speed for each leg. A mixed-integer non-linear programming model is presented for minimizing the total cost of all routes, i.e., fuel cost, carbon tax, and fixed cost, minus dockage refund. The different impacts of the three emission reduction measures on sailing path and speed complicate the problem. Some important properties are obtained by analyzing the proposed model. Combining these properties with a dynamic programming approach, a tailored method is developed to solve the problem. Based on real data, extensive numerical experiments are conducted to examine the validity of the proposed model and the efficiency of the solution method. The computational results demonstrate that the proposed model can contribute to significant cost savings for shipping companies.
Bile acids (BA) are amphiphilic molecules synthesized in the liver (primary BA) starting from cholesterol. In the small intestine, BA act as strong detergents for emulsification, solubilization and ...absorption of dietary fat, cholesterol, and lipid-soluble vitamins. Primary BA escaping the active ileal re-absorption undergo the microbiota-dependent biotransformation to secondary BA in the colon, and passive diffusion into the portal vein towards the liver. BA also act as signaling molecules able to play a systemic role in a variety of metabolic functions, mainly through the activation of nuclear and membrane-associated receptors in the intestine, gallbladder, and liver. BA homeostasis is tightly controlled by a complex interplay with the nuclear receptor farnesoid X receptor (FXR), the enterokine hormone fibroblast growth factor 15 (FGF15) or the human ortholog FGF19 (FGF19). Circulating FGF19 to the FGFR4/β-Klotho receptor causes smooth muscle relaxation and refilling of the gallbladder. In the liver the binding activates the FXR-small heterodimer partner (SHP) pathway. This step suppresses the unnecessary BA synthesis and promotes the continuous enterohepatic circulation of BAs. Besides BA homeostasis, the BA-FXR-FGF19 axis governs several metabolic processes, hepatic protein, and glycogen synthesis, without inducing lipogenesis. These pathways can be disrupted in cholestasis, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Thus, targeting FXR activity can represent a novel therapeutic approach for the prevention and the treatment of liver and metabolic diseases.
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