Circadian rhythms of biliary protein and lipid excretion in rats

To gain insight into the mechanisms by which hepatocytes release lipids and proteins into bile, we studied extended, steady-state secretion of bile, lipids, and lysosomal and canalicular membrane proteins in freely moving, unanesthetized rats with chronic bile fistulas. We found circadian rhythms of biliary secretion for all measured constituents. In the basal state (nocturnal feeding), two distinct secretory patterns emerged: type 1, characterized by a peak at midnight and a nadir at noon; and type 2, characterized by a peak at 8 A.M. and a nadir at 8 P.M. We observed parallel, type 1 circadian rhythms of excretion for bile, biliary lipids (bile acid, cholesterol, phospholipid), and a canalicular membrane enzyme (alkaline phosphodiesterase I). In contrast, a type 2 circadian rhythm was observed for the outputs of two lysosomal enzymes. Hepatic lysosomal enzyme concentrations and the number of pericanalicular lysosomes decreased (P less than 0.05) by 15 and 35%, respectively, at the nadir of their biliary output relative to the time of their peak outputs. In response to daytime feeding, major shifts in the circadian rhythms of excretion of biliary constituents occurred such that secretion of bile, lipids, and the canalicular membrane protein adopted a type 2-like rhythm, whereas the biliary secretion of the lysosomal proteins exhibited a type 1-like pattern. These results indicate that bile flow and biliary excretion of individual lipids and proteins exhibit distinct circadian rhythms that are altered by feeding. Secretory events at the canaliculus that depend on the transmembrane flux of bile acids, such as water and lipid movement or the solubilization of membrane proteins, display a common rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

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Can Smart Pens Help Improve Diabetes Management?

Journal of Diabetes Science and Technology ◽

10.1177/1932296820965600 ◽

2020 ◽

pp. 193229682096560

Author(s):

Sarah L. Sy ◽

Medha M. Munshi ◽

Elena Toschi

Keyword(s):

Physical Activity ◽

Bolus Dose ◽

Diabetes Management ◽

Mobile Apps ◽

The Past ◽

Continuous Glucose Monitors ◽

The Relationship ◽

Insight Into

Smart pen technology has evolved over the past decade with new features such as Bluetooth connectivity, bolus dose calculators, and integration with mobile apps and continuous glucose monitors. While similar in appearance to a traditional insulin pen, smart pens have the ability to record and store data of insulin injections. These devices have the potential to transform diabetes management for clinicians, and patients with type 1 and type 2 diabetes on insulin therapy by improving adherence, glycemic control, and addressing barriers to diabetes management. Smart pens can also highlight the relationship between insulin, food, and physical activity, and provide insight into optimizing insulin regimens. Education of clinicians and patients, and more clinical studies showing the benefits of smart pens and cost-effectiveness, are needed.

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A key role for IL-13 signaling via the type 2 IL-4 receptor in experimental atopic dermatitis

Science Immunology ◽

10.1126/sciimmunol.aaw2938 ◽

2020 ◽

Vol 5 (44) ◽

pp. eaaw2938 ◽

Cited By ~ 5

Author(s):

Almog Bitton ◽

Shmuel Avlas ◽

Hadar Reichman ◽

Michal Itan ◽

Danielle Karo-Atar ◽

...

Keyword(s):

Atopic Dermatitis ◽

Allergic Diseases ◽

Proof Of Concept ◽

Potential Therapeutic Target ◽

Tnf Α ◽

Allergic Skin ◽

Insight Into

IL-13 and IL-4 are potent mediators of type 2–associated inflammation such as those found in atopic dermatitis (AD). IL-4 shares overlapping biological functions with IL-13, a finding that is mainly explained by their ability to signal via the type 2 IL-4 receptor (R), which is composed of IL-4Rα in association with IL-13Rα1. Nonetheless, the role of the type 2 IL-4R in AD remains to be clearly defined. Induction of two distinct models of experimental AD in Il13ra1−/− mice, which lack the type 2 IL-4R, revealed that dermatitis, including ear and epidermal thickening, was dependent on type 2 IL-4R signaling. Expression of TNF-α was dependent on the type 2 IL-4R, whereas induction of IL-4, IgE, CCL24, and skin eosinophilia was dependent on the type 1 IL-4R. Neutralization of IL-4, IL-13, and TNF-α as well as studies in bone marrow–chimeric mice revealed that dermatitis, TNF-α, CXCL1, and CCL11 expression were exclusively mediated by IL-13 signaling via the type 2 IL-4R expressed by nonhematopoietic cells. Conversely, induction of IL-4, CCL24, and eosinophilia was dependent on IL-4 signaling via the type 1 IL-4R expressed by hematopoietic cells. Last, we pharmacologically targeted IL-13Rα1 and established a proof of concept for therapeutic targeting of this pathway in AD. Our data provide mechanistic insight into the differential roles of IL-4, IL-13, and their receptor components in allergic skin and highlight type 2 IL-4R as a potential therapeutic target in AD and other allergic diseases such as asthma and eosinophilic esophagitis.

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Epigenetic Control of Pancreatic Regeneration in Diabetes

Genes ◽

10.3390/genes9090448 ◽

2018 ◽

Vol 9 (9) ◽

pp. 448 ◽

Cited By ~ 1

Author(s):

Shruti Balaji ◽

Tiziana Napolitano ◽

Serena Silvano ◽

Marika Friano ◽

Anna Garrido-Utrilla ◽

...

Keyword(s):

Molecular Mechanisms ◽

Β Cells ◽

Β Cell ◽

Pancreatic Cells ◽

Current Review ◽

Cell Sources ◽

Active Research ◽

Insight Into

Both type 1 and type 2 diabetes are conditions that are associated with the loss of insulin-producing β-cells within the pancreas. An active research therefore aims at regenerating these β-cells with the hope that they could restore euglycemia. The approaches classically used consist in mimicking embryonic development, making use of diverse cell sources or converting pre-existing pancreatic cells. Despite impressive progresses and promising successes, it appears that we still need to gain further insight into the molecular mechanisms underlying β-cell development. This becomes even more obvious with the emergence of a relatively new field of research, epigenetics. The current review therefore focuses on the latest advances in this field in the context of β-cell (neo-)genesis research.

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Discovering the Role of Emotional and Rational Appeals and Hidden Heterogeneity of Consumers in Advertising Copies for Sustainable Marketing

Sustainability ◽

10.3390/su12125189 ◽

2020 ◽

Vol 12 (12) ◽

pp. 5189 ◽

Cited By ~ 2

Author(s):

Cheong Kim ◽

Hyeon Gyu Jeon ◽

Kun Chang Lee

Keyword(s):

Unobserved Heterogeneity ◽

Practical Implication ◽

Marketing Strategies ◽

Consumer Group ◽

Sustainable Marketing ◽

Type 3 ◽

Insight Into

Advertising copies have been considered as a fundamental strategy for firms to continue sustainable marketing strategies. In order to provide the advancement of previous research and practical implication to marketers in the field for sustainable marketing strategy, this research tried to reveal the role of emotional and rational appeals as well as hidden heterogeneity of consumers in the appeal–value–trust–satisfaction–WOM framework. By applying the PLS-SEM and PLS-POS approach to 230 valid questionnaire samples, we could discover the role of appeals in the framework as well as three types of unobserved heterogeneity among the respondents. Both emotional and rational appeals had significant influences on the value–satisfaction–trust–WOM context. In addition, for hidden consumer traits in advertising copies, we revealed three types of consumer groups: Type 1, the consumer group with a rational orientation (n = 68); Type 2, the group with an emotional orientation (n = 74) and Type 3, the group with a utilitarian orientation. This research provided contributions by offering some insight into ways to establish sustainable marketing strategies in advertisements and to address unobserved heterogeneity consumers in advertising copy appeals.

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Networking Opportunities: The Friedel Crafts Reaction

Reactions ◽

10.1093/oso/9780199695126.003.0027 ◽

2011 ◽

Author(s):

Peter Atkins

Keyword(s):

Chloride Ion ◽

Benzene Molecule ◽

Electron Cloud ◽

Aluminium Chloride ◽

Cl Atoms ◽

Cl Atom ◽

Insight Into ◽

Positively Charged

In the final reaction of this part I am going to help you extend your ability to use our toolkit to build a network of carbon atoms. The reaction I talk about here is one of many that I could have chosen and will give you some insight into the way that organic chemists go about building their intricate constructions. It was devised in 1877 by the French chemist Charles Friedel (1832–1899) and the American chemist James Crafts (1839–1917). There are two kinds of Friedel–Crafts reaction: I shall call them Type 1 and Type 2. The latter is more important, but the former is a bit simpler and I shall deal with it first. In a Type 1 Friedel–Crafts reaction, the aim is to attach a group of C atoms, such as 1, to a benzene ring or a related molecule. The strategy is to generate a powerful electrophile (Reaction 16), one characteristic of the group of atoms you want to attach, which will seek out regions of dense electron cloud in the target benzene molecule. The tactics involve taking the group you want to attach in combination with a chlorine atom, Cl, as in 2, and then finding another dentist-like compound that will extract the Cl atom as a chloride ion, Cl–. That extraction will leave a positively charged hydrocarbon ion hungry for opposite charge and thus able to act as the electrophile. The Friedel–Crafts procedure uses aluminium chloride, 3, to act as this dentist compound. It gets regenerated in the reaction, so it is present as a catalyst (Reaction 11). When you examine this molecule you see that although its Cl atoms are rich in electrons, the aluminium atom, Al, has a very skimpy share in them and the positive charge of its nucleus shines through. Moreover, the molecule is flat, and there is plenty of room for the Cl atoms to bend away from any incoming intruder atom and so make room for its attachment to the Al atom.

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Metabolomics of Type 1 and Type 2 Diabetes

International Journal of Molecular Sciences ◽

10.3390/ijms20102467 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2467 ◽

Cited By ~ 27

Author(s):

Borros Arneth ◽

Rebekka Arneth ◽

Mohamed Shams

Keyword(s):

Type 2 Diabetes ◽

Amino Acids ◽

Reference Lists ◽

Aromatic Amino Acids ◽

Plasma Metabolites ◽

Effective Interventions ◽

Care Costs ◽

Insight Into

Type 1 and type 2 diabetes mellitus (DM) are chronic diseases that affect nearly 425 million people worldwide, leading to poor health outcomes and high health care costs. High-throughput metabolomics screening can provide vital insight into the pathophysiological pathways of DM and help in managing its effects. The primary aim of this study was to contribute to the understanding and management of DM by providing reliable evidence of the relationships between metabolites and type 1 diabetes (T1D) and metabolites and type 2 diabetes (T2D). Information for the study was obtained from the PubMed, MEDLINE, and EMBASE databases, and leads to additional articles that were obtained from the reference lists of the studies examined. The results from the selected studies were used to assess the relationships between diabetes (T1D and/or T2D) and metabolite markers—such as glutamine, glycine, and aromatic amino acids—in patients. Seventy studies were selected from the three databases and from the reference lists in the records retrieved. All studies explored associations between various metabolites and T1D or T2D. This review identified several plasma metabolites associated with T2D prediabetes and/or T1D and/or T2D in humans. The evidence shows that metabolites such as glucose, fructose, amino acids, and lipids are typically altered in individuals with T1D and T2D. These metabolites exhibit significant predictive associations with T2D prediabetes, T1D, and/or T2D. The current review suggests that changes in plasma metabolites can be identified by metabolomic techniques and used to identify and analyze T1D and T2D biomarkers. The results of the metabolomic studies can be used to help create effective interventions for managing these diseases.

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