Sex differences in lifespan extension with acarbose and 17‐α estradiol: gonadal hormones underlie male‐specific improvements in glucose tolerance and mTORC2 signaling

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140036/1/acel12656.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140036/2/acel12656_am.pd

ScreenTrack: Using a Visual History of a Computer Screen to Retrieve Documents and Web Pages

Computers are used for various purposes, so frequent context switching is inevitable. In this setting, retrieving the documents, files, and web pages that have been used for a task can be a challenge. While modern applications provide a history of recent documents for users to resume work, this is not sufficient to retrieve all the digital resources relevant to a given primary document. The histories currently available do not take into account the complex dependencies among resources across applications. To address this problem, we tested the idea of using a visual history of a computer screen to retrieve digital resources within a few days of their use through the development of ScreenTrack. ScreenTrack is software that captures screenshots of a computer at regular intervals. It then generates a time-lapse video from the captured screenshots and lets users retrieve a recently opened document or web page from a screenshot after recognizing the resource by its appearance. A controlled user study found that participants were able to retrieve requested information more quickly with ScreenTrack than under the baseline condition with existing tools. A follow-up study showed that the participants used ScreenTrack to retrieve previously used resources and to recover the context for task resumption.Comment: CHI 2020, 10 pages, 7 figure

Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer

The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin – the latter with and without rapamycin, and two drugs previously examined: 17-α-estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously. 17-α-estradiol at a threefold higher dose robustly extended both median and maximal lifespan, but still only in males. The male-specific extension of median lifespan by NDGA was replicated at the original dose, and using doses threefold lower and higher. The effects of NDGA were dose dependent and male specific but without an effect on maximal lifespan. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit, based on historical comparison with earlier studies of rapamycin given alone. The α-glucosidase inhibitor, acarbose, at a concentration previously tested (1000 ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16 months. Neither fish oil nor UDCA extended lifespan. These results underscore the reproducibility of ITP longevity studies and illustrate the importance of identifying optimal doses in lifespan studies

Induction of autophagy by spermidine promotes longevity.

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High fat diet enhances stemness and tumorigenicity of intestinal progenitors

Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we find that high fat diet (HFD)-induced obesity augments the numbers and function of Lgr5+ intestinal stem-cells (ISCs) of the mammalian intestine. Mechanistically, HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-d) signature in intestinal stem and (non-ISC) progenitor cells, and pharmacologic activation of PPAR-d recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-d dependent manner. Interestingly, HFD- and agonist-activated PPAR-d signaling endow organoid-initiating capacity to progenitors, and enforced PPAR-d signaling permits these progenitors to form in vivo tumors upon loss of the tumor suppressor Apc. These findings highlight how diet-modulated PPAR-d activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumors

PEPYS: Generating Autobiographies by . . .

This paper presents one part of a broad research project entitled `Activity-Based Information Retrieval' (AIR) which is being carried out at EuroPARC. The basic hypothesis of this project is that if contextual data about human activities can be automatically captured and later presented as recognisable descriptions of past episodes, then human memory of those past episodes can be improved. This paper describes an application called Pepys, designed to yield descriptions of episodes based on automatically collected location data. The program pays particular attention to meetings and other episodes involving two or more people. The episodes are presented to the user as a diary generated at the end of each day and distributed by electronic mail. The paper also discusses the methods used to assess the accuracy of the descriptions generated by the recogniser

Pepys: Generating Autobiographies by Automatic Tracking

Information Retrieval ’ (AIR) which is being carried out at EuroPARC. The basic hypothesis of this project is that if contextual data about human activities can be automatically captured and later presented as recognisable descriptions of past episodes, then human memory of those past episodes can be improved. This paper describes an application called Pepys, designed to yield descriptions of episodes based on automatically collected location data. The program pays particular attention to meetings and other episodes involving two or more people. The episodes are presented to the user as a diary generated at the end of each day and distributed by electronic mail. The paper also discusses the methods used to assess the accuracy of the descriptions generated by the recogniser

Two-Dimensional Frameworks Based on Ag(I)–N Bond Formation: Single Crystal to Single Molecular Sheet Transformation

A series of new two-dimensional coordination framework materials, based on Ag­(I)–N bond formation, has been synthesized and structurally characterized by single crystal methods. Reactions between the poly-monodentate bridging ligand <i>N</i>,<i>N</i>′-((1r,4r)-cyclohexane-1,4-diyl)­bis­(1-(pyridin-3-yl)­methanimine), <b>L1</b>, and silver salts yield compounds {[Ag­(<b>L1</b>)­(MeCN)]­(CF₃SO₃^–)}_<i>n</i>, <b>1</b>, {[Ag­(<b>L1</b>)­(PF₂O₂^–)]·H₂O}_<i>n</i>, <b>2</b>, and {Ag₂(<b>L1</b>)­(tosylate)₂}_<i>n</i>, <b>3</b>. The frameworks of these materials exhibit two distinct net topologies: 3⁶.4⁶.5³ (<b>1</b> and <b>2</b>) and 4⁴.6² (<b>3</b>). In all cases, <b>L1</b> ligands are found to be fully saturated, in terms of metal ion binding, with both sets of pyridyl and imino N atoms involved, though in <b>1</b> and <b>2</b>, crystallographically independent <b>L1</b> moieties also display pyridyl-only binding. Either solvent (<b>1</b>) or the anion (<b>2</b> and <b>3</b>) acts as a terminal ligand to support interlayer interactions in the solid state. For <b>2</b> and <b>3</b> the molecular sheet orientation lies in the plane of the largest crystal face, indicating that crystal growth is preferentially driven by coordinate bond formation. Despite the relatively labile nature, typical of such Ag­(I)–N bonds, solvent-based exfoliation of crystals of <b>3</b> was shown to provide dispersions of large, μm², flakes which readily deposit on oxide surfaces as single-molecule sheets, as revealed by atomic force microscopy

Two-Dimensional Frameworks Based on Ag(I)–N Bond Formation: Single Crystal to Single Molecular Sheet Transformation

A series of new two-dimensional coordination framework materials, based on Ag­(I)–N bond formation, has been synthesized and structurally characterized by single crystal methods. Reactions between the poly-monodentate bridging ligand <i>N</i>,<i>N</i>′-((1r,4r)-cyclohexane-1,4-diyl)­bis­(1-(pyridin-3-yl)­methanimine), <b>L1</b>, and silver salts yield compounds {[Ag­(<b>L1</b>)­(MeCN)]­(CF₃SO₃^–)}_<i>n</i>, <b>1</b>, {[Ag­(<b>L1</b>)­(PF₂O₂^–)]·H₂O}_<i>n</i>, <b>2</b>, and {Ag₂(<b>L1</b>)­(tosylate)₂}_<i>n</i>, <b>3</b>. The frameworks of these materials exhibit two distinct net topologies: 3⁶.4⁶.5³ (<b>1</b> and <b>2</b>) and 4⁴.6² (<b>3</b>). In all cases, <b>L1</b> ligands are found to be fully saturated, in terms of metal ion binding, with both sets of pyridyl and imino N atoms involved, though in <b>1</b> and <b>2</b>, crystallographically independent <b>L1</b> moieties also display pyridyl-only binding. Either solvent (<b>1</b>) or the anion (<b>2</b> and <b>3</b>) acts as a terminal ligand to support interlayer interactions in the solid state. For <b>2</b> and <b>3</b> the molecular sheet orientation lies in the plane of the largest crystal face, indicating that crystal growth is preferentially driven by coordinate bond formation. Despite the relatively labile nature, typical of such Ag­(I)–N bonds, solvent-based exfoliation of crystals of <b>3</b> was shown to provide dispersions of large, μm², flakes which readily deposit on oxide surfaces as single-molecule sheets, as revealed by atomic force microscopy