Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

The FDA approved drug rapamycin increases lifespan in rodents and delays age-related dysfunction in rodents and humans. Nevertheless, important questions remain regarding the optimal dose, duration, and mechanisms of action in the context of healthy aging. Here we show that 3 months of rapamycin treatment is sufficient to increase life expectancy by up to 60% and improve measures of healthspan in middle-aged mice. This transient treatment is also associated with a remodeling of the microbiome, including dramatically increased prevalence of segmented filamentous bacteria in the small intestine. We also define a dose in female mice that does not extend lifespan, but is associated with a striking shift in cancer prevalence toward aggressive hematopoietic cancers and away from non-hematopoietic malignancies. These data suggest that a short-term rapamycin treatment late in life has persistent effects that can robustly delay aging, influence cancer prevalence, and modulate the microbiome.P30 AG013280 - NIA NIH HHS; T32 AG000057 - NIA NIH HH

Trematodes of the Great Barrier Reef, Australia: emerging patterns of diversity and richness in coral reef fishes

The Great Barrier Reef holds the richest array of marine life found anywhere in Australia, including a diverse and fascinating parasite fauna. Members of one group, the trematodes, occur as sexually mature adult worms in almost all Great Barrier Reef bony fish species. Although the first reports of these parasites were made 100 years ago, the fauna has been studied systematically for only the last 25 years. When the fauna was last reviewed in 1994 there were 94 species known from the Great Barrier Reef and it was predicted that there might be 2,270 in total. There are now 326 species reported for the region, suggesting that we are in a much improved position to make an accurate prediction of true trematode richness. Here we review the current state of knowledge of the fauna and the ways in which our understanding of this fascinating group is changing. Our best estimate of the true richness is now a range, 1,100–1,800 species. However there remains considerable scope for even these figures to be incorrect given that fewer than one-third of the fish species of the region have been examined for trematodes. Our goal is a comprehensive characterisation of this fauna, and we outline what work needs to be done to achieve this and discuss whether this goal is practically achievable or philosophically justifiable

Spectral Measures and Generating Series for Nimrep Graphs in Subfactor Theory II: SU(3)

We complete the computation of spectral measures for SU(3) nimrep graphs arising in subfactor theory, namely the SU(3) ADE graphs associated with SU(3) modular invariants and the McKay graphs of finite subgroups of SU(3). For the SU(2) graphs the spectral measures distill onto very special subsets of the semicircle/circle, whilst for the SU(3) graphs the spectral measures distill onto very special subsets of the discoid/torus. The theory of nimreps allows us to compute these measures precisely. We have previously determined spectral measures for some nimrep graphs arising in subfactor theory, particularly those associated with all SU(2) modular invariants, all subgroups of SU(2), the torus, SU(3), and some SU(3) graphs.Comment: 38 pages, 21 figure

An assessment of the carbon balance of Arctic tundra:Comparisons among observations, process models, and atmospheric inversions

Although Arctic tundra has been estimated to cover only 8% of the global land surface, the large and potentially labile carbon pools currently stored in tundra soils have the potential for large emissions of carbon (C) under a warming climate. These emissions as radiatively active greenhouse gases in the form of both CO<sub>2</sub> and CH<sub>4</sub> could amplify global warming. Given the potential sensitivity of these ecosystems to climate change and the expectation that the Arctic will experience appreciable warming over the next century, it is important to assess whether responses of C exchange in tundra regions are likely to enhance or mitigate warming. In this study we compared analyses of C exchange of Arctic tundra between 1990 and 2006 among observations, regional and global applications of process-based terrestrial biosphere models, and atmospheric inversion models. Syntheses of flux observations and inversion models indicate that the annual exchange of CO<sub>2</sub> between Arctic tundra and the atmosphere has large uncertainties that cannot be distinguished from neutral balance. The mean estimate from an ensemble of process-based model simulations suggests that Arctic tundra has acted as a sink for atmospheric CO<sub>2</sub> in recent decades, but based on the uncertainty estimates it cannot be determined with confidence whether these ecosystems represent a weak or a strong sink. Tundra was 0.6 °C warmer in the 2000s compared to the 1990s. The central estimates of the observations, process-based models, and inversion models each identify stronger sinks in the 2000s compared with the 1990s. Some of the process models indicate that this occurred because net primary production increased more in response to warming than heterotrophic respiration. Similarly, the observations and the applications of regional process-based models suggest that CH<sub>4</sub> emissions from Arctic tundra have increased from the 1990s to 2000s because of the sensitivity of CH<sub>4</sub> emissions to warmer temperatures. Based on our analyses of the estimates from observations, process-based models, and inversion models, we estimate that Arctic tundra was a sink for atmospheric CO<sub>2</sub> of 110 Tg C yr<sup>−1</sup> (uncertainty between a sink of 291 Tg C yr<sup>−1</sup> and a source of 80 Tg C yr<sup>−1</sup>) and a source of CH<sub>4</sub> to the atmosphere of 19 Tg C yr<sup>−1</sup> (uncertainty between sources of 8 and 29 Tg C yr<sup>−1</sup>). The suite of analyses conducted in this study indicate that it is important to reduce uncertainties in the observations, process-based models, and inversions in order to better understand the degree to which Arctic tundra is influencing atmospheric CO<sub>2</sub> and CH<sub>4</sub> concentrations. The reduction of uncertainties can be accomplished through (1) the strategic placement of more CO<sub>2</sub> and CH<sub>4</sub> monitoring stations to reduce uncertainties in inversions, (2) improved observation networks of ground-based measurements of CO<sub>2</sub> and CH<sub>4</sub> exchange to understand exchange in response to disturbance and across gradients of climatic and hydrological variability, and (3) the effective transfer of information from enhanced observation networks into process-based models to improve the simulation of CO<sub>2</sub> and CH<sub>4</sub> exchange from Arctic tundra to the atmosphere

Finding the Patient’s Voice Using Big Data: Analysis of Users’ Health-Related Concerns in the ChaCha Question-and-Answer Service (2009–2012)

Background: The development of effective health care and public health interventions requires a comprehensive understanding of the perceptions, concerns, and stated needs of health care consumers and the public at large. Big datasets from social media and question-and-answer services provide insight into the public’s health concerns and priorities without the financial, temporal, and spatial encumbrances of more traditional community-engagement methods and may prove a useful starting point for public-engagement health research (infodemiology). Objective: The objective of our study was to describe user characteristics and health-related queries of the ChaCha question-and-answer platform, and discuss how these data may be used to better understand the perceptions, concerns, and stated needs of health care consumers and the public at large. Methods: We conducted a retrospective automated textual analysis of anonymous user-generated queries submitted to ChaCha between January 2009 and November 2012. A total of 2.004 billion queries were read, of which 3.50% (70,083,796/2,004,243,249) were missing 1 or more data fields, leaving 1.934 billion complete lines of data for these analyses. Results: Males and females submitted roughly equal numbers of health queries, but content differed by sex. Questions from females predominantly focused on pregnancy, menstruation, and vaginal health. Questions from males predominantly focused on body image, drug use, and sexuality. Adolescents aged 12–19 years submitted more queries than any other age group. Their queries were largely centered on sexual and reproductive health, and pregnancy in particular. Conclusions: The private nature of the ChaCha service provided a perfect environment for maximum frankness among users, especially among adolescents posing sensitive health questions. Adolescents’ sexual health queries reveal knowledge gaps with serious, lifelong consequences. The nature of questions to the service provides opportunities for rapid understanding of health concerns and may lead to development of more effective tailored interventions. [J Med Internet Res 2016;18(3):e44

Maturation of oral feeding skills in preterm infants.

AIM: Safe and successful oral feeding requires proper maturation of sucking, swallowing and respiration. We hypothesized that oral feeding difficulties result from different temporal development of the musculatures implicated in these functions. METHODS: Sixteen medically stable preterm infants (26 to 29 weeks gestation, GA) were recruited. Specific feeding skills were monitored as indirect markers for the maturational process of oral feeding musculatures: rate of milk intake (mL/min); percent milk leakage (lip seal); sucking stage, rate (#/s) and suction/expression ratio; suction amplitude (mmHg), rate and slope (mmHg/s); sucking/swallowing ratio; percent occurrence of swallows at specific phases of respiration. Coefficients of variation (COV) were used as indices of functional stability. Infants, born at 26/27- and 28/29-week GA, were at similar postmenstrual ages (PMA) when taking 1-2 and 6-8 oral feedings per day. RESULTS: Over time, feeding efficiency and several skills improved, some decreased and others remained unchanged. Differences in COVs between the two GA groups demonstrated that, despite similar oral feeding outcomes, maturation levels of certain skills differed. CONCLUSIONS: Components of sucking, swallowing, respiration and their coordinated activity matured at different times and rates. Differences in functional stability of particular outcomes confirm that maturation levels depend on infants\u27 gestational rather than PMA

Fluorescent Protein Biosensor for Use in Parkinson\u27s Research

Purinergic signaling is a type of extracellular communication that occurs between cells, mediated by adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine. In Parkinson’s Disease, purinergic signaling is disrupted, which contributes to neurodegeneration. In order to monitor this change in cell-to-cell signaling, there is a need for the development of a fluorescent protein (FP) biosensor to study the changes in the concentration of the signaling molecule ATP and its decomposition bioproduct ADP. This summer a genetically encoded ADP sensor that measures changes in ADP concentration was developed. This sensor utilizes Forster Resonance Energy Transfer (FRET) which is a sensing technique that is based on the energy transfer from a donor FP to an acceptor FP. Since this transfer is distance dependent, a change in the sensing domain allows for detection of ADP concentration through changes in fluorescence emission. To develop this FRET based sensor, we are utilizing a cyan-yellow FP pair, as well as a non-fluorescent protein that binds to ADP. Using traditional cloning methods, a small library of ADP sensors from five different versions of both the cyan and yellow proteins was created. This library was screened in E. coli cultures using a method developed to optimize an ATP-sensor. The cloning for this sensor has been confirmed and the library is being tested for sensors responsive to changing concentrations of ADP. With confirmation of a responsive sensor, this sensor design will be validated, allowing for further optimization of this biosensor for the study of purinergic signaling and neurodegeneration

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference