Identifying characteristics of frailty in female mice using a phenotype assessment tool

Preclinical studies are important in identifying the underlying mechanisms contributing to frailty. Frailty studies have mainly focused on male rodents with little directed at female rodents. Therefore, the purposes of this study were to identify the onset and prevalence of frailty across the life span in female mice, and to determine if frailty predicts mortality. Female C57BL/6 (n = 27) mice starting at 17 months of age were assessed across the life span using a frailty phenotype, which included body weight, walking speed, strength, endurance, and physical activity. The onset of frailty occurred at approximately 17 months (1/27 mice), with the prevalence of frailty increasing thereafter. At 17 months, 11.1% of the mice were pre-frail and by 26 months peaked at 36.9%. The percentage of frail mice progressively increased up to 66.7% at 32 months. Non-frail mice lived to 29 months whereas frail/pre-frail mice lived only to 26 months (p = .04). In closing, using a mouse frailty phenotype, we are able to identify that the prevalence of frailty in female mice increases across the life span and accurately predicts mortality. Together, this frailty phenotype has the potential to yield information about the underlying mechanisms contributing to frailty.T32 AG029796 - NIA NIH HHSPublished versio

Sex-specific components of frailty in C57BL/6 mice.

Many age-related biochemical, physiological and behavioral changes are known to be sex-specific. However, how sex influences frailty status and mortality risk in frail rodents has yet to be established. The purpose of this study was therefore to characterize sex differences in frail mice across the lifespan. Male (n=29) and female (n=27) mice starting at 17 months of age were assessed using a frailty phenotype adjusted according to sex, which included body weight, walking speed, strength, endurance and physical activity. Regardless of sex, frail mice were phenotypically dysfunctional compared to age-matched non-frail mice, while non-frail females generally possessed a higher body fat percentage and were more physically active than non-frail males (p≤0.05). The prevalence of frailty was greater in female mice at 26 months of age (p=0.05), but if normalized to mean lifespan, no sex differences remained. No differences were detected in the rate of death or mean lifespan between frail male and female mice (p≥0.12). In closing, these data indicate that sexual differences exist in aging C57BL/6 mice and if the frailty criteria are adjusted according to sex, the prevalence of frailty increases across age with frail mice dying early in life, regardless of sex.T32 AG029796 - NIA NIH HHS; T32 AR007612 - NIAMS NIH HHSPublished versio

Three-dimensional time dependent computation of turbulent flow

The three-dimensional, primitive equations of motion are solved numerically for the case of isotropic box turbulence and the distortion of homogeneous turbulence by irrotational plane strain at large Reynolds numbers. A Gaussian filter is applied to governing equations to define the large scale field. This gives rise to additional second order computed scale stresses (Leonard stresses). The residual stresses are simulated through an eddy viscosity. Uniform grids are used, with a fourth order differencing scheme in space and a second order Adams-Bashforth predictor for explicit time stepping. The results are compared to the experiments and statistical information extracted from the computer generated data

Downhill exercise alters immunoproteasome content in mouse skeletal muscle

Content of the immunoproteasome, the inducible form of the standard proteasome, increases in atrophic muscle suggesting it may be associated with skeletal muscle remodeling. However, it remains unknown if the immunoproteasome responds to stressful situations that do not promote large perturbations in skeletal muscle proteolysis. The purpose of this study was to determine how an acute bout of muscular stress influences immunoproteasome content. To accomplish this, wildtype (WT) and immunoproteasome knockout lmp7-/-/mecl1-/-(L7M1) mice were run downhill on a motorized treadmill. Soleus muscles were excised 1 and 3 days post-exercise and compared to unexercised muscle(control). Ex vivophysiology, histology and biochemical analyses were used to assess the effects of immunoproteasome knockout and unaccustomed exercise. Besides L7M1 muscle being LMP7/MECL1deficient, no other major biochemical, histological or functional differences were observed between the control muscles. In both strains, the downhill run shifted the force-frequency curve to the right and reduced twitch force, however did not alter tetanic force or inflammatory markers. In the days post-exercise, several of the proteasome 's catalytic subunits were upregulated. Specifically, WT muscle increased LMP7 while L7M1 muscle instead increased ≤ 5. These findings indicate that running mice downhill results in subtle contractile characteristics that correspond to skeletal muscle injury, yet does not appear to induce a significant inflammatory response. Interestingly, this minor stress activated the production of specific immunoproteasome subunits; that if knocked out, were replaced by components of the standard proteasome. These data suggest that the immunoproteasome may be involved in maintaining cellular homeostasis.This study was supported by the Elaine and Robert Larson Endowed Vision Research Chair (to DAF), the National Institutes of Health/National Institute of Aging (T32-AG29796 to CWB), an anonymous benefactor for Macular Degeneration Research, the Lindsay Family Foundation and an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology and Visual Neurosciences. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. (Elaine and Robert Larson Endowed Vision Research Chair; T32-AG29796 - National Institutes of Health/National Institute of Aging; Lindsay Family Foundation; Research to Prevent Blindness)Accepted manuscrip

Japanese foreign direct investment : recent trends, determinants, and prospects

In the late 1980s, Japan became the biggest source of foreign direct investment (FDI) in the world. The main beneficiaries of the rapid increase in investment flows were industrial countries, but the developing world (especially East Asia and Latin America) also received substantial inflows. In East Asia, the newly industrial economies (NIEs) of Hong Kong, Republic of Korea, Singapore, and Taiwan (China) were, at first, production bases for Japanese manufacturing in the 1970s and early 1980s. But in the late 1980s, these countries became new, expanding consumer markets, attracting huge Japanese investments in the tertiary (service) sector, while investments in manufacturing shrank rapidly because of rising labor costs. The Association of Southeast Nations (ASEAN) and China became Japan's new production base. In Latin America (mostly small Caribbean countries) Japan's focus is almost exclusively on tax havens. Globally, Japan's investments in the secondary (manufacturing) and service sectors of the major Latin American nations are only marginal. Japanese investment flows declined drastically after 1989, mostly because of the depressed global and domestic economy, after rapid asset price deflation in Japan. Hardest hit by the decline were the United States and Europe. Japanese FDI flows to developing countries also declined, but less. The biggest losers were the NIEs and the Caribbean tax havens. The biggest losers were the NIEs and the Caribbean tax havens. Japanese investments continued to grow in other Latin American countries and, even more, in the ASEAN and China. Japanese investors sharply reduced tertiary sector investments, primarily geared to maintaining or expanding markets. Investments in the secondary sector, making use of low-cost production, continued to expand. This trend is expected to continue in the near future, with FDI flows declining further, albeit more slowly. Low-wage production countries such as China and Indonesia will attract an increasing share. Investment to expand markets in the industrial countries and the NIEs are likely to decline. But medium-term prospects for Japanese FDI in developing countries are brighter, as economic recovery and continuing current account surpluses in Japan will lead to a resumption of active foreign investment by Japanese multinational corporations.Foreign Direct Investment,Environmental Economics&Policies,International Terrorism&Counterterrorism,Economic Theory&Research,Trade and Regional Integration

Political Involvement in “Mobilized” Society: The Interactive Relationships Among Mobile Communication, Network Characteristics, and Political Participation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89468/1/j.1460-2466.2011.01601.x.pd

Mobile Communication and Civil Society: Linking Patterns and Places of Use to Engagement with Others in Public

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91226/1/j.1468-2958.2010.01399.x.pd

Growth, Condition, and Trophic Relations of Stocked Trout in Southern Appalachian Mountain Streams

Stream trout fisheries are among the most popular and valuable in the United States, but many are dependent on hatcheries to sustain fishing and harvest. Thus, understanding the ecology of hatchery‐reared trout stocked in natural environments is fundamental to management. We evaluated the growth, condition, and trophic relations of Brook Trout Salvelinus fontinalis, Brown Trout Salmo trutta, and Rainbow Trout Oncorhynchus mykiss that were stocked in southern Appalachian Mountain streams in western North Carolina. Stocked and wild (naturalized) trout were sampled over time (monthly; September 2012–June 2013) to compare condition and diet composition and to evaluate temporal dynamics of trophic position with stable isotope analysis. Relative weights (Wr) of stocked trout were inversely associated with their stream residence time but were consistently higher than those of wild trout. Weight loss of harvested stocked trout was similar among species and sizes, but fish stocked earlier lost more weight. Overall, 40% of 141 stomachs from stocked trout were empty compared to 15% of wild trout stomachs (N = 26). We identified a much higher rate of piscivory in wild trout (18 times that of stocked trout), and wild trout were 4.3 times more likely to consume gastropods relative to stocked trout. Hatchery‐reared trout were isotopically similar to co‐occurring wild fish for both δ13C and δ15N values but were less variable than wild trout. Differences in sulfur isotope ratios (δ34S) between wild and hatchery‐reared trout indicated that the diets of wild fish were enriched in δ34S relative to the diets of hatchery‐reared fish. Although hatcheryreared trout consumed prey items similar to those of wild fish, differences in consumption or behavior (e.g., reduced feeding) may have resulted in lower condition and negative growth. These findings provide critical insight on the trophic dynamics of stocked trout and may assist in developing and enhancing stream trout fisheries

Invariances and Equations of Motion in Double Field Theory

We investigate the full set of equations of motion in double field theory and discuss their O(D,D) symmetry and gauge transformation properties. We obtain a Ricci-like tensor, its associated Bianchi identities, and relate our results to those with a generalized metric formulation.Comment: 24 page