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Tissue inhibitor of metalloproteinases 2 (TIMP2) is produced peripherally, crosses the blood-brain barrier, and improves synaptic plasticity and hippocampal-dependent cognition in aged mice; however, the role of TIMP2 in human cognitive aging is unclear. We examined associations of circulating TIMP2 levels in blood with a known plasticity-inducing behavior, physical activity, and cognitive functioning among older adults along the Alzheimer’s disease continuum.
Participants and Methods:
Participants included 84 community-dwelling older adults (meanage = 78.8; 57% female; 82% cognitively normal; 14% MCI; 4% mild dementia; 35% PET Aß+) enrolled in the UC San Francisco Memory and Aging Center. All participants completed 30 days of observational FitbitTM monitoring to quantify physical activity (average daily steps), as well as a comprehensive in-person visit including blood draw (proteins assayed on SOMAscan platform), [18F]AV-45 positron emission tomography (PET) to quantify brain beta-amyloid (centiloids), and neuropsychological assessment. Composite cognitive z-scores were calculated for memory (California Verbal Learning Test-II [CVLT-II] and Benson Figure Recall), semantic processing (animal fluency and Boston Naming Test), and executive functioning (digits backwards span, Stroop inhibition, modified trail making test, lexical fluency, and design fluency). Multiple linear regression examined TIMP2 as a function of physical activity, covarying for age and PET centiloids. Additional regression models separately examined cognitive z-scores as a function of TIMP2, covarying for age, sex, education, PET centiloids, and body mass index (BMI).
Results:
TIMP2 was not significantly correlated with age, sex, education, or PET centiloids (ps > 0.05); however, TIMP2 was negatively correlated with BMI (r = -0.23, p = 0.036). Greater average daily steps related to higher levels of TIMP2 (b = 0.30, 95%CI = 0.04-0.55, p = 0.022). TIMP2 also related to better semantic processing (b = 0.28, 95%CI = 0.04-0.51, p = 0.021) and executive functioning (b = 0.26, 95%CI = 0.03-0.49, p = 0.028). TIMP2 did not significantly relate to memory (p > 0.05).
Conclusions:
Greater physical activity was associated with higher concentrations of blood factor TIMP2, which in turn related to better cognitive functioning independent of Alzheimer’s disease pathology burden. These results support previous mouse models by broadly replicating relationships between TIMP2 and cognition in humans, while also uniquely demonstrating an association between TIMP2 and physical activity, a modifiable protective factor in both typical and diseased cognitive aging. Our domain-specific results, however, suggest that benefits of TIMP2 in humans may involve a broader neuroanatomical network than the hippocampal-specific effects previously shown in mice. Although exact mechanisms of TIMP2 need further examination, TIMP2 is known to be enriched in human umbilical cord plasma, has been shown to be involved in cell-growth promoting activities, and may relate to increased neural plasticity in older age. Further examination of TIMP2 and other novel blood-based proteins as potential therapeutic targets for improved cognitive aging, including in the presence of Alzheimer’s disease, is warranted.
In studies of Holocaust representation and memory, scholars of literature and culture traditionally have focused on particular national contexts. At the same time, recent work has brought the Holocaust into the arena of the transnational, leading to a crossroads between localized and global understandings of Holocaust memory. Further complicating the issue are generational shifts that occur with the passage of time, and which render memory and representations of the Holocaust ever more mediated, commodified, and departicularized. Nowhere is the inquiry into Holocaust memory more fraught or potentially more productive than in German Studies, where scholars have struggled to address German guilt and responsibility while doing justice to the global impact of the Holocaust, and are increasingly facing the challenge of engaging with the broader, interdisciplinary, transnational field. Persistent Legacy connects the present, critical scholarly moment with this long disciplinary tradition, probing the relationship between German Studies and Holocaust Studies today. Fifteen prominent scholars explore how German Studies engages with Holocaust memory and representation, pursuingcritical questions concerning the borders between the two fields and how they are impacted by emerging scholarly methods, new areas of inquiry, and the changing place of Holocaust memory in contemporary Germany.
Contributors: David Bathrick, Stephan Braese, William Collins Donahue, Tobias Ebbrecht-Hartmann, Katja Garloff, Andreas Huyssen, Irene Kacandes, Jennifer M. Kapczynski, Sven Kramer, Erin McGlothlin, Leslie Morris, Brad Prager, Karen Remmler, Michael D. Richardson, Liliane Weissberg.
Erin McGlothlin and Jennifer M. Kapczynski are both Associate Professors in the Department of Germanic Languages and Literatures at Washington University in St. Louis.
Single-walled carbon nanotubes (SWNTs) have exceptional mechanical and functional properties. Many researchers consider SWNTs as the most promising reinforcement for realizing the optimal structural and multifunctional potential of the next generation of high performance nanocomposites. However, due to poor dispersion, weak interfacial bonding and deficient tube orientation, current nanotube-based nanocomposites fail to realize their anticipated properties. A new approach was developed by the authors to use preformed nanotube tube networks (called buckypapers) and a resin infiltration method for producing bulk polymeric nanocomposites with controlled nanostructure and high tube loading. Desired tube alignment in nanocomposites can be achieved by using magnetically aligned carbon nanotube buckypapers, in which SWNTs will tend to align along the direction of applied magnetic field. The mechanical properties of the resultant nanocomposites have been tested. The storage modulus of the magnetically aligned nanocomposites is as high as 47 GPa, which is one of the highest reported values of nanotube-reinforced composites.
In this research, we investigated the influences of tube dispersion, loading and orientation on the mechanical properties of SWNT-reinforced composites. Random and aligned discontinuous reinforcement models of composites were applied to predict the tensile moduli of both individually dispersed SWNT-based and SWNT rope-based nanocomposites. The nanostructural parameters used in the calculation models were determined based on our experimental observations. Comparisons between theoretical estimates and experimental results have shown that the formation of SWNT ropes in the composites has a significant influence on the mechanical properties. The experimental results of the both random and aligned SWNT rope composites are in good agreement with the theoretical predictions.
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