546,247 research outputs found
Still standing, still here, still dancing.
A personal narrative is presented which explores the author's experiences on teaching-learning process and her insights on language, culture and learning
LRR Voices: Health & Safety for Unorganized, Immigrant Workers
Pam Tau Lee is Labor Coordinator at the Labor Occupational Health Program at the University of California, Berkeley, and serves on the boards of the National Toxic Campaign Fund, National People of Color Environmental Summit, and the Chinese Progressive Association, She recently returned from Slovakia where she collaborated with environmentalists and worker representatives in setting up a participatory approach to health and safety research. LRR asked Lee to comment on the crucial role labor can play in the area of health and safety for unorganized, immigrant workers
Is there any nontrivial compact generalized shift operator on Hilbert spaces?
In the following text for cardinal number , and self--map
we show the generalized shift operator
(where
for ) if and only if
is bounded and in this case
is
continuous, consequently
is a
compact operator if and only if is finite.Comment: 5 page
In vivo microdialysis reveals age-dependent decrease of brain interstitial fluid tau levels in P301S human tau transgenic mice
Although tau is a cytoplasmic protein, it is also found in brain extracellular fluids, e.g., CSF. Recent findings suggest that aggregated tau can be transferred between cells and extracellular tau aggregates might mediate spread of tau pathology. Despite these data, details of whether tau is normally released into the brain interstitial fluid (ISF), its concentration in ISF in relation to CSF, and whether ISF tau is influenced by its aggregation are unknown. To address these issues, we developed a microdialysis technique to analyze monomeric ISF tau levels within the hippocampus of awake, freely moving mice. We detected tau in ISF of wild-type mice, suggesting that tau is released in the absence of neurodegeneration. ISF tau was significantly higher than CSF tau and their concentrations were not significantly correlated. Using P301S human tau transgenic mice (P301S tg mice), we found that ISF tau is fivefold higher than endogenous murine tau, consistent with its elevated levels of expression. However, following the onset of tau aggregation, monomeric ISF tau decreased markedly. Biochemical analysis demonstrated that soluble tau in brain homogenates decreased along with the deposition of insoluble tau. Tau fibrils injected into the hippocampus decreased ISF tau, suggesting that extracellular tau is in equilibrium with extracellular or intracellular tau aggregates. This technique should facilitate further studies of tau secretion, spread of tau pathology, the effects of different disease states on ISF tau, and the efficacy of experimental treatments
Targeting tauopathy with engineered tau-degrading intrabodies
BACKGROUND: The accumulation of pathological tau is the main component of neurofibrillary tangles and other tau aggregates in several neurodegenerative diseases, referred to as tauopathies. Recently, immunotherapeutic approaches targeting tau have been demonstrated to be beneficial in decreasing tauopathy in animal models. We previously found that passive immunotherapy with anti-tau antibody to human tau or expression of an anti-tau secreted single-chain variable fragment (scFv) in the central nervous system of a mouse model of tauopathy decreased but did not remove all tau-associated pathology. Although these and other studies demonstrate that conventional immunotherapeutic approaches targeting tau can influence tau pathogenesis, the majority of pathological tau remains in the cytosol of cells, not typically accessible to an extracellular antibody. Therefore, we reasoned targeting intracellular tau might be more efficacious in preventing or decreasing tauopathy.
METHODS: By utilizing our anti-tau scFv, we generated anti-tau intrabodies for the expression in the cytosol of neurons. To enhance the degradation capacity of conventional intrabodies, we engineered chimeric anti-tau intrabodies fused to ubiquitin harboring distinct mutations that shuttle intracellular tau for either the proteasome or lysosomal mediated degradation. To evaluate the efficacy in delaying or eliminating tauopathy, we expressed our tau degrading intrabodies or controls in human tau transgenic mice by adeno-associated virus prior to overt tau pathology and after tau deposition.
RESULTS: Our results demonstrate, the expression of chimeric anti-tau intrabodies significantly reduce tau protein levels in primary neuronal cultures expression human tau relative to a non-modified anti-tau intrabody. We found the expression of engineered tau-degrading intrabodies destined for proteasomal-mediated degradation are more effective in delaying or eliminating tauopathy than a conventional intrabody in aged human tau transgenic mice.
CONCLUSION: This study, harnesses the strength of intrabodies that are amendable for targeting specific domains or modifications with the cell-intrinsic mechanisms that regulate protein degradation providing a new immunotherapeutic approach with potentially improved efficacy
Measurement of the lepton polarization and in the decay with one-prong hadronic decays at Belle
With the full data sample of pairs recorded by
the Belle detector at the KEKB electron-positron collider, the decay is studied with the hadronic
decays and . The polarization in two-body hadronic
decays is measured, as well as the ratio of the branching fractions , where
denotes an electron or a muon. Our results, and , are consistent with the theoretical
predictions of the Standard Model. The polarization values of are excluded at the 90\% confidence level.Comment: 17 pages, 11 figures, submitted to Physical Review
- …