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Activation of glycogen synthase kinase-3 (GSK-3) can cause memory deficits as seen in Alzheimer's disease, the most common age-associated dementia, but the mechanism is not understood. Here, we found that activation of GSK-3 by wortmannin or transient overexpression of wild-type GSK-3beta could suppress the induction of long-term potentiation (LTP) in rat(More)
Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer's disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at(More)
The integral equation (IE) method is commonly used to model time-harmonic electromagnetic (EM) phenomena. One of the major challenges in its application arises in the solution of the resulting ill-conditioned matrix equations. Here, we introduce a new domain decomposition (DD) based iterative method for the IE solution of time-harmonic electromagnetic(More)
OBJECTIVE To evaluate the effects of positive end-expiratory pressure (PEEP) on central venous pressure (CVP) and common iliac venous pressure (CIVP), the relationship between CVP and CIVP, in order to analyze the correlation between CVP or CIVP and airway pressure in patients during mechanical ventilation. METHODS Twenty mechanically ventilated adult(More)
Hyperphosphorylated tau is the major protein subunit of neurofibrillary tangles in Alzheimer's disease (AD) and related tauopathies. It is not understood, however, why the neurofibrillary tangle-containing neurons seen in the AD brains do not die of apoptosis but rather degeneration even though they are constantly awash in a proapoptotic environment. Here,(More)
Severe combined immunodeficiencies (SCID) are a group of rare inherited disorders with profound defects in T cell and B cell immunity. From 2005 to 2010, our unit performed testing for IL2RG, JAK3, IL7R, RAG1, RAG2, DCLRE1C, LIG4, AK2, and ZAP70 mutations in 42 Chinese and Southeast Asian infants with SCID adopting a candidate gene approach, based on(More)
Most patients with Alzheimer's disease (AD) present decreased levels of melatonin, a day-night rhythm-related hormone. To investigate the role of melatonin deficiency in AD, we used constant illumination to interrupt melatonin metabolism and measured some of the AD-like alterations in rats. Concomitant with decreased serum melatonin, the rats developed(More)
Hyperphosphorylated tau is the major component of neurofibrillary tangles in Alzheimer disease (AD), and the tangle distribution largely overlaps with zinc-containing glutamatergic neurons, suggesting that zinc released in synaptic terminals may play a role in tau phosphorylation. To explore this possibility, we treated cultured hippocampal slices or(More)
Acetylcholine is an important excitatory neurotransmitter, which plays a crucial role in synaptic transmission. The level of acetylcholine is decreased in the early stages of Alzheimer disease (AD), the most common neurodegenerative disease. Therefore, measurement of acetylcholine in the brain may help the clinical diagnosis of AD. However, the methods used(More)
Derivatives of 1-(4-amino-phenyl)-pyrrolidin-3-yl-amine and 6-(3-amino-pyrrolidin-1-yl)-pyridin-3-yl-amine were identified as potent and functionally active MCH-R1 antagonists. One compound with Ki = 2.3 nM demonstrated good oral bioavailability (32%) and in vivo efficacy in rats.