Tau/PTL-1 associates with kinesin-3 KIF1A/UNC-104 and affects the motor's motility characteristics in C. elegans neurons.

Tauopathies are neurodegenerative diseases based on pathological tau-aggregation including Alzheimer's disease, frontotemporal dementia (FTD) and Pick's disease. In general, cargo (e.g., ß-amyloid precursor protein, tau, neurofilaments) accumulation is a commonly observed phenomenon in degenerated neurons. Therefore, it is crucial to investigate the interaction between cargo, microtubule-binding proteins and molecular motors. We report the effect of tau/PTL-1 (protein with tau-like repeats) on the transport characteristics of the major axonal transporter kinesin-3 KIF1A/UNC-104 in the nervous system of Caenorhabditis elegans. Using confocal spinning disk time-lapse imaging we analyzed the motility of UNC-104::mRFP in ptl-1 knockout worms and found that predominantly retrograde moving characteristics are affected (rather than the motor's anterograde displacements). A similar motility pattern was observed for synaptobrevin-1-containing vesicles, a major cargo of UNC-104. Moreover, UNC-104 and PTL-1 colocalize and occasionally co-migrate. We further confirmed physical interactions between PTL-1 and UNC-104 in living animals using the bimolecular fluorescence complementation assay (BiFC) as well as in co-immunoprecipitation experiments. Though this study focuses on PTL-1/UNC-104 interactions, we extended our research on monitoring conventional kinesin-1 (UNC-116) as well as dynein motility pattern and found that in ptl-1 mutants retrograde displacements were also affected for UNC-116, while for dynein, interestingly, its anterograde movements were affected.

Dimethylthiourea pretreatment inhibits endotoxin-induced compound exocytosis in goblet cells and plasma leakage of rat small intestine.

Intravenous application of a high dose of endotoxin, also called lipopoly-saccharide (LPS), results in endotoxemia in animals, that induces production of cytokines and free radicals, systemic inflammation and mucin discharge from mucous tissues. The present study was to investigate (1) whether LPS application increased goblet cell secretion by compound exocytotic activity in mucosal villi and crypts of rat small intestine, and (2) whether hydroxyl radicals were involved in LPS-induced compound exocytosis in goblet cells and plasma leakage. Scanning electron microscopy showed that the numbers of goblet cells undergoing compound exocytosis (cavitated goblet cells) per mm(2) of ileal villus epithelium in rats 5 and 30 min after LPS (15 mg kg(-1)) were 693 +/- 196 (N = 6) and 547 +/- 213 (N = 6), respectively, which were 5.1 and 8.4 times (P < 0.05) the number of saline control. The percentage of villus cavitated goblet cell numbers, in both duodenum and ileum 5 min after LPS and in the ileum 30 min after LPS, increased significantly (P < 0.05). Pretreatment with dimethylthiourea (DMTU), a hydroxyl radical scavenger, decreased the number of cavitated goblet cells to saline control (P > 0.05). Morphometric analysis showed that the percentage of crypt epithelial area in the duodenum and ileum occupied by goblet cell mucin stores in the duodenum and ileum 30 min after LPS were 3.8 +/- 0.2% (N = 6) and 6.9 +/- 0.5 (N = 6), respectively reducing to one half the amount of control (P < 0.01). When DMTU was given prior to LPS the crypt goblet cell mucin stores and the amount of plasma leakage returned to the level of control. It is concluded that hydroxyl radicals were involved in the LPS-induced increase in compound exocytotic activity of goblet cells and the increase in plasma leakage during acute phases of inflammatory response in rat small intestine.

Immunomodulatory effect of Antrodia camphorata mycelia and culture filtrate.

AIM OF THE STUDY: Antrodia camphorata, a precious folkloric medicinal mushroom, has been used to treat tumorigenic diseases in Taiwan. This study was to investigate the innate immunity augmentation effects of different fractions prepared from hot water extracts of submerged cultured Antrodia camphorata (AC). MATERIALS AND METHODS: The cytokine induction potency of AC fraction in diluted peripheral blood culture was measured by ELISA. The effects of AC fraction on phagocytic activity and CD11b expression were measured by the ingestion of FITC-labeled Escherichia coli and by labeling with PE-labeled CD11b monoclonal antibody, respectively, using flow cytometry. The molecular mass of hot water-soluble polysaccharides and content of adenosine in AC fraction were determined by gel permeation chromatography (GPC) and HPLC, respectively. RESULTS: The mycelia fraction, Fr. M II, and culture filtrate fractions, Fr. E II and Fr. E III, showed the strongest TNF-alpha and IL-6 induction effect as a function of their concentration. These fractions (20mug/ml) also showed marked activity in enhancing phagocytosis in human polymorphonuclear neutrophils (PMN) and monocytes. In parallel, the expression of CD11b, an early marker of PMN activation, was also up-regulated dose-dependently. Composition analysis suggested that immunomodulatory effect of mycelia is mainly attributed to the 10-20kDa polysaccharides and adenosine. CONCLUSIONS: These results provide evidences that Antrodia camphorata can modulate innate immunity and may serve as an adjuvant for tumor treatment.

Novel Organic Phototransistor-Based Nonvolatile Memory Integrated with UV-Sensing/Green-Emissive Aggregation Enhanced Emission (AEE)-Active Aromatic Polyamide Electret Layer.

A novel aggregation enhanced emission (AEE)-active polyamide TPA-CN-TPE with a high photoluminesence characteristic was successfully synthesized by the direct polymerization of 4-cyanotriphenyl diamine (TPA-CN) and tetraphenylethene (TPE)-containing dicarboxylic acid. The obtained luminescent polyamide plays a significant role as the polymer electret layer in organic field-effect transistors (OFETs)-type memory. The strong green emission of TPA-CN-TPE under ultraviolet (UV) irradiation can be directly absorbed by the pentacene channel, displaying a light-induced programming and voltage-driven erasing organic phototransistor-based nonvolatile memory. Memory window can be effectively manipulated between the programming and erasing states by applying UV light illumination and electrical field, respectively. The photoinduced memory behavior can be maintained for over 104 s between these two states with an on/off ratio of 104, and the memory switching can be steadily operated for many cycles. With high photoresponsivity ( R) and photosensitivity ( S), this organic phototransistor integrated with AEE-active polyamide electret layer could serve as an excellent candidate for UV photodetectors in optical applications. For comparison, an AEE-inactive aromatic polyimide TPA-PIS electret with much weaker solid-state emission was also applied in the same OFETs device architecture, but this device did not show any UV-sensitive and UV-induced memory characteristics, which further confirmed the significance of the light-emitting capability of the electret layer.

What's Cooking? - Cognitive Training of Executive Function in the Elderly.

Executive function involves the efficient and adaptive engagement of the control processes of updating, shifting, and inhibition (Miyake, 2000) to guide behavior toward a goal. It is associated with decrements in many other cognitive functions due to aging (West, 1996; Raz, 2000) with itself particularly vulnerable to the effect of aging (Treitz et al., 2007). Cognitive training in the form of structural experience with executive coordination demands exhibited effective enhancement in the elderly (Hertzog et al., 2008). The current study was thus aimed at the development and evaluation of a training regime for executive function in the elderly. The breakfast cooking task of Craik and Bialystok (2006) was adapted into a multitasking training task in a session (pre-test vs. post-test) by group (control vs. training). In the training condition, participants constantly switched, updated, and planned in order to control the cooking of several foods and concurrently performed a table setting secondary task. Training gains were exhibited on task related measures. Transfer effect was selectively observed on the letter-number sequencing and digit symbol coding test. The cooking training produced short term increase in the efficiency of executive control processing. These effects were interpreted in terms of the process overlap between the training and the transfer tasks.

Immunomodulatory effect of exo-polysaccharides from submerged cultured Cordyceps sinensis: enhancement of cytokine synthesis, CD11b expression, and phagocytosis.

Cordyceps sinensis is widely used as a traditional medicine for treatment of a wide variety of diseases or to maintain health. The immunomodulatory activity of polysaccharides prepared from submerged cultured C. sinensis BCRC36421 was investigated in human peripheral blood. Results demonstrated that Fr. A (exo-polysaccharides, 0.025 approximately 0.1 mg/ml) induced the production of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and IL-10 dose-dependently. Fr. A, as low as 0.025 mg/ml, could significantly augment surface expression of CD11b in monocytes and polymorphonuclear neutrophils. Functional assay revealed that Fr. A (0.05 mg/ml) also elevated phagocytosis in monocytes and PMN. On the other hand, Fr. B (intracellular polysaccharides) only moderately induced TNF-alpha release, CD11b expression, and phagocytosis at the same concentrations. Our results indicate that the immunomodulatory components of submerged cultured C. sinensis mainly reside in the culture filtrate.

Statistical optimization of medium components for the production of Antrodia cinnamomea AC0623 in submerged cultures.

The nutritional medium requirement for biomass and triterpenoid production by Antrodia cinnamomea AC0623 strain was optimized. Box-Behnken was applied to optimize biomass and triterpenoid production. According to response surface methodology (RSM), the optimum concentrations of N-source were determined. The results indicate that when a submerged culture in shake flasks was operated at 28 degrees C, initial pH 5.5, and rotation speed 105 rpm, the biomass and triterpenoid content in dry basis could be increased to 3.20% (w/w) and 31.8 mg/g, respectively. The experiments were further scaled up to 100- and 700-l fermentors. Higher content of triterpenoids (63.0 mg/g) was obtained in 700-l fermentations by means of the control of cultural conditions and the modification of medium composition based on the RSM.