Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression via ERK pathway in mouse NIH-3T3 fibroblasts

Intact osteoactivin, a novel type I membrane glycoprotein, were shed at a dibasic motif in the juxtamembrane region in C2C12 myoblasts. Extracellular fragments were secreted into the culture media by a putative metalloprotease. Extracellular fragments of osteoactivin, but not control protein, induced matrix metalloprotease-3 (MMP-3) expression in NIH-3T3 fibroblasts. Epidermal growth factor (ERK) kinase inhibitors inhibited the osteoactivin-mediated MMP-3 expression, whereas the extracellular fragment of osteoactivin activated ERK1/2 and p38 in the mitogen-activated protein kinase pathway. Our results suggest that the extracellular fragments of osteoactivin produced by shedding act as a growth factor to induce MMP-3 expression via the ERK pathway in fibroblasts.     

Polysomnographic characteristics and predictors of positional obstructive sleep apnea in Japanese elderly

Sleep and Biological Rhythms - Sleep problems and obstructive sleep apnea (OSA) increase with age and disturb life in old age. Positional therapy is one option to treat OSA, but the differences in...     

Comparison Study of Allelochemicals and Bispyribac-Sodium on the Germination and Growth Response of Echinochloa crus-galli L.

The phytotoxic effects of two allelochemicals (trans-cinnamic acid and syringaldehyde) at different concentrations (1000, 100, 10, and 1 µM) on seed germination, seedling growth, and physiological and biochemical changes of Echinochloa crus-galli L. were tested by comparison to a commercial herbicide ‘Nominee’ (that is, 100 g/L bispyribac-sodium). trans-Cinnamic acid and the herbicide inhibited seed germination completely at 100 µM, whereas for syringaldehyde, complete inhibition required 1000 µM. However, with 100 µM syringaldehyde, the seed germination of the test species was 53% of the control. Allelochemicals and the herbicide delayed seed germination and significantly affected the speed of germination index (S), speed of cumulative germination index (AS), and coefficient of germination rate (CRG). The roots were more affected when nutrients were not added to the growth bioassay. In general, with the increasing concentration of allelochemicals from 100 to 1000 µM, the inhibitory effects increased. Via microscopy analysis, we found leaf blade wilting and necrosis at concentrations above 100 µM in allelochemical-treated plants. Roots of E. crus-galli treated with 1000 µM allelochemicals had black points on root nodes but had no root hairs. The anatomy of roots treated with allelochemicals (1000 µM) showed contraction or reduction of root pith cells as well as fewer and larger vacuoles compared to the control. The allelochemicals also showed remarkable effects on seedling growth, SPAD index, chlorophyll content, and free proline content in a pot culture bioassay, indicating that trans-cinnamic acid and syringaldehyde are potent inhibitors of E. crus-galli growth and can be developed as herbicides for future weed management strategies.

     

Delayed sleep/wake rhythm and excessive daytime sleepiness correlate with decreased daytime brain activity during cognitive task in university students

Insufficient sleep and irregular sleep/wake rhythm are common problems among university students. We investigated the effect of sleep/wake rhythm and excessive daytime sleepiness (EDS) on the cortical oxygenation as measured by near-infrared spectroscopy (NIRS) and cognitive performance in university students. Peak- and integral values by a word fluency task were measured with NIRS. EDS was evaluated by the Epworth sleepiness scale (ESS), and performance function was evaluated using N-back task. Peak cerebral oxygenation was significantly correlated with ESS, bedtime, wake-up time, and median time of sleep. Accuracy on 2-back task was significantly correlated with integral value. Peak- and integral values were significantly lower, and bedtime and median time of sleep were significantly delayed in the EDS group than in the non-EDS group. EDS accompanied by delayed sleep/wake rhythm and short sleep duration may play an important role in decreasing daytime brain activity and cognitive performance.     

Inhibition of human T-lymphocyte activation by macrolide antibiotic, roxithromycin.

Effects of macrolide antibiotic, roxithromycin (RXM) on human lymphocytes in culture were studied. The drug showed a dose-dependent inhibition of 3H-thymidine and 35S-methionine uptake responding to T cell mitogens and purified protein derivative of tuberculin (PPD). Activation by PPD, as assessed by 3H-thymidine uptake, was more sensitive to inhibition than the response to T cell mitogens. The drug produced a loss of blasts when added soon after transformation commenced. Immunosuppressive effects of RXM were further characterized by using four different types of metabolized RXM, RU 28111, RU 39001, RU 44981 and RU 45179. The most potent inhibitor of lymphocyte transformation was RU 45179, followed by RU 44981, RU 39001 and RU 28111 have little activity.     

Selective secretion of free glycine,a neutralizer against a plant defense chemical,in the digestive juice of the privet moth larvae

The larva of the privet moth, Brahmaea wallichii (Brahmaeidae) is a specialist feeder of the privet tree, Ligustrum obtusifolium (Oleaceae). A very high concentration (50 mM or 0.4%) of free glycine, found in the digestive juice of the larvae, works as a neutralizer against the very strong protein-denaturing activity of privet leaves that is caused by oleuropein, an iridoid that functions in chemical defense. Concentration of free glycine was high in the anterior region of the midgut lumen and low in the posterior region. To examine if some glycine-specific secretion mechanism exists, injection experiments were performed using (15)N-labeled amino acids. When 13 &mgr;mol (1 mg) of (15)N-glycine was injected into hemolymph of fifth instar larvae of B. wallichii, a high concentration of (15)N (5 mM or 75 &mgr;g/g midgut content) was detected in the anterior parts of the midgut lumen 1 h after injection. (15)N-NMR data indicated at least 60% of the (15)N found in midgut lumen existed as (15)N-glycine. Approximately, 25% of the injected (15)N-glycine was estimated to have moved from the hemolymph to the midgut lumen. In contrast, no (15)N was detected in the midgut lumen when 13 &mgr;mol of (15)N-labeled alanine, lysine and glutamate were injected into hemolymph. Glycine was the only amino acid whose concentration was higher in the midgut lumen (50 mM) than in the hemolymph (22 mM). These data suggest the existence of some active and glycine-specific secretory mechanism in the midgut of B. wallichii.     

Crystal structure of Escherichia coli methionyl-tRNA synthetase highlights species-specific features

The 3D structure of monomeric C-truncated Escherichia coli methionyl-tRNA synthetase, a class 1 aminoacyl-tRNA synthetase, has been solved at 2.0 A resolution. Remarkably, the polypeptide connecting the two halves of the Rossmann fold exposes two identical knuckles related by a 2-fold axis but with zinc in the distal knuckle only. Examination of available MetRS orthologs reveals four classes according to the number and zinc content of the putative knuckles. Extreme cases are exemplified by the MetRS of eucaryotic or archaeal origin, where two knuckles and two metal ions are expected, and by the mitochondrial enzymes, which are predicted to have one knuckle without metal ion.     

Cellular expression of murine Ym1 and Ym2, chitinase family proteins,as revealed by in situ hybridization and immunohistochemistry

Ym is one of the chitinase family proteins, which are widely distributed in mammalian bodies and can bind glycosaminoglycans such as heparin/heparan sulfate. Ym1 is a macrophage protein produced in parasitic infections, while its isoform, Ym2, is upregulated in lung under allergic conditions. In the present study, we revealed the distinct cellular expression of Ym1 and Ym2 in normal mice by in situ hybridization and immunohistochemistry. Ym1 was principally expressed in the lung, spleen, and bone marrow, while Ym2 was found in the stomach. Ym1-expressing cells in the lung were alveolar macrophages, and the immunoreactivity for Ym1 was localized in rough endoplasmic reticulum. In the spleen, Ym1-expressing cells gathered in the red pulp and were electron microscopically identified as immature neutrophils. In the bone marrow, immature neutrophils were intensely immunoreactive, but lost this immunoreactivity with maturation. Moreover, needle-shaped crystals in the cytoplasm of macrophages, which formed erythroblastic islands, also showed intense Ym1 immunoreactivity. Ym2 expression was restricted to the stratified squamous epithelium in the junctional region between forestomach and glandular stomach. The function of Ym1 and Ym2 is still unclear; however, the distinct cellular localization under normal conditions suggests their important roles in hematopoiesis, tissue remodeling, or immune responses as an endogenous lectin.     

Synthesis and mitochondrial complex I inhibition of dihydroxy-cohibin A, non-THF annonaceous acetogenin analogue

To elucidate the inhibitory action of acetogenins, we synthesized an acetogenin derivative which possesses tetraol in place of the tetrahydrofuran ring and examined its inhibitory activity against bovine heart mitochondrial complex I. Our results indicate that these hydroxy groups are an essential structural factor though it is not effective as bis-THF hydroxy groups combination.