Beta-angonists modulate ACh-inhibition of a K current in intestinal smooth muscle cells.

ACh causes a long-lasting inhibition of STOCs via G proteins in intestinal smooth muscle cells. We examined the effects of isoproterenol (Iso) on the ACh-induced inhibition of STOCs in isolated ileal smooth muscle cells using the G omega-seal whole cell clamp technique. In control, ACh (1 microM) completely suppressed STOCs, which did not desensitize over a period lasting 20 minutes. When Iso (10 microM) was added to the bath in the presence of ACh, the ACh-induced inhibition of STOCs was gradually removed. This effect of Iso was prevented by propranolol (10 microM). Application of Db-cAMP (500 microM) mimicked the Iso effects. Intracellulary applied GTP-gamma S (100 microM) gradually suppressed STOCs in the absence of ACh, which could not be removed by either Iso or Db-cAMP. These results suggest that beta-adrenergic stimulation causes a removal of the muscarinic inhibition of STOCs via a cAMP-dependent process.     

Multivariable analysis of serum 3,5,3'-L-triiodothyronine concentration in patients of diabetes mellitus by blood glucose level and body weight

Serum thyroid hormone concentrations, 1-thyroxine (T4), free T4 and 3,5,3'-l-triiodothyronine (T3) were measured in 213 patients of diabetes and analyzed their correlation with metabolic parameters, hyperglycemia and body weight. Haemoglobin A1 (HbA1) was used as an index of hyperglycemia. Body weight was expressed by relative body weight (body weight/standard weight). Among the thyroid hormones, only T3 had significant correlation with HbA1 and body weight (r = -0.476, P less than 0.01 and r = 0.369, P less than 0.01, respectively). Multivariable analysis of serum T3 by HbA1 and relative body weight gave the following regression equation. Serum T3 (ng/dl) = 108 + 0.362 x relative body weight (%) - 3.88 x HbA 1 (%). Though relative body weight had inverse correlation with HbA1, the contribution of the two metabolic parameters to the serum T3 was independent from each other. Our results confirm the previous reports that low T3 in diabetes correlates with severity of hyperglycemia and we report for the first time that serum T3 of diabetic patients has positive correlation with body weight, probably due to still available carbohydrate in spite of disturbances in the metabolism.     

Chemical composition of Streptococcus mutans cell walls and their susceptibility to Flavobacterium L-11 enzyme

The susceptibility to a cell wall lytic L-11 enzyme from Flavobacterium sp. and the quantitative and/or qualitative composition of the cell walls of some strains of cariogenic Streptococcus mutans and a non-cariogenic strain of Streptococcus mitis were determined. The purified cell walls of S. mutans strains HS-1 (serotype a), BHT (b), NCTC10449 (c), C67-1 (c), C67-25 (c), OMZ 176 (d), MT703 (e), MT557 (f), OMZ65 (g), and AHT (g), and S. mitis CHT contained glutamic acid, alanine, and lysine as well as muramic acid and glucosamine as a peptidoglycan component. Besides these amino acids, significant amounts of threonine were detected in strains HS-1, OMZ65, and AHT cell walls, and considerable amounts of aspartic acid and/or threonine as well as several other amino acids in OMZ176, OMZ65, and CHT cell walls. Rhamnose was a common special component of the cell walls of S. mutans strains BHT, NCTC10449, MT703, B2 (e), MT557, and AHT, and S. mitis CHT. An additional sugar component, glucose, was detected in the cell walls of all of these strains except BHT, and galactose was found in BHT, AHT, and CHT cell walls. Galactosamine was present in S. mitis CHT cell walls. Varying amounts of phosphorus were detected in the cell walls of all the strains examined. The cell walls of all these streptococcal strains except MT703, 6715, and AHT were susceptible to the lytic action of the L-11 enzyme to various extents. No consistent relationship was observed between the amino acid and sugar composition of these cell walls and their susceptibility to the L-11 enzyme. The chemical composition of these cell walls is discussed in terms of the serological classification of S. mutans.     

Chemical modification of neamine

The aminocyclitol antibiotic neamine has been modified by changing the configuration of one or two hydroxyl groups of the aminocyclitol moiety to elucidate the relationship between configuration and antimicrobial activity. 5-Epi-, 6-epi-, and 5,6-diepineamine have been prepared and their antimicrobial activity has been determined against several micro-organisms.     

Can biochemical traits bridge the gap between genomics and plant performance? A study in rice under drought

The possibility of introducing metabolic/biochemical phenotyping to complement genomics-based predictions in breeding pipelines has been considered for years. Here we examine to what extent and under what environmental conditions metabolic/biochemical traits can effectively contribute to understanding and predicting plant performance. In this study, multivariable statistical models based on flag leaf central metabolism and oxidative stress status were used to predict grain yield (GY) performance for 271 indica rice (Oryza sativa) accessions grown in the field under well-watered and reproductive stage drought conditions. The resulting models displayed significantly higher predictability than multivariable models based on genomic data for the prediction of GY under drought (Q² = 0.54–0.56 versus 0.35) and for stress-induced GY loss (Q² = 0.59–0.64 versus 0.03–0.06). Models based on the combined datasets showed predictabilities similar to metabolic/biochemical-based models alone. In contrast to genetic markers, models with enzyme activities and metabolite values also quantitatively integrated the effect of physiological differences such as plant height on GY. The models highlighted antioxidant enzymes of the ascorbate–glutathione cycle and a lipid oxidation stress marker as important predictors of rice GY stability under drought at the reproductive stage, and these stress-related variables were more predictive than leaf central metabolites. These findings provide evidence that metabolic/biochemical traits can integrate dynamic cellular and physiological responses to the environment and can help bridge the gap between the genome and the phenome of crops as predictors of GY performance under drought.

Biochemical traits outperform the explanatory power of genetic markers when used as variables in models for predicting yield performance in rice under drought stress.     

The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts

Plasmodium sporozoites that are transmitted by blood-feeding female Anopheles mosquitoes invade hepatocytes for an initial round of intracellular replication, leading to the release of merozoites that invade and multiply within red blood cells. Sporozoites and merozoites share a number of proteins that are expressed by both stages, including the Apical Membrane Antigen 1 (AMA1) and the Rhoptry Neck Proteins (RONs). Although AMA1 and RONs are essential for merozoite invasion of erythrocytes during asexual blood stage replication of the parasite, their function in sporozoites was still unclear. Here we show that AMA1 interacts with RONs in mature sporozoites. By using DiCre-mediated conditional gene deletion in P. berghei, we demonstrate that loss of AMA1, RON2 or RON4 in sporozoites impairs colonization of the mosquito salivary glands and invasion of mammalian hepatocytes, without affecting transcellular parasite migration. Three-dimensional electron microscopy data showed that sporozoites enter salivary gland cells through a ring-like structure and by forming a transient vacuole. The absence of a functional AMA1-RON complex led to an altered morphology of the entry junction, associated with epithelial cell damage. Our data establish that AMA1 and RONs facilitate host cell invasion across Plasmodium invasive stages, and suggest that sporozoites use the AMA1-RON complex to efficiently and safely enter the mosquito salivary glands to ensure successful parasite transmission. These results open up the possibility of targeting the AMA1-RON complex for transmission-blocking antimalarial strategies.     

Stimulatory effects of LH on release of melatonin and activities of its synthesizing enzymes NAT and HIOMT in organ-cultured pineal glands of female rats.

The pineal hormone melatonin (N-acetyl-5-methoxytryptamine) exerts antigonadotropic effects in some mammalian species. To evaluate the effect of luteinizing hormone (LH) on melatonin release and its synthesizing enzyme activities in pineal glands, pineals of adult female rats undergoing diestrus were organ-cultured in a medium containing 10(-12), 10(-10) or 10(-8) M LH for 6 h. Melatonin release increased significantly in pineals cultured with 10(-12) and 10(-10) M LH, as compared to control values. Similarly, the activity of arylalkylamine N-acetyltransferase (NAT), the key regulatory enzyme in melatonin biosynthesis, was significantly higher in pineals cultured with 10(-12) and 10(-10) M LH for 6 h, while LH at 10(-8) M had no effect. Although LH at 10(-10) M increased pineal hydroxyindole-O-methyltransferase (HIOMT) activity, which catalyzes the final step of melatonin biosynthesis, LH at 10(-12) and 10(-8) M had no effect. These results demonstrate that at relatively low physiological levels, LH stimulates pineal melatonin synthesis and release, mainly by increasing NAT activity.     

Internal brooding of clonal propagules by a sea anemone, Anthopleura sp.

Abstract. We investigated the seasonal prevalence of reproductive activities and of the development of brooded propagules in an intertidal sea anemone, Anthopleura sp., on the rocky shore of Mutsu Bay, in northern Japan. A monthly examination of anemones, by dissection and histological techniques, revealed no sign of gonad development, but did reveal that they produce and internally brood propagules throughout the year. Release of propagules was observed in the field. This anemone population appears to be entirely asexual and agametic, and may persist solely through clonal propagation.     

High-dose zolpidem abuse in a patient with insomnia comorbid with major depressive disorder

Sleep and Biological Rhythms - A 39-year-old married woman was referred to a psychiatry outpatient clinic for treatment of major depressive disorder (MDD). The dose of zolpidem she had been taking...