Analysis of the biosynthetic process of cellulose and curdlan using C-labeled glucoses

In order to elucidate the biosynthetic process of cellulose and curdlan, ¹³C-labeled polysaccharides were biosynthesized by Acetobacter xylinum (IFO 13693) and Agrobacterium sp. (ATCC 31749), from culture media containing -(1-¹³C)glucose, -(2-¹³C)glucose, -(4-¹³C)glucose, or -(6-¹³C)glucose as the carbon source, and their structures were determined by ¹³C NMR spectroscopy. The labeling was mainly found in the original position, indicating direct polymerization of introduced glucoses. In addition, the transfer of labeling from C-2 to C-1, C-3 and C-5, from C-4 to C-1, C-2 and C-3, and from C-6 to C-1 was found in celluloses. In curdlan, the transfer of labeling from C-1 to C-3, from C-2 to C-1 and C-3, from C-4 to C-1, C-2 and C-3, and from C-6 to C-1 and C-3 was observed. From analysis of this labeling, the biosynthetic process of cellulose and curdlan was explained as involving six routes. The percentages of each route via which cellulose or curdlan is biosynthesized were estimated for upper (C-1 to C-3) and lower portions (C-4 to C-6) of glucosidic units in the polysaccharides. It is noted that very few polysaccharides are formed via the Embden-Meyerhof pathway. The lower half (C-4 to C-6) structure of introduced glucoses is well preserved in the polysaccharides.     

Contribution of central versus sweat gland mechanisms to the seasonal change of sweating function in young sedentary males and females

In summer and winter, young, sedentary male (N = 5) and female (N = 7) subjects were exposed to heat in a climate chamber in which ambient temperature (Ta) was raised continuously from 30 to 42°C at a rate of 0.1°C min⁻¹ at a relative humidity of 40%. Sweat rates (SR) were measured continuously on forearm, chest and forehead together with tympanic temperature (Tty), mean skin temperature ( [`T] s ) \left( {\overline {\hbox{T}} {\hbox{s}}} \right) and mean body temperature ( [`T] b ) \left( {\overline {\hbox{T}} {\hbox{b}}} \right) . The rate of sweat expulsions (Fsw) was obtained as an indicator of central sudomotor activity. Tty and ( [`T] b ) \left( {\overline {\hbox{T}} {\hbox{b}}} \right) were significantly lower during summer compared with winter in males; SR was not significantly different between summer and winter in males, but was significantly higher during summer in females; SR during winter was higher in males compared with females. The regression line relating Fsw to ( [`T] b ) \left( {\overline {\hbox{T}} {\hbox{b}}} \right) shifted significantly from winter to summer in males and females, but the magnitude of the shift was not significantly different between the two subject groups. The regression line relating SR to Fsw was steepened significantly from winter to summer in males and females, and the change in the slope was significantly greater in females than in males. Females showed a lower slope in winter and a similar slope in summer compared to males. It was concluded that sweating function was improved during summer mediated by central sudomotor and sweat gland mechanisms in males and females, and, although the change of sweat gland function from winter to summer was greater in females as compared with males, the level of increased sweat gland function during summer was similar between the two subject groups.     

Uncoupling and endocytosis of 5-hydroxytryptamine 4 receptors. Distinct molecular events with different GRK2 requirements

The 5-hydroxytryptamine type 4 receptors (5-HT4Rs) are involved in memory, cognition, feeding, respiratory control, and gastrointestinal motility through activation of a G(s)/cAMP pathway. We have shown that 5-HT4R undergoes rapid and profound homologous uncoupling in neurons. However, no significant uncoupling was observed in COS-7 or HEK293 cells, which expressed either no or a weak concentration of GRK2, respectively. High expression of GRK2 in neurons is likely to be the reason for this difference because overexpression of GRK2 in COS-7 and HEK293 cells reproduced rapid and profound uncoupling of 5-HT4R. We have also shown, for the first time, that GRK2 requirements for uncoupling and endocytosis were very different. Indeed, beta-arrestin/dynamin-dependent endocytosis was observed in HEK293 cells without any need of GRK2 overexpression. In addition to this difference, uncoupling and beta-arrestin/dynamin-dependent endocytosis were mediated through distinct mechanisms. Neither uncoupling nor beta-arrestin/dynamin-dependent endocytosis required the serine and threonine residues localized within the specific C-terminal domains of the 5-HT4R splice variants. In contrast, a cluster of serines and threonines, common to all variants, was an absolute requirement for beta-arrestin/dynamin-dependent receptor endocytosis, but not for receptor uncoupling. Furthermore, beta-arrestin/dynamin-dependent endocytosis and uncoupling were dependent on and independent of GRK2 kinase activity, respectively. These results clearly demonstrate that the uncoupling and endocytosis of 5-HT4R require different GRK2 concentrations and involve distinct molecular events.     

Increased Serum LIGHT Levels Correlate with Disease Progression and Severity of Interstitial Pneumonia in Patients with Dermatomyositis: A Case Control Study

BackgroundActivated CD8+ T cells play an important role in the pathogenesis of dermatomyositis (DM) with interstitial pneumonia (IP). Serum CD8+ T-cell activator, LIGHT, and Th1/Th2/Th17 cytokines were measured in DM-IP patients and compared with clinical parameters to investigate their usefulness.MethodsThe correlations between the clinical findings and serum LIGHT and Th1/Th2/Th17 cytokine levels were investigated in 21 patients with DM-IP (14 with rapidly progressive IP [RPIP] and 7 with chronic IP [CIP], including 4 fatal cases of IP).ResultsThe median serum LIGHT level was 119 (16–335.4) pg/ml, which was higher than that in healthy control subjects and DM patients without IP. The median serum IL–6 level was 14.7 (2.4–154.5) pg/ml (n = 13). The other cytokines were detected in only a few patients. The median serum LIGHT level in DM-RPIP patients (156 [49.6–335.4] pg/ml) was significantly higher than that in DM-CIP patients (94.3 [16–164.2] pg/ml) (P = 0.02). The serum IL–6 level did not correlate with either progression or outcome of DM-IP. ROC curve analysis determined a serum LIGHT level of ≥120 pg/ml to be the cut-off value for the rapid progression of DM-IP. Serum LIGHT levels correlated significantly with %DLco (R = 0.55, P = 0.04) and total ground-glass opacity scores (R = 0.72, P = 0.0002). The serum LIGHT level significantly decreased to 100.5 (12.4–259.3) pg/ml 4 weeks after treatment initiation (P = 0.04).ConclusionsThe serum LIGHT level may be a promising marker of disease progression and severity in patients with DM-IP.     

miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis

miR-146a plays important roles in cancer as it directly targets NUMB, an inhibitor of Notch signaling. miR-146a is reportedly regulated by a G>C polymorphism (SNP; rs2910164). This polymorphism affects various cancers, including colorectal cancer (CRC). However, the clinical significance of miR-146a polymorphism in CRC remains unclear. A total of 59 patients with CRC were divided into 2 groups: a CC/CG genotype (n = 32) and a GG genotype (n = 27), based on the miR-146a polymorphism. cDNA microarray analysis was performed using 59 clinical samples. Significantly enriched gene sets in each genotype were extracted using GSEA. We also investigated the association between miR-146a polymorphism and miR-146a, NUMB expression or migratory response in CRC cell lines. The CC/CG genotype was associated with significantly more synchronous liver metastasis (p = 0.007). A heat map of the two genotypes showed that the expression profiles were clearly stratified. GSEA indicated that Notch signaling and JAK/STAT3 signaling were significantly associated with the CC/CG genotype (p = 0.004 and p = 0.023, respectively). CRC cell lines with the pre-miR-146a/C revealed significantly higher miR-146a expression (p = 0.034) and higher NUMB expression and chemotactic activity. In CRC, miR-146a polymorphism is involved in liver metastasis. Identification of this polymorphism could be useful to identify patients with a high risk of liver metastasis in CRC.     

The Nutritional Value of D-Amino Acid in the Chick Nutrition

The nutritional values of 16 D-amino acids in chick growth were studied on the purified diets containing crystalline amino acids as a sole source of nitrogen. Growth rate, feed consumption and nitrogen retention were measured. The nutritional values of D-amino acids were studied by comparing individually with the control groups fed on the diet containing all L-amino acids and negative control groups fed with the diet omitted the corresponding L-isomer. The following results were obtained. Essential amino acids: 1. Equal or almost equal nutritional value to the corresponding L-isomer; methionine, phenylalanine, leucine, proline. 2. Half nutritional value compared with L-isomer; valine. 3. Small nutritional value compared with L-isomer; tryptophan, isoleucine, histidine. 4. No nutritional value; lysine, threonine, arginine. Non-essential amino acid: 1. Equal or almost equal nutritional value to the corresponding L-isomer; serine, tyrosine, cystine. 2. There is a possibility that it has a slight growth retardation effect; alanine. 3. The growth retardation effect was found; aspartic acid.