Crystal structure of SUMO-3-modified thymine-DNA glycosylase

Modification of cellular proteins by the small ubiquitin-like modifier SUMO is important in regulating various cellular events. Many different nuclear proteins are targeted by SUMO, and the functional consequences of this modification are diverse. For most proteins, however, the functional and structural consequences of modification by specific SUMO isomers are unclear. Conjugation of SUMO to thymine-DNA glycosylase (TDG) induces the dissociation of TDG from its product DNA. Structure determination of the TDG central region conjugated to SUMO-1 previously suggested a mechanism in which the SUMOylation-induced conformational change in the C-terminal region of TDG releases TDG from tight binding to its product DNA. Here, we have determined the crystal structure of the central region of TDG conjugated to SUMO-3. The overall structure of SUMO-3-conjugated TDG is similar to the previously reported structure of TDG conjugated to SUMO-1, despite the relatively low level of amino acid sequence similarity between SUMO-3 and SUMO-1. The two structures revealed that the sequence of TDG that resembles the SUMO-binding motif (SBM) can form an intermolecular beta-sheet with either SUMO-1 or SUMO-3. Structural comparison with the canonical SBM shows that this SBM-like sequence of TDG retains all of the characteristic interactions of the SBM, indicating sequence diversity in the SBM.     

Human plasma adenosine deaminase 2 is secreted by activated monocytes

Adenosine deaminase (ADA) plays an important role in the immune system, and its activity is composed of two kinetically distinct isozymes, ADA1 and ADA2. ADA2 is a major component of human plasma total ADA activity and ADA2 activity is significantly elevated in patients with various diseases such as HIV infection and chronic hepatitis. However, relatively little is known about ADA2 because of difficulties in purifying this enzyme. In this study we succeeded in purifying human plasma ADA2 and demonstrate the extracellular secretion of ADA2 from human peripheral blood monocytes stimulated with phorbol 12-myristate 13-acetate and calcium ionophore.     

Computational analysis of blood flow in an integrated model of the left ventricle and the aorta

To study the effects of intraventricular flow dynamics on the aortic flow, we created an integrated model of the left ventricle and aorta and conducted a computer simulation of diastolic and systolic blood flow within this model. The results demonstrated that the velocity profile at the aortic annulus changed dynamically, and was influenced by the intraventricular flow dynamics. The profile was almost flat in early systole but became nonuniform as systole progressed, and was skewed toward the posterior side in midsystole and toward the anterior side in later systole. At a distance from the aortic annulus, a different velocity profile was induced by the twisting and torsion of the aorta. In the ascending aorta, the fastest flow was initially located in the posteromedial sector, and it moved to the posterior section along the circumference as systole progressed. The nonuniformity of the aortic inflow gave rise to a complex wall shear stress (WSS) distribution in the aorta. A comparison of the WSS distribution obtained in this integrated analysis with that obtained in flow calculations using an isolated aorta model with Poiseuille and flat inlet conditions showed that intraventricular flow affected the WSS distribution in the ascending aorta. These results address the importance of an integrated analysis of flow in the left ventricle and aorta.     

Ternary Cu(II) complexes, Cu(H(-1)L)(ACys-) and Cu(H(-2)L)(ACys-); L = peptides, ACys- = N-acetyl-cysteinate. Analogous complexes to the intermediates in the transport of Cu(II) from Cu(H(-2)L) to cysteine

The Cu(II) in Cu(H(-2)L) has been postulated to be successively transported to cysteine (Cys) as follows; Cu(H(-2)L) <==> Cu(H(-2)L)(Cys*-) <==> Cu(H(-1)L)(Cys*-) --> Cu(H(-1)L)(Cys-), where Cys*- denotes the monodentate Cys-. N-acetyl-cysteinate (ACys-) complexes Cu(H(-2)L)(ACys-) and Cu(H(-1)L)(ACys-), having similar coordination modes to Cu(H(-2)L)(Cys*-) and Cu(H(-1)L)(Cys*-), respectively, exhibited the S --> Cu(II) charge transfer absorption at 325-355 nm and the d-d absorption at 530-610 nm. A linear interrelation existed between the energies of the CD and d-d absorptions. Cu(H(-2)L)(ACys-) were in rapid equilibrium with Cu(H(-1)L)(ACys-). Upon forming the ternary complex, pK(c2) of the parent Cu(H(-1)L) was raised to more than 1.0. The formation constants (K) of the Cu(H(-1)L)(ACys-) species from Cu(H(-1)L) were bigger than those of Cu(H(-2)L)(ACys-) from Cu(H(-2)L). The linear free-energy relationship existed between the free-energy change (deltaG) and the entropy change (deltaS) for the ternary complex formation. The rate constants (k1+) for the Cu(H(-1)L)(Cys-) formation closely correlated with the K values for Cu(H(-2)L)(ACys-). The ternary complexes containing ACys are considered to be analogous complexes to the intermediates in the transport of Cu(II) from peptides to cysteine.     

Fructooligosaccharides consumption inhibits the loss of iron from the incisor enamel surface in gastrectomized rat

We examine the effects of fructooligosaccharides (FOS) on the reduction in the incisor iron content in gastrectomized rat. Twenty-eight 5-wk-old male Sprague-Dawley rats were divided into two groups: sham operated (bSH) and gastrectomized (bGX). After 4 wk each group was divided into two subgroups according to the presence or absence of 7.5% FOS in the synthetic diet (SH, SH+FOS, GX, and GX+FOS). At 10 wk wafter surgery, the maxilla was prepared to examine the iron content of the incisor enamel surface at four points. These points corresponded to the iron content at 6,7,8, and 10 wk, respectively. Blood was collected to determine serum iron levels at 4 and 10 wk. The serum iron level significantly decreased at 4 and 10 wk the GX group. At 10 wk, the level in the GX+FOS group significantly increased but did not reaach that in the SH group. The iron content of the enamel surface time-dependently increased and no significant differences were seen between SH and GX+FOS at 8 and 10 wk. These results suggest that FOS consumption impaired the loss of enamel content following gastrectomy, and this effect preceded the effect on the serum iron level.     

Cell type-specific activation of metabolism reveals that beta-cell secretion suppresses glucagon release from alpha-cells in rat pancreatic islets

Abnormal glucagon secretion is often associated with diabetes mellitus. However, the mechanisms by which nutrients modulate glucagon secretion remain poorly understood. Paracrine modulation by beta- or delta-cells is among the postulated mechanisms. Herein we present further evidence of the paracrine mechanism. First, to activate cellular metabolism and thus hormone secretion in response to specific secretagogues, we engineered insulinoma INS-1E cells using an adenovirus-mediated expression system. Expression of the Na+-dependent dicarboxylate transporter (NaDC)-1 resulted in 2.5- to 4.6-fold (P < 0.01) increases in insulin secretion in response to various tricarboxylic acid cycle intermediates. Similarly, expression of glycerol kinase (GlyK) increased insulin secretion 3.8- or 4.2-fold (P < 0.01) in response to glycerol or dihydroxyacetone, respectively. This cell engineering method was then modified, using the Cre-loxP switching system, to activate beta-cells and non-beta-cells separately in rat islets. NaDC-1 expression only in non-beta-cells, among which alpha-cells are predominant, caused an increase (by 1.8-fold, P < 0.05) in glucagon secretion in response to malate or succinate. However, the increase in glucagon release was prevented when NaDC-1 was expressed in whole islets, i.e., both beta-cells and non-beta-cells. Similarly, an increase in glucagon release with glycerol was observed when GlyK was expressed only in non-beta-cells but not when it was expressed in whole islets. Furthermore, dicarboxylates suppressed basal glucagon secretion by 30% (P < 0.05) when NaDC-1 was expressed only in beta-cells. These data demonstrate that glucagon secretion from rat alpha-cells depends on beta-cell activation and provide insights into the coordinated mechanisms underlying hormone secretion from pancreatic islets.     

Association between high voltage overhead transmission lines and mental health: a cross-sectional study

We examined the association between residential proximity to 60 Hz high voltage (22-500 kV) overhead transmission lines (HVOTLs) and mental health (MH). The subjects were 223 mothers with a mean age of 37 years. The distance from the subject's residence to the closest HVOTL was measured on a map. MH status was assessed by the SF-36 Health Survey, which was scored on a 0-100 point scale, and an individual with a score of 52 points or less was defined as having poor MH. Logistic regression models were used to examine the association between the distance from the subjects' residence to the closest HVOTL and MH status. The prevalence of poor MH was 15%. Among the 223 subjects, 10 lived within 100 m of a HVOTL. The adjusted odds ratios (OR) for poor MH among those who lived 101-300 m or within 100 m from HVOTL were 1.29 (95% confidence interval (CI): 0.35-10.13) and 1.87 (95% CI: 0.35-10.13), respectively, against the reference category (300+ m). MH status was not significantly associated with the distance between the subject's residence and the closest HVOTL.     

Plumage color as a status signal in male–male interaction in the red-flanked bushrobin, Tarsiger cyanurus

Recent studies have suggested that structural-based coloration is an honest signal of male genetic and/or conditional quality in sexual selection. However, whether structural coloration functions in intrasexual competition is unknown. We examined whether plumage color functions as a status signal during intrasexual interactions in the red-flanked bushrobin Tarsiger cyanurus; adult males have many blue plumes as structural coloration whereas yearling males and females are olive brown with few blue plumages. Blue males did not always dominate olive-brown males. The number of interactions did not differ with the colors of the two birds involved. The interactions of a blue male and an olive-brown male were less aggressive than those of two blue or of two olive-brown males. In this study, we found that structural plumage coloration may serve as a signal of aggressive intent and lower the escalation level of an aggressive interaction in a manner consistent with hypotheses regarding the evolution of delayed plumage maturation.     

Spawning habitat selection and suitability for Japanese dace, Tribolodon hakonensis

We have investigated the effects of three current velocities and three substrate sizes (gravel to cobble) on the spawning behavior of Japanese dace, Tribolodon hakonensis, in spawning-induction and habitat-selection experiments. In the spawning-induction experiment under laboratory conditions the number of females induced to spawn was significantly fewer at low current velocity (ca. 5 cm s^–1) than at medium (ca. 30 cm s^–1) or high (ca. 50 cm s^–1) current velocity. Females spawned independently of substrate size in the experimental tank, and did not bury their eggs in the substrate bed. In the habitat-selection experiment under field conditions, females selected the substrate microhabitat and spawned more frequently at a site with medium substrate size (very coarse gravel; major axis ca. 40 mm) than at sites with small (fine gravel; ca. 8 mm) or large (cobble; ca. 70 mm) substrate size. We conclude that Japanese dace select spawning sites at least partly on the basis of current velocity and substrate size, which affects the survival rate of eggs.