Atrial natriuretic peptide in the dog with mitral regurgitation.

The concentration and molecular form of the plasma atrial natriuretic peptide (ANP) in dogs with mitral regurgitation was investigated. Plasma ANP concentration in dogs with mitral regurgitation was significantly increased (29.4 +/- 1.88 pmol litre-1, n = 40) compared to that in the controls (14.5 +/- 0.62 pmol litre-1, n = 20, P less than 0.01). Molecular forms of plasma ANP were determined by the gel permeation chromatogram. A single peak corresponding to alpha-ANP was detected in the plasma from the controls. However, a peak corresponding to beta-ANP and, or, gamma-ANP was detected in the plasma of the dogs with mitral regurgitation in addition to alpha-ANP. These results suggest that the process of ANP synthesis was altered and excretion of ANP from the heart was enhanced in dogs with mitral regurgitation.     

Anatomically corrected malposition (ACM) with subpulmonary infundibulum in a calf: clinico-morphologic case report.

A Japanese black calf with cyanosis, tachycardia, tachypnea and systolic murmur died of hypoxemia and cardiac insufficiency on the 38th day after birth. We could not establish the diagnosis during it's life. However, anatomically corrected malposition (ACM) with ventricular septal defect was confirmed at autopsy. There was situs solitus of the viscera and atria with atrio-ventricular discordance and ventriculo-arterial concordance. The ventricles demonstrated l-loop, i.e. on the right-sided ventricle there was a markedly enlarged morphologic left ventricle, and on the left-sided ventricle there was a hypoplastic morphologic right ventricle with a stenotic tricuspid valve and Ebstein-like deformity. The right posterior aorta originated from the left ventricle. The pulmonary artery arose from the left-sided right ventricle via infundibulum. There was a fibrous continuity between the aortic and mitral valve. We considered that this is the first reported case of bovine ACM.     

Toxicogenomic biomarkers for liver toxicity

Toxicogenomics (TGx) is a widely used technique in the preclinical stage of drug development to investigate the molecular mechanisms of toxicity. A number of candidate TGx biomarkers have now been identified and are utilized for both assessing and predicting toxicities. Further accumulation of novel TGx biomarkers will lead to more efficient, appropriate and cost effective drug risk assessment, reinforcing the paradigm of the conventional toxicology system with a more profound understanding of the molecular mechanisms of drug-induced toxicity. In this paper, we overview some practical strategies as well as obstacles for identifying and utilizing TGx biomarkers based on microarray analysis. Since clinical hepatotoxicity is one of the major causes of drug development attrition, the liver has been the best documented target organ for TGx studies to date, and we therefore focused on information from liver TGx studies. In this review, we summarize the current resources in the literature in regard to TGx studies of the liver, from which toxicologists could extract potential TGx biomarker gene sets for better hepatotoxicity risk assessment.     

Saccharification of cellulose by dry pyrolysis

Pyrolysis of cellulose was studied for the purpose of practical production of 1,6-anhydro-β-D-glucopyranoside (levoglucosan, LG). To minimize secondary degradation of levoglucosan, two methods were examined: (1) conductive heating by glass bottle, and (2) radiation heating from the surface by CO₂ laser beam, both under vacuum and in a nitrogen atmosphere. Glass-bottle pyrolysis under vacuum gave levoglucosan yield of 50%–55% in the optimum temperature range of 350°–410°C, where placing the cold trap in the vicinity of heated area was effective in improving the yield. In contrast, glass-bottle pyrolysis under nitrogen gave low yields of 17%–20%, probably due to slower diffusion of pyrolysis product from hot region. The CO₂ laser pyrolysis under vacuum gave the product as aerosol (white smoke), causing difficulty in recovery of the product, and the maximum yield was 5%–17%. In this case the treatment under nitrogen flow was effective for recovery of aerosol, and the maximum yield reached approximately 25%.     

Detection of QTLs for white-back and basal-white grains caused by high temperature during ripening period in japonica rice

There is increasing evidence that global warming affects the development of rice. High temperatures during ripening increase the ratio of undesirable chalky grains followed by deteriorating grain appearance quality. In order to detect quantitative trait loci (QTLs) controlling the occurrence of white-back and basal-white chalky grains of brown rice, QTL analysis was performed using recombinant inbred lines derived from a cross between two strains, ‘Tsukushiroman’ (sensitive to heat stress) and ‘Chikushi 52’ (tolerant of heat stress). The F₇ and F₈ lines were exposed to heat stress during the ripening period in two locations, Fukuoka and Kagoshima, in Japan. QTLs for white-back grains and basal-white grains were detected on chromosomes 1, 3, and 8, and those for basal-white grains were detected on chromosomes 2, 3, and 12. QTLs on chromosome 8 for white-back grains were shared in the plants grown in both locations. Near-isogenic lines (NILs), which harbored a segment from ‘Chikushi 52’ on chromosome 8 with the genetic background of ‘Tsukushiroman’, showed relatively lower ratios of white-back grains than ‘Tsukushiroman’. Therefore, insertion of the ‘Chikushi 52’ genomic region of the QTL on chromosome 8 can improve the quality of rice when it is grown under heat stress conditions.     

Effects of intramammary infusion of Bifidobacterium breve on mastitis pathogens and somatic cell response in quarters from dairy cows with chronic subclinical mastitis

The present study assessed the effects of intramammary infusion of Bifidobacterium breve (B. breve) on mastitis‐causing pathogens and on the somatic cell counts (SCC) in lactating cows with chronic subclinical mastitis. The bacteriological cure rates of 42 quarters from 42 cows infected with Staphylococcus aureus, Corynebacterium bovis, coagulase‐negative staphylococci, and environmental streptococci were 18.2% (2/11), 14.3% (1/7), 58.8% (10/17), and 28.6% (2/7), respectively, on day 14 after B. breve infusion. In a second trial, B. breve was infused into 18 quarters from 18 cows with chronic subclinical mastitis from which pathogens had not been isolated; the rates of quarters showing SCC > 50 × 10⁴ cells/ml prior to B. breve infusion that decreased to < 30 × 10⁴ cells/ml after infusion were significantly (p < .01) increased to 61.1% (11/18) on day 14 compared to that prior to infusion (0/18). The intramammary infusion of B. breve appears to be a non‐antibiotic approach for elimination of minor pathogens and decreasing SCC in quarters with chronic subclinical mastitis in dairy cows.     

Polar cardenolide monoglycosides from stems and twigs of Nerium oleander and their biological activities

Twelve polar cardenolide monoglycosides, 1, 2, 4?C13, and oleagenin (3) were isolated from the methanol extract of stems and twigs of Nerium oleander. Among these, oleagenin (3) and cardenolide monoglycosides named cardenolide B-1 (1) and cardenolide B-2 (2) were isolated from natural sources for the first time. The in vitro antiinflammatory activity of compounds 1?C13 was examined on the basis of inhibitory activity against the induction of the intercellular adhesion molecule-1 (ICAM-1). Compounds 4?C7 were active at an IC₅₀ value of less than 0.4 ??M. The cytotoxic activity of compounds 1?C13 was evaluated against three human cell lines: normal human fibroblast cells (WI-38), malignant tumor cells derived from WI-38 (VA-13), and human liver tumor cells (HepG2). Compounds 4, 6, and 7 were active toward these three cell lines at IC₅₀ values of less than 0.7 ??M, and compounds 5 and 8 were active toward the cell lines at IC₅₀ values of less than 1.5 ??M. The multidrug resistance (MDR) cancer-reversal activity of compounds 1?C13 was evaluated on the basis of the amount of calcein accumulated in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compound 1 and 12 showed significant effects on calcein accumulation.     

Superelastic effect in polycrystalline ferrous alloys

In superelastic alloys, large deformation can revert to a memorized shape after removing the stress. However, the stress increases with increasing temperature, which limits the practical use over a wide temperature range. Polycrystalline Fe-Mn-Al-Ni shape memory alloys show a small temperature dependence of the superelastic stress because of a small transformation entropy change brought about by a magnetic contribution to the Gibbs energies. For one alloy composition, the superelastic stress varies by 0.53 megapascal/°C over a temperature range from -196 to 240°C.     

High-speed atomic force microscopy reveals rotary catalysis of rotorless F₁-ATPase

F(1) is an adenosine triphosphate (ATP)-driven motor in which three torque-generating β subunits in the α(3)β(3) stator ring sequentially undergo conformational changes upon ATP hydrolysis to rotate the central shaft γ unidirectionally. Although extensive experimental and theoretical work has been done, the structural basis of cooperative torque generation to realize the unidirectional rotation remains elusive. We used high-speed atomic force microscopy to show that the rotorless F(1) still "rotates"; in the isolated α(3)β(3) stator ring, the three β subunits cyclically propagate conformational states in the counterclockwise direction, similar to the rotary shaft rotation in F(1). The structural basis of unidirectionality is programmed in the stator ring. These findings have implications for cooperative interplay between subunits in other hexameric ATPases.     

Traffic jams reduce hydrolytic efficiency of cellulase on cellulose surface

A deeper mechanistic understanding of the saccharification of cellulosic biomass could enhance the efficiency of biofuels development. We report here the real-time visualization of crystalline cellulose degradation by individual cellulase enzymes through use of an advanced version of high-speed atomic force microscopy. Trichoderma reesei cellobiohydrolase I (TrCel7A) molecules were observed to slide unidirectionally along the crystalline cellulose surface but at one point exhibited collective halting analogous to a traffic jam. Changing the crystalline polymorphic form of cellulose by means of an ammonia treatment increased the apparent number of accessible lanes on the crystalline surface and consequently the number of moving cellulase molecules. Treatment of this bulky crystalline cellulose simultaneously or separately with T. reesei cellobiohydrolase II (TrCel6A) resulted in a remarkable increase in the proportion of mobile enzyme molecules on the surface. Cellulose was completely degraded by the synergistic action between the two enzymes.