Unsymmetrical hot electron heating in quasi-ballistic nanocontacts.

Electrons are allowed to pass through a single atom connected to two electrodes without being scattered as the characteristic size is much smaller than the inelastic mean free path. In this quasi-ballistic regime, it is difficult to predict where and how power dissipation occurs in such current-carrying atomic system. Here, we report direct assessment of electrical heating in a metallic nanocontact.

Single-molecule sensing electrode embedded in-plane nanopore.

Electrode-embedded nanopore is considered as a promising device structure for label-free single-molecule sequencing, the principle of which is based on nucleotide identification via transverse electron tunnelling current flowing through a DNA translocating through the pore. Yet, fabrication of a molecular-scale electrode-nanopore detector has been a formidable task that requires atomic-level alignment of a few nanometer sized pore and an electrode gap. Here, we report single-molecule detection using a nucleotide-sized sensing electrode embedded in-plane nanopore.

Oral toxicological studies of black soybean (Glycine max) hull extract: acute studies in rats and mice, and chronic studies in mice.

Black soybean (Glycine max) has been used for traditional medicine and food in Asian countries, but safety of its hull has not been studied. We conducted acute and chronic oral toxicity studies. For the acute study, an extract of black soybean hull (BE; 2.

Gate manipulation of DNA capture into nanopores.

Understanding biophysics governing DNA capture into a nanopore and establishing a manipulation system for the capture process are essential for nanopore-based genome sequencing. In this work, the functionality of extended electric field and electroosmotic flow (EOF) during the capture stage and their dependence on gate voltage, U(G), are investigated. We demonstrate that while both the electric field and EOF within a cis chamber make long-distance contributions to DNA capture around the pore mouth, the former effect is always capturing, while the latter causes trapping or blocking of the molecule depending on the magnitude of the gate voltage, U(G): an anionic EOF induced by high U(G) is capable of doubling the DNA trapping speed and thus the absorption radius in the cis chamber, whereas a cationic EOF by low U(G) would substantially offset the trapping effort by the electric field and even totally block DNA entrance into the pore.

Crucial vasculoprotective role of the whole nitric oxide synthase system in vascular lesion formation in mice: Involvement of bone marrow-derived cells.

Although all three nitric oxide (NO) synthases (nNOS, iNOS, and eNOS) are expressed in injured arteries, it remains to be elucidated the role of the NOSs in their entirety in the vascular lesion formation. We addressed this issue in mice deficient in all NOS genes. Vascular injury was induced by permanent ligation of a unilateral carotid artery in wild-type (WT), singly, and triply NOS(-/-) mice.

Reduced spinal microglial activation and neuropathic pain after nerve injury in mice lacking all three nitric oxide synthases.

Background: Several studies have investigated the involvement of nitric oxide (NO) in acute and chronic pain using mice lacking a single NO synthase (NOS) gene among the three isoforms: neuronal (nNOS), inducible (iNOS) and endothelial (eNOS). However, the precise role of NOS/NO in pain states remains to be determined owing to the substantial compensatory interactions among the NOS isoforms. Therefore, in this study, we used mice lacking all three NOS genes (n/i/eNOS-/-mice) and investigated the behavioral phenotypes in a series of acute and chronic pain assays.

Dependence of single-molecule conductance on molecule junction symmetry.

The symmetry of a molecule junction has been shown to play a significant role in determining the conductance of the molecule, but the details of how conductance changes with symmetry have heretofore been unknown. Herein, we investigate a naphthalenedithiol single-molecule system in which sulfur atoms from the molecule are anchored to two facing gold electrodes. In the studied system, the highest single-molecule conductance, for a molecule junction of 1,4-symmetry, is 110 times larger than the lowest single-molecule conductance, for a molecule junction of 2,7-symmetry.

Controlling DNA translocation through gate modulation of nanopore wall surface charges.

One major challenge of nanopore-based DNA sequencing technology is to find an efficient way to reduce DNA translocation speed so that each nucleotide can reside long enough in the pore for interrogation. Here we report the electrical tuning of DNA translocation speed by gate modulation of nanopore wall surface charges. We find that native surface-charge-induced counterions in the electroosmotic layer substantially enhance advection flow of fluid, which exerts stronger dragging forces on the translocating DNA, and thereby lowering the DNA translocation speed.

Increasing dihydrobiopterin causes dysfunction of endothelial nitric oxide synthase in rats in vivo.

An elevation of oxidized forms of tetrahydrobiopterin (BH(4)), especially dihydrobiopterin (BH(2)), has been reported in the setting of oxidative stress, such as arteriosclerotic/atherosclerotic disorders, where endothelial nitric oxide synthase (eNOS) is dysfunctional, but the role of BH(2) in the regulation of eNOS activity in vivo remains to be evaluated. This study was designed to clarify whether increasing BH(2) concentration causes endothelial dysfunction in rats. To increase vascular BH(2) levels, the BH(2) precursor sepiapterin (SEP) was intravenously given after the administration of the specific dihydrofolate reductase inhibitor methotrexate (MTX) to block intracellular conversion of BH(2) to BH(4).

Long-term outcome of idiopathic hypertrophic thoracic pachymeningitis.

Idiopathic hypertrophic spinal pachymeningitis (IHSP) is a comparatively rare disease characterized by hypertrophic inflammation of the dura mater and clinical symptoms that progress from local pain to myelopathy. We report a case of IHSP followed up for 20 years in a 46-year-old man. Expansive laminoplasty was performed in 1991, and this case has been previously reported by a co-author.

Electrical detection of single methylcytosines in a DNA oligomer.

We report label-free electrical detections of chemically modified nucleobases in a DNA using a nucleotide-sized electrode gap. We found that methyl substitution contributes to increase the tunneling conductance of deoxycytidines, which was attributed to a shift of the highest occupied molecular orbital level closer to the electrode Fermi level by methylation. We also demonstrate statistical identifications of methylcytosines in an oligonucleotide by tunneling current.

Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle.

In obese patients with type 2 diabetes, insulin delivery to and insulin-dependent glucose uptake by skeletal muscle are delayed and impaired. The mechanisms underlying the delay and impairment are unclear. We demonstrate that impaired insulin signaling in endothelial cells, due to reduced Irs2 expression and insulin-induced eNOS phosphorylation, causes attenuation of insulin-induced capillary recruitment and insulin delivery, which in turn reduces glucose uptake by skeletal muscle.

Histamine deficiency decreases atherosclerosis and inflammatory response in apolipoprotein E knockout mice independently of serum cholesterol level.

Objective: Histamine and histamine receptors are found in atherosclerotic lesions, and their signaling and subsequent proatherogenic or proinflammatory gene expression are involved in atherogenesis. In the present study, we generated apolipoprotein E (apoE) and histamine synthesizing histidine decarboxylase double knockout (DKO) mice on a C57BL/6J (wild-type mice) background to clarify the roles of histamine in atherosclerosis.

Methods And Results: Wild-type, apoE knockout (KO), and DKO mice were fed a high-cholesterol diet to analyze hyperlipidemia-induced atherosclerosis.

Single-molecule identification via electric current noise.

Label-free and real-time single-molecule detection may aid the development of high-throughput biosensing platforms. Molecular fluctuations are a source of noise that often hinders single-molecule identification by obscuring the fine details of molecular identity. In this study, we report molecular identification through direct observation of quantum-fluctuation-induced inelastic noise in single organic molecules.

Laparoscopy-assisted total gastrectomy for advanced gastric cancer with carcinomatous ascites after S1 plus cisplatin chemotherapy: a case report.

A 29-year-old man with a type 4 tumor, in the lower third of the stomach, and carcinomatous ascites was diagnosed by aspiration cytology of the ascitic fluid. Curative resection was considered impossible, and S1 (120 mg/d) and cisplatin (90 mg/d) were given for 21 days in 1 course. The cancer lesion showed marked remission (partial response), and the ascites completely disappeared after the fourth course.

Molecule-electrode bonding design for high single-molecule conductance.

We report the application of an intermolecular interaction design for organic conductor crystals with a high conductance to a molecule-electrode design for a high single-molecule conductance by using dithiol and diselenol terthiophenes. We found that dithiol and diselenol single-molecule junctions show the highest single-molecule conductance among single-molecule junctions with Au-S and Au-Se bonds, and that diselenol single-molecule junctions have a higher single-molecule conductance than dithiol ones. We demonstrate that replacing S atoms with Se atoms is a promising molecule-electrode bonding design for a high single-molecule conductance.

Complete disruption of all nitric oxide synthase genes causes markedly accelerated renal lesion formation following unilateral ureteral obstruction in mice in vivo.

The role of nitric oxide (NO) derived from all three NO synthases (NOSs) in renal lesion formation remains to be fully elucidated. We addressed this point in mice lacking all NOSs. Renal injury was induced by unilateral ureteral obstruction (UUO).

Spontaneous development of left ventricular hypertrophy and diastolic dysfunction in mice lacking all nitric oxide synthases.

Background: The role of the nitric oxide synthase (NOS) system in cardiac architecture and function remains unknown. This point was addressed in mice that lack all 3 NOS genes.

Methods And Results: Morphological, echocardiographic, and hemodynamic analyses were performed in wild-type (WT), singly nNOS(-/-), iNOS(-/-), eNOS(-/-), and triply n/i/eNOS(-/-) mice.

Efficient detection of hepatocellular carcinoma by a hybrid blood test of epigenetic and classical protein markers.

Background: There are few blood tests for an efficient detection of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection.

Methods: The abilities of quantitative analyses of 7 genes hypermethylation in serum DNA, α-fetoprotein (AFP) and prothrombin-induced vitamin K absence II (PIVKA-II), and various combinations to detect HCC were evaluated in a training cohort of 164 HCV-infected patients (108 HCCs; 56 non-HCCs). An optimal hybrid detector, built using data for 2 methylated genes (SPINT2 and SRD5A2), AFP, and PIVKA-II, achieved the most satisfactory ability to detect HCC in the training cohort.

Pathophysiological relevance of NO signaling in the cardiovascular system: novel insight from mice lacking all NO synthases.

Nitric oxide (NO) exerts a variety of biological actions under both physiological and pathological conditions. NO is synthesized by three distinct NO synthase (NOS) isoforms, including neuronal (nNOS), inducible (iNOS), and endothelial NOS (eNOS), all of which are expressed in the human cardiovascular system. The roles of endogenous NO in the cardiovascular system have been investigated in pharmacological studies with NOS inhibitors and in studies with mice that lack each NOS isoform.

Upregulation of norepinephrine transporter function by prolonged exposure to nicotine in cultured bovine adrenal medullary cells.

Nicotine acts on nicotinic acetylcholine receptors in the adrenal medulla and brain, thereby stimulating the release of monoamines such as norepinephrine (NE). In the present study, we examined the effects of prolonged exposure to nicotine on NE transporter (NET) activity in cultured bovine adrenal medullary cells. Treatment of adrenal medullary cells with nicotine increased [(3)H]NE uptake in both a time- (1-5 days) and concentration-dependent (0.

Identifying molecular signatures in metal-molecule-metal junctions.

Single molecule identification in metal-molecule-metal junctions provides an ultimate probe that opens a new avenue for revolutionary advances in demonstrating single molecule device functions. Inelastic electron tunneling spectroscopy (IETS) is an ultra-sensitive method for probing vibrational characteristics of molecules with atomic resolution. State-of-the-art experiments on the inelastic transport in self-assembled monolayers of organic molecules have demonstrated the utility of the IETS technique to derive structural information concerning molecular conformations and contact configurations.

Dual effects of nobiletin, a citrus polymethoxy flavone, on catecholamine secretion in cultured bovine adrenal medullary cells.

Nobiletin, a compound of polymethoxy flavones found in citrus fruits, possesses a wide range of pharmacological activities. Here we report the effects of nobiletin on catecholamine secretion in cultured bovine adrenal medullary cells. Nobiletin (1.

Salbutamol inhibits lipopolysaccharide-induced inflammatory responses in rat peritoneal macrophages.

Acute and chronic inflammatory diseases are associated with the induction of inducible nitric oxide synthase (iNOS) and inducible heme oxygenase (HO-1). These inducible enzymes are up-regulated in macrophages subjected to inflammatory stimuli and oxidative stress. beta(2)-Adrenoceptor (AR) agonists, which function as bronchial dilators, are widely used for the treatment of asthma and chronic obstructive pulmonary disease (COPD).