Molecular Mechanisms for the Regulation of Insulin-Stimulated Glucose Uptake by Small Guanosine Triphosphatases in Skeletal Muscle and Adipocytes

Insulin is a hormone that regulates the blood glucose level by stimulating various physiological responses in its target tissues. In skeletal muscle and adipose tissue, insulin promotes membrane trafficking of the glucose transporter GLUT4 from GLUT4 storage vesicles to the plasma membrane, thereby facilitating the uptake of glucose from the circulation. Detailed mechanisms underlying insulin-dependent intracellular signal transduction for glucose uptake remain largely unknown. In this article, I give an overview on the recently identified signaling network involving Rab, Ras, and Rho family small guanosine triphosphatases (GTPases) that regulates glucose uptake in insulin-responsive tissues. In particular, the regulatory mechanisms for these small GTPases and the cross-talk between protein kinase and small GTPase cascades are highlighted.     

A QoS-aware routing mechanism for multi-channel multi-interface ad-hoc networks

To accommodate real-time multimedia application while satisfying application QoS requirements in a wireless ad-hoc network, we need QoS control mechanisms. In this paper, we propose a new routing mechanism to support real-time multimedia communication by efficiently utilize the limited wireless network capacity. Our mechanism considers a wireless ad-hoc network composed of nodes equipped with multiple network interfaces to each of which a different wireless channel can be assigned. By embedding information about channel usage in control messages of OLSRv2, each node obtains a view of topology and bandwidth information of the whole network. Based on the obtained information, a source node determines a logical path with the maximum available bandwidth to satisfy application QoS requirements. Through simulation experiments, we confirmed that our proposal effectively routed multimedia packets over a logical path avoiding congested links. As a result, the load on a network is well distributed and the network can accommodate more sessions than QOLSR. We also conducted practical experiments using wireless ad-hoc relay nodes with four network interfaces and verified the practicality of our proposal.     

Synthesis and property study on Eu(III) complexes of modified poly(N-isopropylacrylamide)

Poly(N-isopropylacrylamide) with aromatic end groups (Ar-PNIPAM) were synthesized by atom transfer radical polymerization of N-isopropylacrylamide in isopropanol using phenyl 2-chloropropionate, (4′-phenyl)phenyl 2-chloropropionate, and (2′,6′-diphenyl)phenyl 2-chloropropionate as initiators and CuCl/tris(2-dimethylaminoethyl)amine (Me₆TREN) as a catalytic system. The resulting polymers had narrow polydispersity index of 1.10–1.14 and molecular weights of 3700–4600 g mol⁻¹. Then, novel functional complexes of Ar-PNIPAM, Europium(III) (Eu(III)), and α-Thenoyltrifluoroacetone (TTA) (Ar-PNIPAM/Eu(III)/TTA) with thermosensitive and fluorescent properties were synthesized and characterized by Fourier transform infrared spectra and fluorescence spectroscopy. Metal Eu(III) was not only bonded to oxygen and nitrogen atoms of polymer chain in PNIPAM, but also bonded to TTA. The maximum emission intensity of the complexes at 613 nm was enhanced about 22, 27, 33 times compared with that of the corresponding Eu(III). The lower critical solution temperatures (LCSTs) of Ar-PNIPAM/Eu(III)/TTA were slightly greater compared with that of PNIPAM. Eu(III) complexes had excellent fluorescence performance, the fluorescence spectrum presented characteristic emission of Eu(III) at 613 nm.     

Pathologic features of spinal disorders in patients treated with long-term hemodialysis

STUDY DESIGN: Pathologic features of hemodialysis-associated spinal disorders were evaluated using preoperative radiographic images and histologic findings of the spinal lesions resected during surgery. OBJECTIVES: To investigate the pathology of hemodialysis-related spinal disorders and to determine the role of amyloidosis in the establishment of severe destruction of the spine. SUMMARY OF BACKGROUND DATA: The pathologic events leading to hemodialysis-associated spinal disorders are poorly understood. The distribution of amyloid deposits in the spine also has not been clarified. METHODS: Twenty patients with hemodialysis-associated spinal disorders were investigated regarding pathologic features of neural compression and spinal destruction. Preoperative radiographic images such as plain radiography, tomography, computed tomography, magnetic resonance imaging, and scintigraphy were assessed for the existence of an intracanal mass, hypertrophy of the ligamentum flavum, and destructive changes of the spinal components. Histologic examination also was conducted by light microscopy and scanning electron microscopy to determine the distribution pattern of amyloid deposits in the spinal components. RESULTS: Six patients with no destructive changes in the spine showed spinal canal stenosis. In the cervical spine, a main factor associated with spinal canal stenosis was the presence of intracanal amyloid deposits in three patients. In the lumbar spine, a main factor associated with spinal canal stenosis was hypertrophied ligamentum flavum in three patients. Destructive changes of the facet joints, intervertebral disc, and vertebral body were seen in the other 14 patients. Amyloid deposits were densely distributed at the enthesis of capsular fibers to the bone and in anular tears in the intervertebral discs. Vertebral end plates were destroyed by penetration of amyloid granulation into the vertebral body. Osteoclast activity in the destroyed vertebral bodies was enhanced, with no evidence of new bone formation. CONCLUSIONS: Amyloid deposits played an important role in the progression of spinal destruction and severe instability.     

Transforming growth factor-beta inhibits interferon-gamma secretion by lymphokine-activated killer cells stimulated with tumor cells

The effect of transforming growth factor-beta (TGF-beta) secreted by glioblastoma (T98G) cells on the secretion of interferon-gamma (IFN-gamma) by lymphokine-activated killer (LAK) cells stimulated with tumor cells was investigated in cocultures of LAK and Daudi cells supplemented with T98G culture supernatant, T98G culture supernatant preincubated with anti-TGF-beta 1 and anti-TGF-beta 2 neutralizing antibodies, anti-TGF-beta 1 and anti-TGF-beta 2 antibodies, or natural human TGF-beta 1 or recombinant human TGF-beta 2. LAK cells were incubated with anti-TGF-beta 1 and anti-TGF-beta 2 antibodies, and with T98G cells of which the supernatant contained both active and latent forms of TGF-beta 1 and TGF-beta 2, with or without neutralizing antibodies. Addition of the supernatant from T98G cells to LAK/Daudi culture caused inhibition of IFN-gamma secretion by LAK cells. The inhibition was abolished by pretreatment of the supernatants with anti-TGF-beta antibodies. Addition of TGF-beta 1 and TGF-beta 2 to the LAK/Daudi culture inhibited IFN-gamma secretion by LAK cells in a dose-dependent manner. Addition of anti-TGF-beta antibodies to the LAK culture resulted in increased IFN-gamma secretion. T98G cells failed to stimulate LAK cells to secrete more IFN-gamma. Addition of anti-TGF-beta antibodies to the LAK-T98G culture resulted in increased IFN-gamma secretion by LAK cells. These results suggest that most malignant glioma cells which secrete high levels of TGF-beta can inhibit IFN-gamma secretion by LAK cells even after tumor cell stimulation.     

Is the nitric oxide system involved in genetic hypertension in Dahl rats?

To address this issue, a series of genetic tests were carried out. Linkage studies showed that the inducible nitric oxide synthase (Nos2) locus cosegregated with blood pressure in three F2 populations originated from crosses of Dahl salt-sensitive (S) rats with rats of various normotensive strains. However, the brain nitric oxidase synthase (Nos1) and endothelial nitric oxide synthase (Nos3) loci did not cosegregate with blood pressure in five F2 populations. Thus, only Nos2, but not Nos1 and Nos3, was considered as a candidate gene for being a quantitative trait locus (QTL) for blood pressure in the S rat. To further test this hypothesis, congenic strains were constructed by substituting regions on Chromosome 10 of the S rat with the homologous regions of the Milan normotensive (MNS) rat. Results showed that the chromosome region including Nos2 did not contain a blood pressure QTL. In consequence, Nos2 per se is not supported as a candidate QTL capable of causing a blood pressure difference between the S and MNS rats. Nevertheless, the nitric oxide system appears to be involved secondarily in the regulation of blood pressure in the S rat, as evidenced by physiological data.     

Nonrandomness in protein sequences: evidence for a physically driven stage of evolution?

The sequences, or primary structures, of existing biopolymers--in particular, proteins--are believed to be a product of evolution. Are the sequences random? If not, what is the character of this nonrandomness? To explore the statistics of protein sequences, we use the idea of mapping the sequence onto the trajectory of a random walk, originally proposed by Peng et al. [Peng, C.-K., Buldyrev, S. V., Goldberger, A. L., Havlin, S., Sciortino, F., Simons, M. & Stanley, H. E. (1992) Nature (London) 356, 168-170] in their analysis of DNA sequences. Using three different mappings, corresponding to three basic physical interactions between amino acids, we found pronounced deviations from pure randomness, and these deviations seem directed toward minimization of the energy of the three-dimensional structure. We consider this result as evidence for a physically driven stage of evolution.