Pharmacological studies on a plant lectin,Aloctin A. I. Growth inhibition of mouse methylcholanthrene-induced fibrosarcoma (Meth A) in ascites form by Aloctin A

Summary A glycoprotein isolated fromAloe arborescens Mill markedly inhibited the growth of a syngeneic transplantable fibrosarcoma of mice, Meth A, in ascites form. There is evidence that the inhibition mechanism is host-mediated and not a direct toxic effect on the tumor cell.Acknowledgment. We thank Miss M. Hayama for her technical help.To whom all correspondence should be addressed.     

Glutamate decarboxylase activity in preoptic and hypothalamic nuclei of the rat

Summary Freeze-dried samples were used for the determination of glutamate decarboxylase activity in discrete preoptic and hypothalamic nuclei. The activity showed marked regional variation in distribution.     

T-cell leukemia induced by 1-propyl-1-nitrosourea in Fischer rats

Summary T-cell leukemia was induced at a high rate in female Fischer rats by continuous oral administration of 1-propyl-1-nitrosourea. No association of oncorna viruses were found in the leukemogenesis.The authors are greatly indebted to Professor K. Yokoro of the Department of Pathology, Research Institute for Nuclear Medicine & Biology, for his valuable suggestions. This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan.     

Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA

Innate immune defences are essential for the control of virus infection and are triggered through host recognition of viral macromolecular motifs known as pathogen-associated molecular patterns (PAMPs). Hepatitis C virus (HCV) is an RNA virus that replicates in the liver, and infects 200 million people worldwide. Infection is regulated by hepatic immune defences triggered by the cellular RIG-I helicase. RIG-I binds PAMP RNA and signals interferon regulatory factor 3 activation to induce the expression of interferon-alpha/beta and antiviral/interferon-stimulated genes (ISGs) that limit infection. Here we identify the polyuridine motif of the HCV genome 3' non-translated region and its replication intermediate as the PAMP substrate of RIG-I, and show that this and similar homopolyuridine or homopolyriboadenine motifs present in the genomes of RNA viruses are the chief feature of RIG-I recognition and immune triggering in human and murine cells. 5' terminal triphosphate on the PAMP RNA was necessary but not sufficient for RIG-I binding, which was primarily dependent on homopolymeric ribonucleotide composition, linear structure and length. The HCV PAMP RNA stimulated RIG-I-dependent signalling to induce a hepatic innate immune response in vivo, and triggered interferon and ISG expression to suppress HCV infection in vitro. These results provide a conceptual advance by defining specific homopolymeric RNA motifs within the genome of HCV and other RNA viruses as the PAMP substrate of RIG-I, and demonstrate immunogenic features of the PAMP-RIG-I interaction that could be used as an immune adjuvant for vaccine and immunotherapy approaches.     

Molecular characterization of the melanin-concentrating-hormone receptor.

Orphan G-protein-coupled receptors (GPCRs) are cloned proteins with structural characteristics common to the GPCRs but that bind unidentified ligands. Orphan GPCRs have been used as targets to identify novel transmitter molecules. Here we describe the isolation from brain extracts and the characterization of the natural ligand of a particular orphan GPCR (SLC-1) that is sequentially homologous to the somatostatin receptors. We show that the natural ligand of this receptor is the neuropeptide melanin-concentrating hormone (MCH). MCH is a cyclic peptide that regulates a variety of functions in the mammalian brain, in particular feeding behaviour. We demonstrate that nanomolar concentrations of MCH strongly activate SLC-1-related pathways through G(alpha)i and/or G(alpha)q proteins. We have analysed the tissue localization of the MCH receptor and find that it is expressed in several brain regions, in particular those involved in olfactory learning and reinforcement mechanisms, indicating that therapies targeting the MCH receptor should act on the neuronal regulation of food consumption.     

Rendering Grass Blowing in the Wind with Global Illumination

We have simulated a time varying wind field using the lattice Boltzmann model, and its effect on blades of grass with a simple mass-spring model. We present a global illumination model for multiple scattering of incident sun and sky illumination within the field of grass. We model the grass as a continuous distribution of infinitesimal colored scattering flakes and solve a system of differential equations for the radiance transport. We repeat this for a collection of grass bending directions and amounts, an...     

Real-time spectroscopy of transition states in bacteriorhodopsin during retinal isomerization.

Real-time investigations of the rearrangement of bonds during chemical transformations require femtosecond temporal resolution, so that the atomic vibrations within the reacting molecules can be observed. Following the development of lasers capable of emitting ultrashort laser flashes on this timescale, chemical reactions involving relatively simple molecules have been monitored in detail, revealing the transient existence of intermediate species as reactants are transformed into products. Here we report the direct observation of nuclear motion in a complex biological system, the retinal chromophore of bacteriorhodopsin (bR568), as it undergoes the trans-cis photoisomerization that is fundamental to the vision process. By using visible-light pulses of less than 5 femtosecond in duration, we are able to monitor changes in the vibrational spectra of the transition state and thus show that despite photoexcitation of the anti-bonding molecular orbital involved, isomerization does not occur instantly, but involves transient formation of a so-called 'tumbling state'. Our observations thus agree with growing experimental and ab initio evidence for a three-state photoisomerization model and firmly discount the initially suggested two-state model for this process.     

The paleoclimatic events and cause in the Okinawa Trough during 50 kaBP

Planktonic foraminiferal δ ¹⁸O record for core DGKS9603 from the Okinawa Trough shows a series of climatic fluctuations and sudden cooling events in short time scale during 50 kaBP, which appear to correlate closely to the Younger Dryas and Heinrich events H1-5 recorded in Chinese loess, the South China Sea, the North Atlantic cores and the Greenland ice cores. Three polarity reversal events, correlating to Gothenburg, Mungo and Laschamp events, approximately correspond to Heinrich events H1, H3 and H5 respectively, which could be a cause of global climate changes. The δ ¹⁸O curve of the Okinawa Trough is well associated with the grain size record of the Lijiayuan loess profile in northwestern China and is somewhat different from the climate fluctuations documented in the Greenland ice cores. These correlation results indicate that regional factors play an important role in controlling the climate changes in the East Asia, and the East Asian Monsoon could be the prominent regional controlling factor.