MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling

The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well.     

Bacteriophage OP1, lytic for Xanthomonas oryzae pv. oryzae, changes its host range by duplication and deletion of the small domain in the deduced tail fiber gene

The entire genome of bacteriophage OP₁, lytic for Xanthomonas oryzae pv. oryzae causing bacterial leaf blight of rice, and the partial genomes of related phages were sequenced and analyzed. The OP₁ genome comprises double-stranded, 4785-bp long DNA with 51.1% G + C content. Fifty-nine open reading frames (ORFs) were detected. ORF25 had similarity with the tail fiber gene of phages, whose product is related to host specificity. The ORF25 regions were amplified from four host-range mutants (OP_1h, OP_1hC, OP_1h2, and OP_1h2C) by polymerase chain reaction, and their deduced amino acid sequences were compared. Three mutants (OP_1hC, OP_1h2, OP_1h2C) had duplications of a small domain in the N-terminal portion, although there were slight differences in the position of the duplicated sequences. One mutant OP_1h had substituted amino acids in the duplication region. New mutants isolated in the laboratory (OP_1hC and OP_1h2C from OP₁ and OP_1h2) acquired the ability to lyse strain N5874 belonging to phagovar (lysotype) C. However, they rapidly lost this lytic ability when incubated with other phagovars. This loss was always accompanied by a loss of the characteristic repeats, suggesting that the host range of OP₁-related phages changed mainly through duplication and deletion of a small domain in ORF25. The nucleotide sequence data reported are available in the DDBJ/EMBL/GenBank databases under the accession numbers AP008979, AB214312 to AB214316     

The relationship of readily decomposable organic matter of the paddy soil to its colloidal complexes

The soil nitrogen of paddy soil is found to exist in the form of organic and inorganic nitrogen. In general, the content of inorganic nitrogen is so low that it is mainly occupied by organic nitrogen. Such soil organic nitrogen is characterized by large resistance to decomposition by soil microorganisms, and so its mineralization occurs to a small extent in most cases. However, as revealed by M. Shioiri¹⁾ and T. Harada et al. ^2,3), by some appropriate treatment of paddy soil, a part of soil organic nitrogen becomes decomposed by microorganisms and mineralized under flooded condition. Among various treatment, for example, are Presented the followings: (1) air-drying of soil Prior to flooding; (2) raising the soil temperature during the flooded condition; (3) raising the soil reaction (pH 9.0) by addition of weak alkali solution; (4) the addition of neutral salts such as Nafiuoride, Na-phosphate, Na-oxalate etc., which make soil humus peptizable.     

Vesicle endocytosis requires dynamin-dependent GTP hydrolysis at a fast CNS synapse

Molecular dependence of vesicular endocytosis was investigated with capacitance measurements at the calyx of Held terminal in brainstem slices. Intraterminal loading of botulinum toxin E revealed that the rapid capacitance transient implicated as "kiss-and-run" was unrelated to transmitter release. The release-related capacitance change decayed with an endocytotic time constant of 10 to 25 seconds, depending on the magnitude of exocytosis. Presynaptic loading of the nonhydrolyzable guanosine 5'-triphosphate (GTP) analog GTPgS or dynamin-1 proline-rich domain peptide abolished endocytosis. These compounds had no immediate effect on exocytosis, but caused a use-dependent rundown of exocytosis. Thus, the guanosine triphosphatase dynamin-1 is indispensable for vesicle endocytosis at this fast central nervous system (CNS) synapse.     

Morphology and size of embryos recovered from superovulated cows.

A total of 691 normal embryos were recovered from 183 superovulated donor cows on the 5th and 6th days after the first insemination, and were examined for their morphology and size in relation to their developmental stage. There was no significant difference in the thickness of the zona pellucida, the diameter of the cell mass, and the overall diameter of the embryos among zygotes, 2-, 4-, 8- and 16-cell embryos, and morulae. In the blastocyst stage, however, the diameter of the cell mass and the overall embryo diameter were significantly greater and the zona pellucida was significantly thinner than in the earlier-stage embryos. The volume of the blastomere significantly decreased from zygote to morula in proportion to the increase in the number of blastomeres. The volume of the cell mass of 2-cell embryos was decreased by about 30% compared with that of zygotes and no increase in the volume of the cell mass was observed during the progression from 2-cell stage to morula. The diameter of the cell mass and the overall diameter of morulae recovered on the 6th day after the first insemination were significantly greater than those of morulae recovered on the 5th day.     

Enzymatic dehydrogenative polymerization of urushiols in fresh exudates from the lacquer tree, Rhus vernicifera DC

Fresh exudates from the lacquer tree, Rhus vernicifera DC, were extracted with acetone and the solution was chromatographed to isolate monomer, dimer, trimer, and oligomer fractions of urushiols. Constituents of the monomeric and dimeric fractions were then identified by two-dimensional (2D) 1H-13C heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond coherence (HMBC) NMR spectroscopic techniques. The results showed that the monomeric fraction contained 3-[8'Z,11'E,13'Z-pentadecatrienyl]catechol (1), 3-[8'Z,11'Z,14'-pentadecatrienyl]catechol (2), and 3-pentadecanyl]catechol (3), which was verified by HPLC analysis. The dimeric fraction contained 8'-(3' ',4' '-dihydroxy-5' '-alkenyl)phenyl-3-[9'E,11'E,13'Z-pentadecatrienyl]catechol (4), 14'-(3' ',4' '-dihydroxy-5' '-alkenyl)phenyl-3-[8'Z,10'E,12'E-pentadecatrienyl]catechol (5), 2-hydroxyl-3- or -6-alkenylphenyl ethyl ether (6), 14'-(3' ',4' '-dihydroxy-2' '-alkenyl)phenyl-3-[8'Z,10'E,12'E-pentadeca-trienyl]catechol (7), 15'-(2' '-hydroxy-3' '- or -6' '-alkenyl)phenyloxy-3-[8'Z,11'Z,13'E)-pentadecatrienyl]catechol (8), 14'-(2' ',3' '-dihydroxy-4' '-alkenyl)phenyl-3-[8'Z,10'E,12'E-pentadecantrienyl]catechol (9), 1,1',2,2'-tetrahydroxy-6,6'-dialkenyl-4,3'-biphenyl (10), 1,1',2,2'-tetrahydroxy-6,6'-dialkenyl-4,4'-biphenyl (11), 1,1',2,2'-tetrahydroxy-6,6'-dialkenyl-5,4'-biphenyl (12), and 1,2,1'-trihydroxy-6,6'-dialkenyldibenzofuran (13) as constituents. In addition, dimeric ethers and peroxides, such as compounds 14 and 15, were produced by autoxidation of monomeric urushiols in atmospheric air. The possible reaction mechanisms for the dehydrogenative polymerization of urushiols by Rhus laccase present in the fresh raw exudates under the atmospheric oxygen are discussed on the basis of structures identified. This is of primary importance because the use of the urushi exudates as coating materials does not involve organic solvents and is an environmentally friendly process.     

Age and growth of alfonsino Beryx splendens from the Kanto District, central Japan, based on growth increments on otoliths

ABSTRACT:   Age and growth of alfonsino Beryx splendens (Lowe) were studied using counts of presumed daily incremental growth rings on the transverse section of otoliths of fish collected from the Kanto District, central Japan. Microstructural growth increments were observed from the core to the outermost margin of the broadest of approximately 50 branches formed on the surface of an otolith. Of 98 otoliths examined, 46 were readable. The number of increments and fish lengths ranged from 448 (218 mm fork length [FL]) to 3701 (411 mm FL). The ages of these fish were estimated to be 1 year, 2 months and 10 years, 2 months, respectively, assuming that an increment was formed daily. The von Bertalanffy growth equation combined for males and females was expressed as follows: L _t  = 542 {1 −  exp  [−0.133( t  + 2.00)]}, where L _t is fork length (mm) at yearly age t . The results of the present study were compared with those of other researchers who had studied alfonsino from central Japan.     

Correlation of acrylamide generation in thermally processed model systems of asparagine and glucose with color formation, amounts of pyrazines formed, and antioxidative properties of extracts

The relations between the formation of acrylamide and color, pyrazines, or antioxidants in an asparagine/d-glucose browning model system under various conditions were investigated. The highest level of acrylamide was produced in the asparagine/glucose (1:3) system heated at 170 degrees C for 30 min (2629 microg/g asparagine). Color intensity increased with temperature and heating time. The formation of pyrazines increased steadily with an increase of temperature (140-170 degrees C) and heating time (15-60 min). Antioxidant formation varied among the samples heated under different conditions. A clear correlation between formation of acrylamide and browning color was obtained. The formation of acrylamide was linearly correlated with the formation of total pyrazines during the initial stages of the Maillard reaction. No obvious correlation between formation of acrylamide and antioxidants was observed. However, excess amounts of asparagine increased the formation of antioxidants, whereas excess amounts of glucose reduced its formation.