ATM: Functions of ATM Kinase and Its Relevance to Hereditary Tumors

Ataxia–telangiectasia mutated (ATM) functions as a key initiator and coordinator of DNA damage and cellular stress responses. ATM signaling pathways contain many downstream targets that regulate multiple important cellular processes, including DNA damage repair, apoptosis, cell cycle arrest, oxidative sensing, and proliferation. Over the past few decades, associations between germline ATM pathogenic variants and cancer risk have been reported, particularly for breast and pancreatic cancers. In addition, given that ATM plays a critical role in repairing double-strand breaks, inhibiting other DNA repair pathways could be a synthetic lethal approach. Based on this rationale, several DNA damage response inhibitors are currently being tested in ATM-deficient cancers. In this review, we discuss the current knowledge related to the structure of the ATM gene, function of ATM kinase, clinical significance of ATM germline pathogenic variants in patients with hereditary cancers, and ongoing efforts to target ATM for the benefit of cancer patients.     

Synthesis of PEG‐functionalized poly(diphenylacetylene)s and their gas permeation properties

The polymerizations of 1‐(3‐methylphenyl)‐2‐(4‐trimethylsilyl)phenylacetylene ( 1a ) and 1‐(4‐methylphenyl)‐2‐(4‐trimethylsilyl)phenylacetylene ( 1b ) were carried out with TaCl₅‐n‐Bu₄Sn to give relatively high‐molecular‐weight polymers ( 2a and 2b ) (M_n > 5 × 10⁵). The obtained polymers were brominated by using benzoyl peroxide and N‐bromosuccinimide first, followed by substitution reaction of three types of polyethylene glycol. When diethylene glycol was used as a reagent on substitution reaction of meta‐substituted polymer, PEG‐functionalized poly(diphenylacetylene) with the highest content of oxyethylene unit [ 4a(2) ] was obtained, and the degree of substitution was 0.60. The degrees of substitution decreased to 0.15 and 0.08 when the polyethylene glycols with higher molecular weights were used. PEG‐substitution reaction to the para‐substituted polymers was difficult to proceed, and hence the degree of substitution was 0.18 even when diethylene glycol was used. The CO₂/N₂ separation factor of PEG‐functionalized polymer [ 4a(2) ] was as large as 28.8, although that of 2a was 7.41. The other PEG‐functionalized polymers also exhibited high CO₂ permselectivity, and their CO₂/N₂ separation factors were over 20. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Photopumped lasing at 1.25 /spl mu/m of GaInNAs-GaAs multiple-quantum-well vertical-cavity surface-emitting lasers

We report room-temperature (RT) continuous-wave (CW) photopumped operation of long-wavelength vertical-cavity surface-emitting lasers (VCSELs) employing a Ga/sub 0.7/In/sub 0.3/N/sub 0.007/As/sub 0.993/-GaAs multiple-quantum-well (MQW) active layer grown directly on a GaAs-AlAs distributed Bragg reflector (DBR). Evidence for laser oscillation includes spectral linewidth narrowing, clamping of spontaneous emission, and a distinct increase in slope efficiency at threshold. By taking advantage of lateral growth rate nonuniformity, we obtained laser emission over an extremely broad 110-nm wavelength range, from 1.146-1.256 /spl mu/m. Equivalent threshold current density over this range was estimated at 3.3-10 kA/cm/sup 2/.     

Ascidian mitochondrial tRNA(Met) possessing unique structural characteristics

Methionine tRNA was purified from muscle mitochondria of the ascidian Halocynthia roretzi and its RNA sequence was determined. Analysis of the nucleotide sequence revealed that unlike most metazoan mitochondrial tRNAs(Met), which have a highly conserved cytidine (C) or C-derivative at the wobble position, the H. roretzi mitochondrial tRNA(Met) possesses 5-carboxymethylaminomethyluridine (cmnm5U) at the first position of the anticodon. This is the first report of a single mitochondrial tRNA(Met) species having uridine (U) or a U-derivative at the wobble position.     

Methyl Anthranilate as an Attractant for Two Thrips Species and the Thrips Parasitoid Ceranisus menes

The role of floral scents in host location by flower-dwelling thrips and a thrips parasitoid was investigated by experiment in the field. The scent of methyl anthranilate significantly increased the catches of Thrips hawaiiensis, Thrips coloratus, and Ceranisus menes, but had no effect on Thrips tabaci. Anisaldehyde increased the catches of T. hawaiiensis and T. tabaci, but had no such effect on T. coloratus and C. menes. Geraniol increased the catches of T. hawaiiensis, but not of T. coloratus, T. tabaci, or C. menes. Seasonal fluctuations of T. hawaiiensis, T. coloratus, and C. menes can be recorded by using methyl anthranilate as a lure for monitoring.     

Metabolic Conversion of C20 Polymethylene-Interrupted Polyunsaturated Fatty Acids to Essential Fatty Acids

Polymethylene-interrupted (PMI)-polyunsaturated fatty acids (PUFA) are fatty acids present largely in gymnosperm. Sciadonic acid (SciA, 20:3 Δ-5,11,14) and juniperonic acid (JA, 20:4 Δ-5,11,14,17) are typical C20 PMI-PUFA with an isolated double bond at Δ5. Previously, we found that SciA and JA are converted to linoleic acid (LNA) and α-linolenic acid (ΑLA), respectively. The conversion process includes chain-shortening step by peroxisomal β-oxidation for elimination a double bond at Δ5, and subsequent chain-elongation step in microsomes. In this study, we examined the substrate specificity of this metabolism in rodent and human cells. Supplementation of SciA, eicosadienoic acid (EDA, 20:2 Δ-11,14) or JA to CHO-K1 cells (wild type) induced an accumulation of LNA, LNA or ALA, respectively, in cellular lipids. These changes were not observed in the peroxisomes-deficient CHO cells, indicating involvement of peroxisomes in the metabolism. Two types of human cells (MKN74 and HepG2) also converted the C20 PMI-PUFA and EDA to the respective essential fatty acids. In contrast, no chain-shortened metabolite of pinolenic acid (18:3 Δ-5,9,12) was detected in any cell lines tested. From these results, C20 PMI-PUFA and EDA, but not C18 PMI-PUFA, are suggested as being effectively converted to essential fatty acids by the fatty acid remodeling system in rodent and human cells.     

Synthesis of poly(<Emphasis Type="Italic">p</Emphasis>-phenyleneethynylene)s bearing oligo-ethylene glycols and their gas permeation properties

1,4-Diiodobenzenes bearing oligo-ethylene glycols [IRC₆H₂IR, R = OCH₂CH₂OCH₃ (1a), O(CH₂CH₂O)₂CH₃ (1b), O(CH₂CH₂O)₃CH₃ (1c)] were polymerized with 1,4-diethynylbenzene in the presence of Pd/Cu catalyst to afford poly(p-phenyleneethynylene)s bearing oligo-ethylene glycols (2a–c), respectively. Polymer 2a was insoluble in any solvents, but the other polymers (2b, 2c) were soluble in CHCl₃. The weight-average molecular weights of 2b and 2c were 5.4 × 10⁴ and 9.6 × 10⁴, respectively, and they gave free-standing membranes by solution-casting method. The densities of membranes of 2b and 2c were 1.26 and 1.22 g/cm³, respectively, and their carbon dioxide permeability coefficients were 12.9 and 13.5 barrers, respectively. The CO₂/N₂ separation factor of membrane of 2b was as large as 33.7. Membrane of 3b, which contains triethylene glycols, exhibited higher CO₂ permselectivity, and the CO₂/N₂ separation factor was 50.0.     

光的游乐场——日本长浜“LEIMONDO”幼儿园

在日本长浜的郊外。有这样一个设计独特的建筑．它矗立在广衰的乡村田野中，拥有着与这里的景色格格不入的轮廓。在祟山峻岭之间安静坚守自己的职责。     

Ejection of Clusters from Liquid Beam Surface by IR Laser Irradiation

A continuous liquid flow of an aqueous solution of phenol (Phe) in a vacuum (a liquid beam) was irradiated with an IR laser at 2.85 μm, which is resonant to the vibrational absorption band of the liquid water. The Phe (H₂O)_N, ejected from the liquid beam surface into the gas phase, was ionized by a UV laser at 270 nm into hydrated phenol cluster ions, Phe⁺ (H₂O)_n (n = 0 − 30), and analyzed by a time-of-flight mass spectrometer. The velocity distributions of the product cluster ions were derived from the spatial distributions measured at different elapsed times after the IR laser irradiation. The results and the analysis show that dense neutral clusters are ejected from surface regions locally heated by the intense IR laser.