Regulating TERT: Location,location, location

Comment on: Mechanism of dominant-negative telomerase function.

Binh N. Nguyen, Lynne W. Elmore and Shawn E. Holt. Cell Cycle 2009; 8; In press.     

Location,Location, Location: Compartmentalization of Early Events in Leukotriene Biosynthesis

Leukotrienes (LTs), derived from arachidonic acid (AA) released from the membrane by the action of phospholipase A₂, are potent lipid mediators of the inflammatory response. In 1983, Dahlén et al. demonstrated that LTC₄, LTD₄, and LTE₄ mediate antigen-induced constriction of bronchi in tissue obtained from subjects with asthma (Dahlén, S. E., Hansson, G., Hedqvist, P., Björck, T., Granström, E., and Dahlén, B. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 1712–1716). Over the last 25+ years, substantial progress has been made in understanding how LTs exert their effects, and a broader appreciation for the numerous biological processes they mediate has emerged. LT biosynthesis is initiated by the action of 5-lipoxygenase (5-LOX), which catalyzes the transformation of AA to LTA₄ in a two-step reaction. Ca²⁺ targets 5-LOX to the nuclear membrane, where it co-localizes with the 5-LOX-activating protein FLAP and, when present, the downstream enzyme LTC₄ synthase, both transmembrane proteins. Crystal structures of the AA-metabolizing LOXs, LTC₄ synthase, and FLAP combined with biochemical data provide a framework for understanding how subcellular organizations optimize the biosynthesis of these labile hydrophobic signaling compounds, which must navigate pathways that include both membrane and soluble enzymes. The insights these structures afford and the questions they engender are discussed in this minireview.     

Fluid Brain Glycolysis: Limits,Speed, Location,Moonlighting, and the Fates of Glycogen and Lactate

Glycolysis is the core of intermediate metabolism, an ancient pathway discovered in the heydays of classic biochemistry. A hundred years later, it remains a matter of active research, clinical interest and is not devoid of controversy. This review examines topical aspects of glycolysis in the brain, a tissue characterized by an extreme dependence on glucose. The limits of glycolysis are reviewed in terms of flux control by glucose transporters, intercellular lactate shuttling and activity-dependent glycolysis in astrocytes and neurons. What is the site of glycogen mobilization and aerobic glycolysis in brain tissue? We scrutinize the pervasive notions that glycolysis is fast and that catalysis is channeled through supramolecular assemblies. In brain tissue, most glycolytic enzymes are catalytically silent. What then is their function?

     

Timber Procurement and Village Location in the Middle Missouri Subarea

Abstract

Foodstuffs have frequently been regarded as one of the foremost variables when considering population distribution and village location across the landscape. However, other variables may be at least as important as the availability of food. Timber has been noted as a material that is important for fuel and construction purposes, and in some cases can be resource that is crucial for population maintenance in an area.

The importance of timber is examined for the Plains Village populations of the Middle Missouri Subarea, timber succession is examined, and village location in relation to timber resources hypothesized     

Sulfate Assimilation in C(4) Plants: Intercellular and Intracellular Location of ATP Sulfurylase, Cysteine Synthase, and Cystathionine beta-Lyase in Maize Leaves

The activity of ATP sulfurylase, cysteine synthase, and cystathionine β-lyase was measured in crude leaf extracts, bundle sheath strands, and mesophyll and bundle sheath chloroplasts to determine the location of sulfate assimilation of C₄ plant leaves. Almost all the ATP sulfurylase activity was located in the bundle sheath chloroplasts while cysteine synthase and cystathionine β-lyase activity was located, in different proportions, in both chloroplast types.

A new spectrophotometric assay for measuring ATP sulfurylase activity is also described.

     

Location of F1 ATPase-like Genes on the Physical Map of the Bacillus subtilis 168 Chromosome

A water-soluble polysaccharide, FI, extracted from the mycelium of Granoderma tsugae, was fractionated and purified by ion-exchange chromatography, gel filtration, and affinity chromatography. Sixteen polysaccharides obtained were examined for antitumor effects on Sarcoma 180 in mice.

The three active polysaccharides obtained were as follows:

FI₀-a: A glycan-protein complex containing 9.3% protein, and having a hetero-glyco-chain of mannose and xylose.

FI₀-b-α: Molecular weight 10,000, glucan-protein complex containing 25.8% protein. The inhibition ratio was 61.8% against the solid cancer Sarcoma 180/mice; the survival ratio was more than 194% of the control group (100).

FA-1-b-α: Molcular weight 16,000, a complex of glycan: protein = 42:58 w/w, consisting of glucose as a main component, and associated with arabinose, mannose, xylose, and galactose. This had a tumor inhibition ratio of 56% and a survival ratio of more than 182%.

Comparison of active glycan with the fruiting body and mycelium: Among water-soluble polysaccharides of fruiting body, FI₀-a and FA-1, with antitumor activity, were both glucogalactan-protein complexes of molecular weight 10,000, but that of mycelium was a homoglucan protein complex in FI₀-b-α and heteroglucan protein in both FA-l-a and FA-l-b-α. The heteroglucan had a low tumor inhibition ratio, but caused a high survival ratio in mice.     

Location,location, location? No. Catalog number

Once you start to read this Editor’s Corner, you might wonder why I have devoted an entire article, albeit a short one, to this topic. Let me assure you there are reasons. First, I want to announce a new policy for the journal that will affect all research papers. Starting with all papers that are not currently in press, we will no longer be asking for geographical locations of research companies that follow the listing of a reagent. In Materials and Methods the authors typically refer to a reagent and then list the company and its location parenthetically. For example, “…p-nitrophenyl phosphate (Sigma-Aldrich, St. Louis, MO).” Instead, we will require catalog numbers. The reason is that it is now quite easy to find a company using the internet, and in fact you rarely need to know the location because it is rare that you would send a written order. On the other hand, knowing the name of the reagent is not always sufficient to narrow down the precise item. For example, if you search for “p-nitrophenyl phosphate” at the Sigma-Aldrich site, you get seven primary choices and it is not at all obvious which one to choose. When my lab uses p-nitrophenyl phosphate for the Pho8?60 assay, we use item N9389, which narrows it down to a precise reagent. Thus, we will start requiring papers to write “…p-nitrophenyl phosphate (Sigma-Aldrich, N9389).

Second, I think this is actually a useful change, and one that many journals will start to institute once they see it being done here. The old style of listing the city and state is a relic that is no longer relevant. Furthermore, it is not even clear in the current global marketplace if this is particularly helpful. For example, if I am ordering an item from Roche Applied Science, why would anyone care where it is coming from? It is highly unlikely that a researcher in Germany or Japan is going to order from Roche Applied Science that happens to be based in Indianapolis, IN when there are much closer sites in Mannheim, Germany and Tokyo, Japan. So, do not be surprised when you start to see more and more journals adopting this approach, and remember that you saw it here first. Autophagy—the cutting edge.     

Location dependent,intragenic recombination in maize

With the use of chromosome interchanges, the waxy (wx) locus on chromosome 9 has been relocated to various positions in the maize genome. Four wx alleles, wx ^C, wx ^B, wx ⁹⁰, and wx ^H21, were crossed to six chromosome translocation stocks (four with break points proximal to wx and, two distal to wx). Of the 26 possible homozygous translocation heteroallelic combinations, the results of eight are available in this report. In most instances, the frequencies of wx intragenic recombination of the rearranged chromosomes were lower than that of the control. A significant difference in degree of reduction in recombination values is found for different heteroallelic combinations at the same location and in one instance for the same heteroallelic combination at a different chromosome position. The linear order of the 4 wx mutants within the wx cistron is wx ^C-wx ^H21-wx ⁹⁰ (wx ^B). Additional effects from both genetic background and seasonal factors of the different plantings also are observed.Journal Paper No. J-6906 of the Iowa Agriculture and Home Economics Experiment Station, Ames, Iowa. Project No. 1335.     

航空医疗救援体系建设的规划布局与选点定位问题

构建航空医疗救援体系必须要有战略思维才能做好顶层设计,在科学规划、合理布局中解决选点定位问题。从自然环境、服务人口、交通设施、民航存量、产业结构、受灾概率、平战结合、对外交往、发展需求、综合效益等10个方面加以论述,以促进体系规划布局与选点定位更加科学合理。

     

Determination of the Location of Lactone Ring in Surfactin

A single form of exo-type cellulase (Exo I; M_w, 65,000), purified from a Trichoderma viride protease-depressed mutant, HK-75, digested Avicel to cellobiose exowise, and hydrolyzed cellotriose, cellotetraose, and cellopentaose in the strict manner of splitting off by cellobiose units. Exo I, however, hydrolyzed cellohexaose by both cellobiose and cellotriose units.

Exo I was proteolyzed by papain into two fragments; GPExo (M_w, 9,000) and Exo I′ (M_w, 56,000). The GPExo intensively adsorbed onto Avicel but did not hydrolyze it. Exo I′ had nearly identical activity to that of intact Exo I toward cellooligosaccharides but was almost inert to Avicel in digestion and adsorption. Sequence analysis of N-terminal and C-terminal amino acids showed that GPExo was between Gly⁴³⁵ and Leu⁴⁹⁶ and Exo I′ between Glu¹ and Gly⁴³⁴ in Exo I. Exo I therefore consists of two domains, one for adsorption to Avicel, as demonstrated by the Avicel-affinity site, GPExo and the other for the cleavage of glycosidic linkages as demonstrated in Exo 1′.     

Nonparametric,GINI-like Measures of Location and Dispersion

GINI's nonparametric measure of dispersion, defined as the mean of (n/2) pairs of a sample of n measurements, is modified for triplets. That way a GINI-like measure of location G* is defined as the mean of the (n/3) triplet medians, and a GINI-like measure of dispersion is defined as the mean of the (n/3) triplet ranges. G* and g* are less sensitive to outlier measurements than are the corresponding parametric measures, arithmetic mean and standard deviation, in small samples. Applications and application-related problems are discussed.     

A Predictive Model for Site Location in the Alberta Foothills

Abstract

In response to imminent annexation, 44 km2of the lower Simons Valley was subjected to foot survey. The resulting data were used to develop a predictive model for foothills site location, using physiographic zones as the independent variable. Statistical testing shows that the size of the site is related to the physiographic zone it occupies. For habitation sites, it is hypothesized that this variation in size and placement reflects summer and winter occupations, with large summer-winter sites located on low river terraces and congregating in the southern (sheltered) portion of the survey area, while smaller summer sites are spread throughout the survey area. Although no significant relationship was discovered between site type, site size, and the distance of the site from permanent water, the density of the total number of sites was related to this variable.     

Location of two Mn2+ affinity sites in photosystem II detected by pulsed electron–electron double resonance

In this study, we identified two Mn²⁺ sites in apo-Photosystem II (PSII) using the pulsed electron–electron double resonance (PELDOR). A Mn²⁺ ion was bound to apo-PSII on the deactivation of the oxygen-evolving complex. The electron–electron magnetic dipole interaction of the Mn²⁺ to Y_D^· was estimated to be 2.4 MHz. The site was assigned at the position between His332 and Glu189 in the D1 polypeptide, which is close to the Mn1 site in mature PS II. Using recent structures observed under electron microscopes (EM), the location of the Mn²⁺ site on photoactivation was reevaluated. The position between Asp170 and Glu189 in the D1 polypeptide is a good candidate for the initial high-affinity site for photoactivation. Based on a comparison with the PELDOR results, the two EM structures were evaluated.

     

Structure and Location of a Gabaa Receptor Complex in the Central Nervous System

Abstract

GABA-gated chloride channels in the central nervous system contain a regulatory site, the benzodiazepine receptor, through which drugs can modulate the efficiency of GABAergic synaptic transmission and thereby affect the degree of anxiety, muscle tension, vigilance and convulsions. The biochemical analysis of the purified receptor complex with monoclonal antibodies shows a heterooligomeric composition of two glycosylated subunits (α,β). The immunoprecipitated complex contains the binding sites for GABA, benzodiazepines and the convulsant TBPS. The receptor complex was located, immuno-cytochemically, in synapses of brain regions rich in GABAergic nerve terminals.     

Earth,Air, Fire,and Water: Elements of Art

Abstract

Shoshana Zuboff. In the Age of the Smart Machine: The Future of Work and Power. New York: Basic Books, 1988, 468 pp. $11.95 paperback.

George Gilder. Microcosm: The Quantum Revolution in Economics and Technology. New York: Simon &; Schuster, 1989. 426 pp. $19.95 hardcover.

Loren Baritz. The Good Life. New York: Alfred A. Knopf, Inc., 1988. 361 pp. $19.95 hardcover.

Miles Orville. The Real Thing: Imitation and Authority in American Culture, 1880–1940. Chapel Hill: University of North Carolina Press, 1989. 382 pp. $14.95 paperback.

Peter Shaw. The War Against the Intellect. Iowa City: The University of Iowa Press, 1989. 181 pp. $10.95 paperback.

Robert Alter. The Pleasures of Reading in an Ideological Age. New York: Simon &; Schuster, 1989. 250 pp. $18.95 hardcover.

Ian Crofton. A Dictionary of Art Quotations. New York: Macmillan Publishing Company, 1989. $19.95 hardcover.     

Die Beziehungen zwischen Elektrorezeptoren,Elektrischem Organ,Seitenlinienorganen und Nervensystem bei den Mormyridae (Teleostei,Pisces)

Ohne Zusammenfassung

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The interrelations between electroreceptors, electric organ, lateral-line organ and nervous system in Mormyridae (Teleostei, Pisces)

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.

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Der Mathematisch-Naturwissenschaftlichen Fakultät der Universität Tübingen im Jahre 1968 als Habilitationsarbeit vorgelegt.     

ERK Signaling: Duration,Duration, Duration

No Abstract Available

Key Words:

MAP kinase, Growth factor specificity, c-fos, Immediate-early genes, ERK     

Fluorescent Location of Human Colonic Tumour Cells by Means of an Enzyme-Inhibitor Complex

Abstract

We studied the enzymic status of the tumour cell surface protease, guanidinobenzoatase (GB) in frozen sections of a human colonic tumour grown in nude mice and also in human colons. Active enzyme was demonstrated by the binding of a synthetic fluorescent probe for the active centre of guanidinobenzoatase (GB). It was observed that tissue derived inhibitors of GB blocked the binding of this fluorescent probe and that enzyme inhibitor complex formation could be controlled by lowering the pH of the medium with lactic acid. The presence of an inhibitor of GB in the mouse tumour extract was taken advantage of by making two fluorescent derivatives of this inhibitor; both of which located GB on colonic tumour cells in frozen sections of human colon.     

Vorinostat,a possible alternative to metronidazole for the treatment of amebiasis caused by Entamoeba histolytica

Abbreviations SAHA suberoylanilide hydroxamic acid

EhHDAC Histone Deacetylase from Entamoeba histolytica

Rg Radius of gyration

RMSD root-mean-square deviation

RMSF root-mean-square fluctuation

MDS molecular dynamics simulation

VMD Visual Molecular Dynamics

NAMD Nanoscale Molecular Dynamics

PBC periodic boundary conditions

PME Particle Mesh Ewald

3D three-dimensional

Cα alpha carbon

FDA Food and Drug Administration

ns nanoseconds

GPU CUDA Graphics Processing Unit Compute Unified Device Architecture

Communicated by Ramaswamy H. Sarma