bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic variation in rates of antipyrine metabolite formation: a study in uninduced twins.
Authors: Penno M B , Dvorchik B H , Vesell E S
Published: May 2006

Adult, male, unmedicated twins received antipyrine orally under carefully controlled environmental conditions. Relative contributions of genetic and environmental factors to 2-fold interindividual variations in rate constants for formation of the three main antipyrine metabolites were compared. Heritabilities for rate constants for formation of 4-hydroxyantipyrine, N-demethylantipyrine, and 3-hydroxymethylantipyrine were 0.88, 0.85, and 0.70, respectively. These results suggest that each molecular form of cytochrome P-450 that converts antipyrine to a different metabolite exhibits genetically controlled interindividual variations in activity. Unrelated adult male subjects whose environments were also carefully controlled exhibited highly reproducible rate constants for formation of antipyrine metabolites. Because the rate constant for metabolite formation sensitively detects certain variations in the gene product, it should be used in future pharmacogenetic studies on rates of production of multiple metabolites from a single parent drug.
Norepinephrine neuronal uptake binding sites in rat brain membranes labeled with [3H]desipramine.
Authors: Lee C M , Snyder S H
Published: May 2006

Neuronal uptake recognition sites in norepinephrine neurons have been labeled with the antidepressant [3H]desipramine. A high-affinity component of [3H]desipramine binding to rat cerebral cortex membranes is abolished selectively by 6-hydroxydopamine lesions, which destroy central catecholamine neurons. The high-affinity [3H]desipramine binding has a nanomolar affinity constant for desipramine and is inhibited by tricyclic antidepressants with potencies that correlate with their ability to inhibit the neuronal uptake of norepinephrine. [3H]Desipramine binding to the uptake sites is markedly stimulated by sodium, with potassium, lithium, and choline being much less effective. The ability to monitor norepinephrine neuronal uptake "receptors" in simple binding studies should permit a differential analysis of drug influences on the norepinephrine recognition site and the translocation mechanism. The regulation of [3H]desipramine binding by sodium may help clarify how sodium influences neurotransmitter uptake.
Universal energy principle of biological systems and the unity of bioenergetics.
Authors: Green D E , Zande H D
Published: May 2006

Electronic energy (chemical bond energy) is the exclusive source of utilizable energy in biological systems. The release of this energy is mediated enzymically. The energy required to rupture a single covalent or ionic bond is prohibitively high under physiological conditions [in the range of 80-200 kcal/mol (1 kcal = 4.18 kJ)]. By the technique of the pairing of bond rupture (two juxtaposed bonds ruptured simultaneously) and the pairing of bond formation, enzymes can bypass the huge thermodynamic barrier to chemical change inherent in rupture of a single bond and operate within thermal limits. Enzymes accordingly can be conceived of as the energy machines that translate this principle. The principle of this transduction is that the energy required for forming a new covalent bond can fall within thermal limits when the original charged atom partner to the bond is displaced by a substitute charged atom under conditions in which the charge field of the bond remains constant during the substitution. In the transition from classical enzymology to energy coupling, muscular contraction, template-dependent replication, etc., new dimensions and possibilities are added to the basic enzymatic machinery. Specialized molecular devices (membranes, filaments, channels, templates, etc.) have to be introduced to make possible these extensions and permutations of enzymology. But it is demonstrable that the basis pairing principle is fully preserved during any of these modifications or extensions. Long range movement--of an ion, a filament, or a template--is the most important property introduced into classical enzymology in the transition to energy coupling systems.
The dnaN gene codes for the beta subunit of DNA polymerase III holoenzyme of escherichia coli.
Authors: Burgers P M , Kornberg A , Sakakibara Y
Published: May 2006

An Escherichia coli mutant, dnaN59, stops DNA synthesis promptly upon a shift to a high temperature; the wild-type dnaN gene carried in a transducing phage encodes a polypeptide of about 41,000 daltons [Sakakibara, Y. & Mizukami, T. (1980) Mol. Gen. Genet. 178, 541-553; Yuasa, S. & Sakakibara, Y. (1980) Mol. Gen. Genet. 180, 267-273]. We now find that the product of dnaN gene is the beta subunit of DNA polymerase III holoenzyme, the principal DNA synthetic multipolypeptide complex in E. coli. The conclusion is based on the following observations: (i) Extracts from dnaN59 cells were defective in phage phi X174 and G4 DNA synthesis after the mutant cells had been exposed to the increased temperature. (ii) The enzymatic defect was overcome by addition of purified beta subunit but not by other subunits of DNA polymerase III holoenzyme or by other replication proteins required for phi X174 DNA synthesis. (iii) Partially purified beta subunit from the dnaN mutant, unlike that from the wild type, was inactive in reconstituting the holoenzyme when mixed with the other purified subunits. (iv) Increased dosage of the dnaN gene provided by a plasmid carrying the gene raised cellular levels of the beta subunit 5- to 6-fold.
Gene II of phage f1: its functions and its products.
Authors: Dotto G P , Enea V , Zinder N D
Published: May 2006

Plasmids harboring the amino-terminal part of bacteriophage f1 gene II confer to bacterial cells partial resistance to infection with the male-specific bacteriophages f1 and f2. This effect (IP-2 phenotype) is due to the production of large amounts of an approximately 20,000-dalton polypeptide corresponding to the amino-terminal part of gene II protein. These results have allowed the isolation of clones producing functional gene II protein in large amounts. An in vitro assay has been developed to test the enzymatic activity of the gene II protein produced.
Spermidine, an intrinsic component of turnip yellow mosaic virus.
Authors: Cohen S S , Greenberg M L
Published: May 2006

The major polyamine of turnip yellow mosaic virus has been identified as spermidine by gas chromatography and mass spectrometry of the trifluoroacetamido derivative. Very small amounts of putrescine and cadaverine, but not norspermidine, have been detected in the virus. The spermidine contents of numerous virus preparations were in the range 200-700 molecules per virion and were considerably in excess of those of spermine. The RNA and spermidine contents of small amounts of the virus were determined after serological precipitation in purified preparations and in the juice of infected plants. Under conditions of the precipitation or purification from juice by differential centrifugation, only small amounts of exogenous radioactive spermidine and spermine became bound to virus. Although adsorbed radioactive spermidine could be removed almost quantitatively by washing the virus in dilute buffers, only a small part of adsorbed spermine was removed by such treatment. However, greater than 95% of the newly attached spermine was separated from the virus without loss of the original spermidine by sedimentation in buffers containing 0.5 M NaCl or 0.06 M MgCl2. Crystallization of virus in 40% saturated MgSO4 or 7.5% heparin or dialysis did not decrease viral spermidine. Although the virus coat may adsorb small amounts of the polyamines reversibly, the virus is impermeable to exogenous spermidine and spermine and does not exchange or leak internal spermidine. The spermidine present in purified virus is associated with viral RNA at the time of packaging and formation of intact virions.
Knotted DNA from bacteriophage capsids.
Authors: Liu L F , Perkocha L , Calendar R , Wang J C
Published: May 2006

The majority of the DNA prepared from tailless capsids of bacteriophage P2 by the phenol extraction procedure consists of monomeric rings that have their cohesive ends joined. Electron microscopic and ultracentrifugal studies indicate that these molecules have a complex structure that is topologically knotted; they have a more compact appearance and a higher sedimentation coefficient when compared with regular nicked P2 DNA rings. Linearization of these rings by thermal dissociation or repair of the cohesive ends by DNA polymerase I in the presence of all four deoxynucleoside triphosphates gives molecules that are indistinguishable from normal P2 DNA that has been similarly treated. The knotted nature of the majority of P2 head DNA is further supported by analyzing the products when these molecules are treated with ligase and the ligase-treated molecules are subsequently nicked randomly with DNase I. The data are consistent with the notion that, if such a molecule is first converted to a form that contains only one single-chain scission per molecule, strand separation gives a linear strand and a highly knotted single-stranded ring. The results suggest that the DNA packaged in tailless P2 capsids is arranged in a way that leads to the formation of a complex knot when the ends join. In an intact phage particle, the anchoring of one terminus of the DNA to the head-proximal end of the tail [Chattoraj, D. K. & Inman, R. B. (1974) J. Mol. Biol. 87, 11-22] presumably diminishes or prevents this kind of joining. The novel knotted DNA can be used to assay type II DNA topoisomerases that break and rejoin DNA in a double-stranded fashion.
X-ray diffraction of strained muscle fibers in rigor.
Authors: Naylor G R , Podolsky R J
Published: May 2006

The effect of strain on the equatorial x-ray diffraction pattern of glycerinated rabbit psoas fibers was studied in the rigor (ATP free) state. Strains between 30 and 100 A per half sarcomere, measured directly by laser diffraction, did not change the intensity ratio, (10)/ . (11). Because the intensity ratio depends on the distribution of mass within the myofilament lattice, the negative result indicates that strain does not change the angle of attachment of the subfragment 1 (S1) moiety of the myosin molecule to the actin filament. The effect of strain on the ordering of the actin filaments also was considered and judged to be negligible.
Structural and functional alterations in microtubule protein from Chinese hamster ovary cell mutants.
Authors: Keates R A , Sarangi F , Ling V
Published: May 2006

We have examined mutant lines of Chinese hamster ovary cells that have increased resistance to the antimicrotubule drug Colcemid. Analysis of the functional properties of purified microtubule protein indicates that increased tolerance to the drug in vivo is reflected in altered properties of microtubules and tubulin in vitro. In this study, we have examined one series of related mutants and have found different microtubule alterations associated with each selection step. These changes include decreased Colcemid-binding affinity, an altered electrophoretic pattern of tubulin subcomponents, increased resistance to Colcemid inhibition of polymerization in vitro and, in one case, a decreased critical concentration for microtubule assembly. Characterized mutants of the class described here will be useful for probing the regulation of microtubule assembly in vivo.
Insulin immunoreactive sites demonstrated in the Golgi apparatus of pancreatic B cells.
Authors: Ravazzola M , Perrelet A , Roth J , Orci L
Published: May 2006

Insulin immunoreactive sites were localized in the Golgi apparatus of pancreatic B cells by light and electron microscopy. Identification of the Golgi apparatus by immunofluorescence required the prior degranulation of B cells with glibenclamide to reduce the insulin immunostaining due to secretory granules. In such cells, insulin immunofluorescence revealed brightly stained, crescent-shaped strands with form and location super-imposable on that of Golgi complexes seen in thin sections of the same cells. With the electron microscope, the insulin immunoreactive sites revealed by the protein A/gold technique were localized in the cisternae and vesicles of the Golgi apparatus of glibenclamide-treated and control B cells and over maturing and mature secretory granules. The quantitative evaluation of the intensity of the insulin immunoreactive sites in the Golgi apparatus revealed a density of sites 4 times more than cellular background values. The demonstration of insulin immunoreactivity in the Golgi apparatus provides direct evidence for the involvement of this compartment in the transport and maturation of proinsulin into insulin.
Membrane modification differentially affects the binding of the lactogenic hormones human growth hormone and ovine prolactin.
Authors: Bhattacharya A , Vonderhaar B K
Published: May 2006

Human growth hormone (hGH) and ovine prolactin (oPRL) are both lactogenic as defined by their ability to induce milk-protein synthesis in vitro in the presence of insulin and hydrocortisone. At physiological concentrations, both hGH and oPRL have similar dose-response curves in a mouse mammary gland organ culture system. Binding of 125I-labeled hGH (125I-hGH) to lactogenic receptors is competed by both hGH and oPRL, and the competition curves are nearly superimposable. Moreover, solubilized membrane proteins bound with either 125I-hGH or 125I-labeled oPRL (125I-oPRL) show the same sedimentation pattern on sucrose gradients. However, methylation of membrane phospholipids in the presence of the methyl donor S-adenosyl-L-methionine only increases the binding of 125I-hGH. Binding of either 125I-oPRL or 125I-labeled bovine growth hormone (125I-bGH) was unaffected. Addition of concanavalin A (Con A) to the membranes decreased binding of 125I-oPRL to the lactogenic site by 80%, whereas 125I-hGH binding was decreased by only 40%, with the binding of 125I-bGH unaffected. However, both hGH-and oPRL-bound proteins bind to Con A-Sepharose columns to the same extent. These results suggest that although hGH and oPRL bind to the same lactogenic site with similar affinities and elicit similar biological responses, modification of membranes either by phospholipid methylation or by Con A differentially affects the binding of these two hormones.
DNA-mediated gene transfer of beta-aspartylhydroxamate resistance into Chinese hamster ovary cells.
Authors: Andrulis I L , Siminovitch L
Published: May 2006

Cell lines that have high levels of resistance to beta-aspartylhydroxamate and elevated levels of asparagine synthetase activity were selected in two steps from Chinese hamster ovary cells. Resistance to beta-aspartylhydroxmate was transferred into sensitive cells by using total genomic DNA derived from the dominant two-step mutants. The surviving colonies were characterized as transferants on the basis of transfer frequency, degree of resistance to beta-aspartylhydroxamate, increased level of asparagine synthetase activity, expression of the donor form of asparagine synthetase, codominance in hybrids, and instability of the phenotype in the absence of selection.
Functional cooperation of the dnaE and dnaN gene products in Escherichia coli.
Authors: Kuwabara N , Uchida H
Published: May 2006

A system was designed to isolate second-site intergenic suppressors of a thermosensitive mutation of the dnaE gene of Escherichia coli. The dnaE gene codes for the alpha subunit of DNA polymerase III [McHenry, C. S. & Crow, W. (1979) J. Biol. Chem. 254, 1748-1753]. One such suppressor, named sueA77, was finely mapped and found to be located at 82 min on the E. coli chromosome, between dnaA and recF, and within the dnaN gene [Sakakibara, Y. & Mizukami, T. (1980) Mol. Gen. Genet. 178, 541-553]. The dnaN gene codes for the beta subunit of DNA polymerase III holoenzyme [Burgers, P. M. J., Kornberg, A. & Sakakibara, Y. (1981) Proc. Natl. Acad. Sci. USA 78, 5391-5395]. The sueA77 mutation was trans-dominant over its wild-type allele, and it suppressed different thermosensitive mutations of dnaE with different maximal permissive temperature. These properties were interpreted as providing genetic evidence for interaction of the dnaE and dnaN gene products in E. coli.
Mouse immunoglobulin coding sequences for the heavy-chain variable region arose as repeats of the two short building blocks.
Authors: Ohno S , Kato K , Hozumi T , Matsunaga T
Published: May 2006

The coding sequence for the 97-amino-acid-residue-long immunoglobulin heavy-chain variable (VH) regions of the mouse apparently arose as repeats of the two short building blocks. Three of the recognizable copies of the one 21-base-long prototype sequence A-C-T-G-G-A-T-A-T-G-A-C-C-T-G-G-A-G-T-G-G are invariably found to occupy the fixed positions within the 5' half of each VH coding sequence. Interestingly, the first and third copies specify the relatively invariant regions represented by the 7th to 13th and 41st to 47th amino acid residues (the first and second framework regions), whereas the second copy specifies the first hypervariable region (31st to 35th amino acid residues). These copies maintain at least 57.2% (12 out of 21) base sequence homology to the above-noted prototype building block. Base sequences of the other 14- to 15-base-long prototype building block differ from each other by as much as 60% between individual VHS. Yet one of its copies invariably occupies the terminal region of each VH coding sequence, thus specifying the very invariant third framework region. Other copies occupy unfixed positions in the VH and its attendant hydrophobic leader coding sequence as well as in adjacent noncoding sequences. The homology thus revealed between the VH coding sequence and its adjacent noncoding sequences suggests their concordant evolution.
Detection of genes coding for human differentiation markers by their transient expression after DNA transfer.
Authors: Chang L J , Gamble C L , Izaguirre C A , Minden M D , Mak T W , McCulloch E A
Published: May 2006

We have developed an assay for specific genes in DNA based on transient expression. DNA prepared from patients with acute myeloblastic or acute lymphoblastic leukemia or from the continuous leukemic cell line HL60 was transferred to LTA cells; 48-72 hr later, these recipients expressed hemopoietic differentiation markers as detected by monoclonal antibodies against My-1 (granulocyte specific) and OK-T3 (T-cell specific) using immunofluorescence. The efficiency of transfer was dose and time dependent. We found that genes not expressed in the original cells were expressed after transfer by using this assay. Restriction enzyme analysis showed that My-1 was not expressed with DNA that had been incubated before transfer with either HindIII or Sal I but was present after digestion with either EcoRI or BamHI; after digestion of DNA with the same enzymes, OK-T3 expression was observed only in the HindIII-treated DNA. These studies indicate that DNA was transferred; this approach may provide an efficient method for detecting the activity of specific genes in the absence of selection.
Comparison of poly(dG-dC).poly(dG-dC) conformations in oriented films and in solution.
Authors: Pilet J , Leng M
Published: May 2006

The structures of B and Z forms of poly(dG-dC).poly(dG-dC) in oriented hydrated films have been investigated by infrared spectroscopy. First, the infrared linear dichroism spectrum of poly(dG-dC).poly(dG-dC) in B form (high relative humidity and 2 M Na+) was recorded. The spectrum of the Z form was recorded at a lower relative humidity and higher sodium content (4 M). The experimental conditions were similar to those used in x-ray diffraction studies of left-handed poly(dG-dC).poly(dG-dC) fibers. A qualitative agreement was found between the calculated values of the angles characteristic of the orientation of PO-2 groups with respect to the helical axis in the ZI form and the experimental values. The infrared spectra of B and Z form and the experimental values. The infrared spectra of B and Z forms show some significant differences in H2O and 2H2O. The deuteration rates of exchangeable protons involved in hydrogen bonds between guanine and cytosine residues were deduced from the changes in absorbance near 1700 cm-1. In the B form, the exchange half-time is of the order of 20 min. In the Z form, the exchange half-time of some protons is very slow, of the order of 24 hr. Because of the similarity between these values and those previously reported for the high-salt and low-salt form of poly(dG-dC).poly(dG-dC) in solution, we conclude that the high-salt form of poly(dG-dC).poly(dG-dC) in solution belongs to the Z family.
Mechanism of induction of prolactin synthesis in GH cells
Authors: Biswas Debajit K. , Hanes Steven D. , Brennessel Barbara A.
Published: May 2006

Prolactin-specific RNA (RNA
PRL
) in total nuclear RNA and in cytoplasmic poly(A)
+
RNA isolated from GH (rat pituitary) cells was selectively hybridized to immobilized cloned cDNA
PRL
. Agarose gel electrophoresis of the nuclear RNA
PRL
sequences eluted from the nitrocellulose filters revealed several RNA species of approximately 25-30, 18-19, and 12-13 S. Only the 12-13 S RNA species could be detected in the cytoplasmic poly(A)
+
RNA fraction. Comparative analysis of total nuclear RNA of control and thyrotropin-releasing hormone (thyroliberin)-treated cells by the reverse Southern blot technique demonstrated increased levels of all the nuclear RNA
PRL
species in hormone-treated cells. Nuclear and cytoplasmic RNA
PRL
sequences in control and treated cells were quantitated by molecular hybridization to cloned cDNA
PRL
. The 2- to 3-fold stimulation of PRL production by thyrotropin-releasing hormone-treated GH
4
C
1
cells could be correlated to the corresponding increase of nuclear RNA
PRL
sequences. The hybrid strain, which produces 1/5th the amount of PRL that the parent GH
4
C
1
does, had 1/5th the amounts of nuclear RNA
PRL
sequences. Thyrotropin-releasing hormone affected neither prolactin production nor nuclear RNA
PRL
level in 928-9b cells. RNA
PRL
sequences could not be detected either in nuclei or in cytoplasm of prolactin nonproducing F
1
BGH
1
2C
1
cells. However, prolactin production could be induced and RNA
PRL
sequences could be detected in the total nuclear RNA and in cytoplasmic poly(A)
+
RNA fraction after treatment of this GH cell substrain with 5-bromodeoxyuridine. These results demonstrate that differential basal prolactin production and its modulation by thyrotropin-releasing hormone and by 5-bromodeoxyuridine can be correlated to the altered levels of nuclear RNA
PRL
sequences in the three GH cell strains.
Small nuclear RNAs are encoded in the nontranscribed region of ribosomal spacer DNA.
Authors: Reichel R , Monstein H J , Jansen H W , Philipson L , Benecke B J
Published: May 2006

The structure of in vitro synthesized mouse small nuclear RNA transcribed by RNA polymerase I (snPI RNA) was studied by T1 RNase digestion pattern analysis. The patterns of four different snPI RNA species were different from those of the U1 and U2 RNA species. In addition, the four different snPI RNA species, ranging from 130 to 240 nucleotides in length, yielded almost identical patterns. The snPI RNA molecules hybridized to cloned mouse ribosomal DNA containing the nontranscribed spacer DNA and 45S ribosomal precursor RNA molecules did not compete with this hybridization. Southern blot analysis of fragments from the ribosomal DNA confirmed that snPI RNA species exclusively hybridized to sequences corresponding to the so-called nontranscribed ribosomal spacer region.
Allelic and nonallelic homology of a supergene family.
Authors: Ohta T
Published: May 2006

A model to explain the high degree of polymorphism at the major histocompatibility complex (MHC) is described. The model incorporates domain transfer between the different loci in a supergene family by either gene conversion or double unequal crossing-over. Population genetics theory is used to formulate changes in the probabilities of allelic and nonallelic gene identities and equilibrium values are obtained. The observed degree of allelic and nonallelic homology in the complex can be explained by assuming that a domain is converted at a rate of 10(-5) to 10(-6) per generation and reasonable values of other parameters. This rate of domain transfer is compatible with the observed high mutation rate at marker loci in the major histocompatibility complex.
Geometric specificity of alcohol dehydrogenases and its potential for separation of trans and cis isomers of unsaturated aldehydes.
Authors: Klibanov A M , Giannousis P P
Published: May 2006

The geometric specificity of three different alcohol dehydrogenases (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) (from yeast, from horse liver, and from Leuconostoc mesenteroides) in the reduction of trans- and cis-cinnamaldehydes has been investigated. All three enzymes display a remarkable trans specificity: they react with the trans isomer 7 to 647 times faster than with its cis counterpart. Experiments with the enzymatic reduction of 3-phenylpropionaldehyde, a saturated analog of cinnamaldehyde, have revealed that whereas trans-cinnamaldehyde possesses the "right" configuration for the active centers of the alcohol dehydrogenases, the cis isomer apparently does not fit the active centers well. All three alcohol dehydrogenases studied also exhibit a marked trans specificity in the reaction with alpha-methylcinnamaldehyde. The geometric specificity of alcohol dehydrogenases can be used for the production of otherwise hard to synthesize cis isomers of unsaturated aldehydes from their readily available trans counterparts: trans-cinnamaldehyde was irradiated with ultraviolet light (which converted it to a mixture of trans and cis isomers) then treated with NADH and yeast alcohol dehydrogenase (which selectively reduces only trans aldehyde into the alcohol), and finally the mixture of cis-cinnamaldehyde and trans-cinnamyl alcohol was separated easily by preparative column chromatography.
Bacteriophage lambda DNA packaging: scanning for the terminal cohesive end site during packaging.
Authors: Feiss M , Widner W
Published: May 2006

Bacteriophage lambda packages the DNA of the related phage 21 poorly [Hohn, B. (1975) J. Mol. Biol. 98, 93--106]. To understand the nature of the packaging defect, the interaction of the cohesive end site (cos) specific for phage 21 (cos phi 21) with phage lambda terminase has been investigated. The ability of lambda terminase to cleave cos phi 21 was studied in vitro; lambda terminase cleaved cos phi 21 only 1% as well as it cleaved the phage lambda cohesive end site (cos lambda). In vitro packaging experiments showed that the lambda and 21 packaging specificities observed in vivo are also found in vitro. The cos cleavage reaction was modified so that competition experiments could be performed; these experiments showed that cos phi 21 was unable to bind lambda terminase, thus identifying the nature of the defect. Previous work [Feiss, M., Fisher, R. A., Siegele, D. A., Nichols, B. P. & Donelson, J. E. (1979) Virology 92, 56--67] has shown that the base pairs giving lambda or 21 packaging specificity are at the left end of the chromosome, outside the 22-base-pair symmetry region that includes the annealed cohesive ends. Therefore, terminase binding to cos requires interactions with base pairs to the Nu1 side of the cohesive end symmetry segment. The evidence supports the proposition that cos consists of adjacent sites for binding of terminase and for nicking by terminase. Because cos phi 21 can be cut by lambda terminase to terminate DNA packaging, it is proposed that the terminase that binds and nicks at the initial cos site is brought into contact with the terminal cos site by the packaging process. Terminase recognizes and nicks the cohesive end sequence of the terminal cos without requiring the binding site.
Evolution of interference competition by individual, family, and group selection
Authors: Wade Michael J.
Published: May 2006

The necessary conditions for the evolution of social behaviors in a population with three levels of biological organization are derived by using a population genetic model (one locus, two alleles, random mating, discrete generations). Total selection on the behavior, Δ
q
, is partitioned into the sum of three components: (
i
) Δ

q
I

, selection between individuals within families; (
ii
) Δ

q
F

, selection between families within groups; and (
iii
) Δ

q
G

, selection between groups of families. I show that any level of selection can be made to operate in concert with or in opposition to any other, depending upon the fitness effects of the behavior. The implications of the model are discussed in relation to those adaptive explanations of phenotypic traits that generally consider selection to operate only between individuals.
Use of restriction endonucleases for mapping the allele for beta s-globin.
Authors: Wilson J T , Milner P F , Summer M E , Nallaseth F S , Fadel H E , Reindollar R H , McDonough P G , Wilson L B
Published: May 2006

We have reported the direct analysis of the allele for beta 2-globin by using restriction endonuclease Dde I coupled with blot-hybridization analysis. In that report we predicted that a major use of our analysis could be for the prenatal diagnosis of sickle cell anemia. Here we present such an analysis. In addition, this report also describes the use of a new enzyme Mst II, which also distinguish the beta s allele from the normal beta-globin allele. Blot-hybridization analysis with restriction endonuclease Mst II shows the 5' end of the normal beta-globin gene to reside on a fragment of approximately 1.14 kilobases, whereas the 5' end of the beta s-globin gene resides on a fragment of approximately 1.34 kilobases. Because the fragment sizes generated by Mst II are significantly larger than those generated by Dde I, one can easily perform a prenatal diagnosis for sickle cell by standard blot hybridizations onto nitrocellulose filters.
[3H]nitrendipine-labeled calcium channels discriminate inorganic calcium agonists and antagonists.
Authors: Gould R J , Murphy K M , Snyder S H
Published: May 2006

[3H]Nitrendipine binds with high affinity to brain membranes with a drug specificity indicating association with sites mediating the pharmacologic actions of dihydropyridine slow-calcium-channel antagonist drugs. In brain membranes, [3H]nitrendipine binding is absolutely dependent on the presence of calcium ions. Interactions of cation with [3H]nitrendipine binding sites correlate with their physiologic actions at voltage-dependent calcium channels. Ions such as strontium and barium, which mimic calcium physiologically, share the action of calcium in enhancing [3H]nitrendipine binding. Ions such as lanthanum an cobalt, which block the effects of calcium, can inhibit [3H]nitrendipine binding and block the stimulating actions of calcium. The ability to monitor the influence of ions on an agonist-antagonist continuum at [3H]nitrendipine binding sites provides a molecular probe to explore the regulation of cellular function by calcium and other cations.
Structure of crossreactive human histocompatibility antigens HLA-A28 and HLA-A2: possible implications for the generation of HLA polymorphism.
Authors: López de Castro J A , Strominger J L , Strong D M , Orr H T
Published: May 2006

The primary structure of two highly crossreactive human histocompatibility antigens, HLA-A28 and HLA-A2, has been determined to 96% and 90%, respectively, of the papain-solubilized molecules. Their sequences have been compared with the sequence of HLA-B7 and with each other in order to outline the sites of diversity. The overall homology between HLA-B7 and these HLA-A antigens is 86%. A large majority of the differences are located between residues 43 and 195. Within this area, substitutions cluster in at least three segments--residues 65-80, 105-116, and 177-194. HLA-A28 and HLA-A2 show 96% homology. Most of the differences fall within segments 65-74 and 107-116. These results strongly support the suggestion that residues in these segments are integral parts of the alloantigenic determinants of HLA-A28 and HLA-A2. It is further proposed that these three clusters may constitute major, albeit not exclusive, sites of antigenic diversity in human histocompatibility antigens. The nature of the differences among HLA-B7, HLA-A28, and HLA-A2 in the first variable segment suggests that gene conversion might play some role in the generation of HLA polymorphism.
Leukemogenesis by Gross passage A murine leukemia virus: expression of viruses with recombinant env genes in transformed cells.
Authors: Famulari N G , Koehne C F , O'Donnell P V
Published: May 2006

Gross passage A murine leukemia virus (MuLV) derived from extracts of C3Hf/Bi mouse leukemias has been shown to be a virus complex consisting of ecotropic, xenotropic, and recombinant, dualtropic MuLV components. The three virus components were distinguished biochemically by differences in the molecular weights and peptide maps of their primary env gene products synthesized in infected cells in vivo and in vitro. Virus expression was studied in primary leukemias induced in C3Hf/Bi mice by Gross passage A virus extracts and by the individual ecotropic and recombinant MuLV components that were isolated in vitro. Our findings suggest that expression of the recombinant MuLV component of the Gross passage A virus complex is necessary and sufficient for the induction of leukemias in C3Hf/Bi mice. In contrast, induction of leukemias by the ecotropic virus component appears to involve generation of a second virus with characteristics of recombinant, dualtropic MuLV.
On the dynamical basis of the classification of normal galaxies
Authors: Haass J. , Bertin G. , Lin C. C.
Published: May 2006

Some realistic galaxy models have been found to support discrete unstable spiral modes. Here, through the study of the relevant physical mechanisms and an extensive numerical investigation of the properties of the dominant modes in a wide class of galactic equilibria, we show how spiral structures are excited with different morphological features, depending on the properties of the equilibrium model. We identify the basic dynamical parameters and mechanisms and compare the resulting morphology of spiral modes with the actual classification of galaxies. The present study suggests a dynamical basis for the transition among various types and subclasses of normal and barred spiral galaxies.
Identification of a suppressor sequence for DNA replication in the replication origin region of the Bacillus subtilis chromosome.
Authors: Seiki M , Ogasawara N , Yoshikawa H
Published: May 2006

The first replicating fragment of the Bacillus subtilis chromosome, B7, inhibited the replication of the plasmid that carried this fragment. In earlier work using sequential cleavage by Alu I, the suppressor function was located within a 489-base-pair segment. The nucleotide sequence of the entire segment now has been determined. The sequence is characterized by two promoter-like structures and several putative recognition sequences, such as termination signals, 2-fold symmetries, inverted repeats, and repeats. By means of sequential cleavage with exonuclease BAL-31, the essential region for suppression was located in a 200-base-pair region that contains the two promoters with the same orientation. Specific transcription was produced in vitro by using B. subtilis or Escherichia coli RNA polymerases. The transcription was mostly from the second promoter. Elimination of the -35 region of the second promoter dramatically affected both inhibitory activity and in vitro transcription, suggesting that the transcriptional activity of the second promoter is involved in the cis-inhibition of DNA replication. The significance of the suppressor sequence in the region of the replication origin of the B. subtilis chromosome is discussed.
Differential cell cycle phase specificity for neoplastic transformation and mutation to ouabain resistance induced by N-methyl-N'-nitro-N-nitrosoguanidine in synchronized C3H10T 1/2 C18 cells.
Authors: McCormick P J , Bertram J S
Published: May 2006

The transformable mouse embryo fibroblast cell line C3H10T 1/2 C18 has been employed to study the induction by the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) of morphological transformation and mutation to ouabain resistance throughout the cell cycle. Cells were synchronized by means of isoleucine deprivation for 24 hr and initiated DNA synthesis with a high degree of synchrony 7.5 hr after release of the isoleucine block. At various intervals throughout the cell cycle cultures were treated with MNNG at 1.0 microgram/ml and the induction of cytotoxicity, morphological transformation, and ouabain-resistant colonies was determined. All three phenomena exhibited marked cell-cycle phase dependency. Maximal induction of transformation occurred in cultured treated 7.5 hr after release from isoleucine deprivation, when the cells were at the G1/S boundary. In contrast, induction of ouabain-resistant colonies was at a minimum at the time of maximal induction of transformation, and peak induction of ouabain resistance did not occur until 16-18 hr after release from the isoleucine block, when cells were in late S phase. A close correlation was observed between the induction of cytotoxicity and of ouabain-resistant mutants. The results suggest that differences exist in the production or cellular processing of the various early lesions.
Fractal dimensionality of Lévy processes
Authors: Seshadri V. , West Bruce J.
Published: May 2006

We determine the fractal dimensionality
D
of the trajectories of a class of translationally invariant Markov processes. We also provide two simple operational measures to estimate
D
.
Correlations between the activities of DNA polymerase alpha and the glucocorticoid receptor.
Authors: Schmidt T J , Bollum F J , Litwack G
Published: May 2006

Specific inhibitors and anti-DNA polymerase alpha IgG have been utilized to probe for similarities between cytoplasmic rat hepatic glucocorticoid receptors and DNA polymerase alpha [DNA nucleotidyltransferase (DNA-directed), EC 2.7.7.7]. Rifamycin AF/013, an inhibitor of RNA and DNA polymerase activities, significantly inhibited the binding of activated [6,7-3H]-triamcinolone acetonide (TA) receptor complexes to DNA-cellulose. beta-Lapachone, an inhibitor of DNA polymerase alpha and reverse transcriptase activities, inhibited the specific binding of [6,7-3H]TA when preincubated with unbound receptors. Aphidicolin, another DNA polymerase alpha inhibitor, failed to inhibit any of the glucocorticoid-receptor functions tested. Two specific anti-DNA polymerase alpha IgGs interfered with glucocorticoid receptor functions as measured by their ability to inhibit the binding of [6,7-3H]TA to unbound receptors (85% maximal inhibition) and, to a lesser extent, to inhibit the binding of activated [6,7-3H]TA receptor complexes to DNA-cellulose (50% maximal inhibition). The anti-DNA polymerase alpha IgG and beta-lapachone failed to affect the binding of tritiated estradiol, progesterone, or 5 alpha-dihydrotestosterone to their receptors in appropriate rat target tissues or the binding of [1,2-3H]hydrocortisone to serum transcortin. The most obvious interpretation of these data is that cytoplasmic glucocorticoid receptors and DNA polymerase alpha share antigenic determinants. An alternative interpretation is that the polyclonal anti-DNA polymerase alpha antibody contains IgG molecules raised against calf thymus cytoplasmic activated glucocorticoid-receptor complexes that copurified with DNA polymerase alpha used as the antigen. Taken collectively, however, the antibody and inhibitor data suggest a relationship between DNA polymerase alpha and the glucocorticoid receptor.
Flipping of cloned d(pCpG)n.d(pCpG)n DNA sequences from right- to left-handed helical structure by salt, Co(III), or negative supercoiling.
Authors: Peck L J , Nordheim A , Rich A , Wang J C
Published: May 2006

Negative supercoiling of plasmid DNAs containing 24--42 base pairs of alternating d(pCpG) inserts is shown to cause the flipping of the helical hand of the inserts from right to left under physiological conditions. For a negatively supercoiled DNA with a fixed linking number, this flipping reduces its superhelicity and, therefore, is accompanied by a shift of its electrophoretic mobility in agarose gel. Quantitation of the mobility shifts indicates that essentially the whole stretch of contiguous alternating d(pCpG) flips to the left-handed helical form when the negative superhelical density (specific linking difference) is greatest than or equal to 0.03.
Site-directed psoralen crosslinking of DNA.
Authors: Saffran W A , Goldenberg M , Cantor C R
Published: May 2006

A technique has been developed for placing site-specific crosslinks into DNA by using a psoralen derivative containing a sulfhydryl group. Plasmid pBR322 was nicked at the unique BamHI restriction site, and mercurated pyrimidines were introduced by nick-translation. Then the psoralen was specifically directed to this site in the dark through a Hg-S linkage prior to irradiation to form a crosslink. The location of interstrand cross-links was examined by electron microscopy of Pst I-cut molecules and found to be at or near the BamHI site.
Dimer-size DNA circles in a leukemic cell immortalized with the Epstein-Barr virus.
Authors: Gussander E , Adams A
Published: May 2006

The intracellular state of the 30 viral genome equivalents of Epstein-Barr virus (EBV) DNA carried in latent form by the CII cell line, established from a chronic lymphocytic leukemia patient, has been partially characterized. The CII line, which has markers confirming its tumor origin, extends the analysis of the intracellular state of EBV DNA to include other, non-Burkitt lymphoid tumor cells. Monomer-size, free, circular EBV genomes, the major intracellular viral DNA species in other EBV-transformed cells, were absent or present in only minor amounts. Instead, EBV DNA sequences were found associated with a circular DNA form twice the size of the 110 x 10(6) Mr EBV genome. Though circular dimers of mtDNA have been found exclusively in human leukemic lymphocytes, the CII line is similar to normal cells in having only monomer-size mtDNA molecules, which can occur either singly or as catenated forms of two or more interlocking 5-micrometer mtDNA circles.
Environmental influences on the photooxidation of manganese by a zinc porphyrin sensitizer
Authors: Wohlgemuth Roland , Otvos John W. , Calvin Melvin
Published: May 2006

The photosensitized oxidation of a membrane-bound Mn(III) tetrapyridylporphyrin derivative by a Zn tetrapyridylporphyrin derivative, which is confined to the membrane, has been achieved in negatively charged membranes consisting of phosphatidylglycerol or phosphatidic acid. At the same time, the zwitterionic electron acceptor, propylviologen sulfonate (PVS
0
), is reduced in the aqueous phase. The same reaction cannot be obtained with zwitterionic or cationic membranes, nor does this photosensitized reaction take place in a homogeneous solution with Mn(III) tetrapyridylporphyrin and Zn tetrapyridylporphyrin. These results show that the organization of donor, sensitizer, and acceptor at an appropriately selected interface allows reactions that would not occur in homogeneous solutions.
Identification of cloned Y chromosomal DNA sequences from a lampbrush loop of Drosophila hydei.
Authors: Vogt P , Hennig W , Siegmund I
Published: May 2006

By recombinant DNA techniques, a Y chromosomal sequence of Drosophila hydei was isolated. This DNA sequence of 8.93-kilobase length is a member of a family of repetitive sequences located in the short arm of the Y chromosome. Tissue-specific transcripts complementary to the cloned sequence were found in testes RNA. In situ hybridization demonstrated that such transcripts are present in the lampbrush loop pair "nooses" in primary spermatocyte nuclei--a loop pair that is associated with the only fertility gene in the short arm of the Y chromosome.
Characterization of the inactive form of fructose-1,6-bisphosphate aldolase isolated from livers of fasted rabbits.
Authors: Pontremoli S , Melloni E , Michetti M , Salamino F , Sparatore B , Horecker B L
Published: May 2006

The accumulation of an inactive, immunologically crossreactive form of fructose-1,6-bisphosphate aldolase (EC 3.1.3.11) in livers of fasted rabbits has now been related to limited proteolysis at the COOH terminus. The extent of modification of this region of the molecule, determined by analysis of tyrosine residues in the peptides released by digestion with subtilisin, agrees with the observed decrease in the specific activity of the enzyme purified from livers of fasted rabbits. The following evidence supports the conclusion that the modified form is produced in vivo and not during the isolation of the enzyme from the liver homogenates: (i) liver homogenates prepared in isotonic sucrose contained negligible amounts of soluble lysosomal proteinases; (ii) the decreased aldolase activity after fasting was observed in the homogenates and no change in aldolase activity occurred when the homogenates were incubated for 2 hr at 37 degrees C; (iii) the modified enzyme was also isolated from the livers of fasted rabbits when leupeptin was injected intraportally before the animals were sacrificed or when the inhibitor was added to the homogenization solution. On the other hand, homogenization of livers in hypotonic medium resulted in release of lysosomal proteinases and also in decreases in catalytic activity and COOH-terminal modification of liver aldolase, similar to those observed in livers from fasted rabbits. We attribute the changes in activity and structure of aldolase isolated from livers of fasted rabbits to the action in vivo of cathepsin M.
Rapid and transient localization of the leader RNA of vesicular stomatitis virus in the nuclei of infected cells.
Authors: Kurilla M G , Piwnica-Worms H , Keene J D
Published: May 2006

The leader RNA transcript from the 3' end of the genome of vesicular stomatitis virus (VSV) has been detected in both the nucleus and cytoplasm of infected baby hamster kidney (BHK) cells. In the cytoplasm, leader RNA accumulated gradually throughout the infection to about 200 molecules per cell at 6 hr after infection. In the nucleus, however, there was a sharp and rapid increase in the concentration of leader RNA to approximately equal to 300 molecules per cell at about 2 hr after infection that decreased rapidly by 3 hr. This report presents evidence for nuclear localization of transcription products of a (-)-strand RNA virus other than influenza and supports the hypothesis that the leader RNA plays a role in the shutoff of host cell transcription.