bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Synthesis of a Gene
Authors: Khorana H. G.
Published: October 2006

The method developed for the total synthesis of a given DNA containing biologically specific sequences consists of the following. The DNA in the double-stranded form is carefully divided into short single-stranded segments with suitable overlaps in the complementary strands. All the segments are chemically synthesized starting with protected nucleosides and mononucleotides. The 5′-OH ends of the appropriate oligonucleotides are then phosphorylated with the use of [γ-
32
P]ATP and polynucleotide kinase. A few to several neighboring oligonucleotides are then allowed to form bihelical complexes in aqueous solution, and the latter are joined end to end by polynucleotide ligase to form covalently linked duplexes. Subsequent head-to-tail joining of the short duplexes leads to the total DNA. The methods are described for the construction of a biologically functional suppressor transfer RNA gene. The total work involved (i) the synthesis of a 126-nucleotide-long bihelical DNA corresponding to a known precursor to the tyrosine suppressor transfer RNA, (ii) the sequencing of the promoter region and the distal region adjoining the C-C-A end, which contained a signal for the processing of the RNA transcript, (iii) total synthesis of the 207 base-pair-long DNA, which included the control elements, as well as the Eco R1 restriction endonuclease specific sequences at the two ends, and (iv) full characterization by transcription in vitro and amber suppressor activity in vivo of the synthetic gene.
A Nerve Growth Factor-Induced Gene Encodes a Possible Transcriptional Regulatory Factor
Authors: Milbrandt Jeffrey
Published: October 2006

Nerve growth factor (NGF) is a trophic agent that promotes the outgrowth of nerve fibers from sympathetic and sensory ganglia. The neuronal differentiation stimulated by this hormone was examined in the NGF-responsive cell line PC12. Differential hybridization was used to screen a complementary DNA library constructed from PC12 cells treated with NGF and cycloheximide. One of the complementary DNA clones that was rapidly induced by NGF was found to have a nucleotide sequence that predicts a 54-kilodalton protein with homology to transcriptional regulatory proteins. This clone, NGFI-A, contains three tandemly repeated copies of the 28- to 30-amino acid "zinc finger" domain present in
Xenopus laevis
TFIIIA and other DNA-binding proteins. It also contains another highly conserved unit of eight amino acids that is repeated at least 11 times. The NGFI-A gene is expressed at relatively high levels in the brain, lung, and superior cervical ganglion of the adult rat.
Mutations in the First Exon Are Associated with Altered Transcription of c-
myc
in Burkitt Lymphoma
Authors: Cesarman Ethel , Dalla-Favera Riccardo , Bentley David , Groudine Mark
Published: October 2006

The c-
myc
proto-oncogene is involved in chromosomal translocations that are specifically and consistently found in Burkitt lymphoma. Although these translocations are thought to lead to a deregulation of c-
myc
expression, the structural and functional basis of this phenomenon has not been identified. Mutations in a specific region spanning approximately 70 base pairs and located at the 3′ border of the first exon of translocated c-
myc
alleles were consistently detected in Burkitt lymphoma cells carrying classic (8:14) as well as variant (8:22 and 2:8) translocations. These structural alterations were accompanied by an altered pattern of c-
myc
transcription, namely, the removal of a block to transcriptional elongation that has been mapped to the same region. Thus, specific c-
myc
mutations leading to the alleviation of this block to transcriptional elongation may represent a general mechanism causing c-
myc
activation in Burkitt lymphoma.
Tumor Cell Rejection Through Terminal Cell Differentiation
Authors: Jimenez Joaquin J. , Yunis Adel A.
Published: October 2006

Leukemic cells cultured in the presence of various conditioned media differentiate into macrophages. This finding suggested that the maintenance of undifferentiated state and self-renewal in vivo may be related to the inability of the host to generate an appropriate level of differentiation factor (DF). Evidence for this hypothesis was derived from experiments in vitro and in vivo with myeloid leukemia of rat. The following results were obtained: (i) in vitro, the percentage of cell differentiation at a fixed concentration of DF was inversely related to the concentration of cells; (ii) leukemic cell inoculates that were lethal to 7-day-old rats were rejected by 21-day-old rats; (iii) leukemic cells in diffusion chambers underwent differentiation in 21-day-old rats but not in 7-day-old rats; (iv) organs from 21-day-old rats contained more DF activity than those of 7-day-old rats; (v) treatment of rats with DF in diffusion chambers resulted in leukemic cell differentiation inside the chamber; and (vi) the development of leukemia in 7-day-old rats was aborted by treatment with DF. These results show that the differentiation of rat leukemia cells requires the appropriate level of DF. The proliferation of transplanted leukemia cells in 7-day-old rats goes unchecked because of inadequate generation of DF. Conversely, in the 21-day-old rats, rejection is accomplished by differentiation of the transplanted cells.
Cytosolic Calcium During Contraction of Isolated Mammalian Gastric Muscle Cells
Authors: Bitar K. N. , Bradford P. , Putney J. W. , Makhlouf G. M.
Published: October 2006

During activation of visceral smooth muscle there is an increase in cytosolic-free calcium, but the source (intracellular calcium release or calcium influx), kinetics, and stoichiometry of this increase have not been determined. Here, the fluorescent indicator, quin2-acetoxymethyl ester, was used to measure directly cytosolic-free calcium during contraction of isolated stomach muscle cells induced by the two neuropeptides cholecystokinin-octapeptide and Met-enkephalin as well as acetylcholine. An increase in cytosolic-free calcium was seen that was (i) dependent on the concentration of contractile agonist, (ii) derived from intracellular sources (that is, not significantly affected by removal of ambient calcium or addition of a calcium channel blocker), and (iii) kinetically and stoichiometrically related to net calcium efflux and contraction. In contrast, the increase in cytosolic-free calcium induced by depolarizing concentrations of potassium was caused by influx of calcium through voltage-dependent calcium channels.
Oxytocin Secretion in Response to Cholecystokinin and Food: Differentiation of Nausea from Satiety
Authors: Verbalis Joseph G. , McCann Monica J. , McHale Colleen M. , Stricker Edward M.
Published: October 2006

Administration of cholecystokinin (CCK) to rats caused a dose-dependent increase in plasma levels of the neurohypophyseal hormone oxytocin (OT). The OT secretion was comparable to that found in response to nausea-producing chemical agents that cause learned taste aversions. The effect of CCK on OT secretion was blunted after gastric vagotomy, as was the inhibition of food intake induced by CCK. Food ingestion also led to elevated plasma OT in rats, but CCK and aversive agents caused even greater OT stimulation. Thus, after administration of large doses of CCK, vagally mediated activation of central nausea pathways seems to be predominantly responsible for the subsequent decrease in food intake. Despite their dissimilar affective states, both nausea and satiety may activate a common hypothalamic oxytocinergic pathway that controls the inhibition of ingestion.
Laser-Induced Alteration of Collagen Substructure Allows Microsurgical Tissue Welding
Authors: Schober R. , Ulrich F. , Sander T. , Dürselen H. , Hessel S.
Published: October 2006

Tissue welding is a potentially important biomedical application of laser technology. The structural alterations basic to this phenomenon were studied in experimental repair of lesions of the rat carotid artery and sciatic nerve. A modified neodymium-doped yttrium-aluminum-garnet laser operating at a wavelength of 1.319 micrometers was used in conjunction with conventional suture techniques. Histological and fine-structural analysis revealed a homogenizing change in collagen with interdigitation of altered individual fibrils that appeared to be the structural basis of the welding effect.
A Synthetic Peptide from Fibronectin Inhibits Experimental Metastasis of Murine Melanoma Cells
Authors: Humphries Martin J. , Olden Kenneth , Yamada Kenneth M.
Published: October 2006

Adhesive interactions between cells and the extracellular matrix occur at several stages of metastasis. Such interactions might be inhibited by synthetic peptide probes derived from the cell-binding regions of matrix molecules. Gly-Arg-Gly-Asp-Ser (GRGDS) is a pentapeptide sequence that appears to be critical for cell interaction with fibronectin. Coinjection of GRGDS with B16-F10 murine melanoma cells dramatically inhibited the formation of lung colonies in C57BL/6 mice. Two closely related control peptides, in which specific amino acids within the GRGDS sequence were transposed or substituted, displayed little or no activity. Inhibition by GRGDS was dose-dependent, noncytotoxic, and did not result from an impairment of cellular tumorigenicity. GRGDS may function by inhibiting tumor cell retention in the lung since radiolabeled B16-F10 tumor cells injected with the peptide were lost at a substantially greater rate than control cells.
Replication of the B19 Parvovirus in Human Bone Marrow Cell Cultures
Authors: Ozawa Keiya , Kurtzman Gary , Young Neal
Published: October 2006

The B19 parvovirus is responsible for at least three human diseases. The virus was successfully propagated in suspension cultures of human erythroid bone marrow from patients with hemolytic anemias; release of newly synthesized virus into the supernatants of infected cultures was observed. This culture system allowed study at a molecular level of events associated with the B19 life cycle. The B19 parvovirus replicated through high molecular weight intermediate forms, linked through a terminal hairpin structure. B19 replication in vitro was highly dependent on the erythropoietic content of cultures and on addition of the hormone erythropoietin.
The Effects of Ivermectin on Transmission of
Onchocerca volvulus
Authors: Cupp E. W. , Bernardo M. J. , Kiszewski A. E. , Collins R. C. , Taylor H. R. , Aziz M. A. , Greene B. M.
Published: October 2006

Ivermectin, given to onchocerciasis patients as a single oral dose of 200 micrograms per kilogram of body weight, substantially reduced the uptake of
Onchocerca volvulus
microfilariae by
Simulium yahense
, an efficient black fly vector of the parasite in the tropical rain forests of West Africa. Three months after treatment, patients given ivermectin infected flies at a significantly lower rate than those who had received diethylcarbamazine or placebo, thereby reducing the number of developing larvae in the vector population. This diminished rate of infectiousness was also evident 6 months after treatment. These results strongly suggest that ivermectin could be effective in interrupting transmission of
Onchocerca volvulus
for epidemiologically important periods of time.
Multiple, Distinct Forms of Bovine and Human Protein Kinase C Suggest Diversity in Cellular Signaling Pathways
Authors: Coussens Lisa , Parker Peter J. , Rhee Lucy , Yang-Feng Teresa L. , Chen Ellson , Waterfield Michael D. , Francke Uta , Ullrich Axel
Published: October 2006

A new family of protein kinase C-related genes has been identified in bovine, human, and rat genomes. The alpha-, beta-, and gamma-type protein kinase sequences are highly homologous, include a kinase domain, and potential calcium-binding sites, and they contain interspersed variable regions. The corresponding genes are located on distinct human chromosomes; the possibility of even greater genetic complexity of this gene family is suggested by Northern and Southern hybridization analyses.
Central Projections of Identified, Unmyelinated (C) Afferent Fibers Innervating Mammalian Skin
Authors: Sugiura Y. , Lee C. L. , Perl E. R.
Published: October 2006

Unmyelinated (C) fibers are the most numerous sensory elements of mammalian peripheral nerve and comprise many of those responsible for initiating pain and temperature reactions; however, direct evidence has been lacking as to where and how these fibers terminate in the central nervous system. A plant lectin (
Phaseolus vulgaris
leukoagglutinin) was applied intracellularly by iontophoresis as an immunocytochemical marker. This permitted visualization of the central terminations of cutaneous C sensory fibers that had been identified by the nature of stimuli that excited them. The central branch of C-fiber units arborized and terminated mainly in the superficial layers of the spinal dorsal horn in defined patterns that related to their functional attributes. Thus, the superficial dorsal horn seems to act as a processing station for signals from fine sensory fibers.
Loops in Globular Proteins: A Novel Category of Secondary Structure
Authors: Leszczynski Jacquelyn F. , Rose George D.
Published: October 2006

The protein loop, a novel category of nonregular secondary structure, is a segment of contiguous polypeptide chain that traces a "loop-shaped" path in three-dimensional space; the main chain of an idealized loop resembles a Greek omega (ω). A systematic study was made of 67 proteins of known structure revealing 270 omega loops. Although such loops are typically regarded as "random coil," they are, in fact, highly compact substructures and may also be independent folding units. Loops are almost invariably situated at the protein surface where they are poised to assume important roles in molecular function and biological recognition. They are often observed to be modules of evolutionary exchange and are also natural candidates for bioengineering studies.
Selective Chemical Catalysis by an Antibody
Authors: Pollack Scott J. , Jacobs Jeffrey W. , Schultz Peter G.
Published: October 2006

The immunoglobulin MOPC167, which binds the transition state analog
p
-nitrophenylphosphorylcholine with high affinity, catalyzed the hydrolysis of the corresponding carbonate 1. MOPC167 catalysis displayed saturation kinetics with catalytic constant (
k
cat
) = 0.4 min-1 and Michaelis constant (
K
m
) = 208 μ
M
, showed substrate specificity, and was inhibited by
p
-nitrophenylphosphorylcholine. The rate of the reaction was first order in hydroxide ion concentration between
p
H 6.0 and 8.0. The lower limit for the rate of acceleration of hydrolysis by the antibody above the uncatalyzed reaction was 770. This study begins to define the rules for the generation of catalytic antibodies.
Structures of Two Thermolysin-Inhibitor Complexes That Differ by a Single Hydrogen Bond
Authors: Tronrud Dale E. , Holden Hazel M. , Matthews Brian W.
Published: October 2006

The mode of binding to thermolysin of the ester analog Cbz-Gly
P
-(O)-Leu-Leu has been determined by x-ray crystallography and shown to be virtually identical (maximum difference 0.2 angstrom) with the corresponding peptide analog Cbz-Gly
P
-(NH)-Leu-Leu. The two inhibitors provide a matched pair of enzyme-inhibitor complexes that differ by 4.1 kilocalories per mole in intrinsic binding energy but are essentially identical except for the presence or absence of a specific hydrogen bond.
A G1 Glycoprotein Epitope of La Crosse Virus: a Determinant of Infection of
Aedes triseriatus
Authors: Sundin Daniel R. , Beaty Barry J. , Nathanson Neal , Gonzalez-Scarano Francisco
Published: October 2006

Arthropod-borne viruses (arboviruses) have specific vector-vertebrate host cycles in nature. The molecular basis of restriction of virus replication to a very limited number of vector species is unknown, but the present study suggests that viral attachment proteins are important determinants of vector-virus interactions. The principal vector of La Crosse (LAC) virus is the mosquito
Aedes triseriatus
, and LAC virus efficiently infects the mosquito when ingested. However, a variant (V22) of LAC virus, which was selected by growing the virus in the presence of a monoclonal antibody, was markedly restricted in its ability to infect
Ae. triseriatus
when it was ingested. Only 15% of the mosquitoes that ingested V22 became infected and 5% of these developed disseminated infections. In contrast, 89% of the mosquitoes that ingested LAC became infected and 74% developed disseminated infections. When V22 was passed three times in mosquitoes by feeding, a revertant virus, V22M3, was obtained that infected 85% of
Ae. triseriatus
ingesting this virus. In addition, V22M3 regained the antigenic phenotype and fusion capability of the parent LAC virus. These results suggest that the specificity of LAC virus-vector interactions is markedly influenced by the efficiency of the fusion function of the G1 envelope glycoprotein operating at the midgut level in the arthropod vector.
Somatostatin Cell Processes as Pathways for Paracrine Secretion
Authors: Larsson Lars-Inge , Goltermann Nils , de Magistris Laura , Rehfeld Jens F. , Schwartz Thue W.
Published: October 2006

Somatostatin is produced by gastrointestinal endocrine cells that have long, nonluminal, cytoplasmic processes. Such processes terminate on other cell types, including gastrin-producing and hydrochloric acid-producing cells, whose functions are profoundly affected by somatostatin. The findings suggest that somatostatin cells control the functions of other cells through local release of the peptide by way of cytoplasmic processes. Also, certain other types of gastrointestinal endocrine cells have similar cytoplasmic prolongations, which may have analogous local (paracrine) regulatory functions.
Mechanisms of Antibody Binding to a Protein
Authors: Getzoff Elizabeth D. , Geysen H. Mario , Rodda Stuart J. , Alexander Hannah , Tainer John A. , Lerner Richard A.
Published: October 2006

The mechanisms of antibody binding to a protein were studied by an analysis of specific amino acid residues critical to nine antigenic sites on myohemerythrin. Rabbit antisera to the whole protein were assayed for binding to more than 1500 distinct peptide analogs differing from the protein sequence by single amino acid replacements. The results, combined with information from the three-dimensional crystallographic structure, were used to evaluate probable mechanisms of antibody binding at individual sites. The data from all sites examined indicate that initial binding to solvent-exposed amino acid residues may promote local side-chain displacements and thereby allow the participation of other, previously buried, residues.
Human Retinoblastoma Susceptibility Gene: Cloning, Identification, and Sequence
Authors: Lee Wen-Hwa , Bookstein Robert , Hong Frank , Young Lih-Jiuan , Shew Jin-Yuh , Lee Eva Y.-H. P.
Published: October 2006

Recent evidence indicates the existence of a genetic locus in chromosome region 13q14 that confers susceptibility to retinoblastoma, a cancer of the eye in children. A gene encoding a messenger RNA (mRNA) of 4.6 kilobases (kb), located in the proximity of esterase D, was identified as the retinoblastoma susceptibility (RB) gene on the basis of chromosomal location, homozygous deletion, and tumor-specific alterations in expression. Transcription of this gene was abnormal in six of six retinoblastomas examined: in two tumors, RB mRNA was not detectable, while four others expressed variable quantities of RB mRNA with decreased molecular size of about 4.0 kb. In contrast, full-length RB mRNA was present in human fetal retina and placenta, and in other tumors such as neuroblastoma and medulloblastoma. DNA from retinoblastoma cells had a homozygous gene deletion in one case and hemizygous deletion in another case, while the remainder were not grossly different from normal human control DNA. The gene contains at least 12 exons distributed in a region of over 100 kb. Sequence analysis of complementary DNA clones yielded a single long open reading frame that could encode a hypothetical protein of 816 amino acids. A computer-assisted search of a protein sequence database revealed no closely related proteins. Features of the predicted amino acid sequence include potential metal-binding domains similar to those found in nucleic acid-binding proteins. These results provide a framework for further study of recessive genetic mechanisms in human cancers.
Molecular Cloning of Complementary DNA for the Alpha Subunit of the G Protein that Stimulates Adenylate Cyclase
Authors: Harris Bruce A. , Robishaw Janet D. , Mumby Susanne M. , Gilman Alfred G.
Published: October 2006

A complementary DNA clone encoding the α subunit of the adenylate cyclase stimulatory G protein (G
s
) was isolated and identified. A bovine brain complementary DNA library was screened with an oligonucleotide probe derived from amino acid sequence common to known G proteins. The only clone that was obtained with this probe has a complementary DNA insert of approximately 1670 base pairs. An antibody to a peptide synthesized according to deduced amino acid sequence reacts specifically with the α subunit of G
s
. In addition, RNA that hybridizes with probes made from the clone is detected in wild-type S49 cells; however, cyc
-
S49 cells, which are deficient in G
sα
activity, are devoid of this messenger RNA.
Heterogeneity of Vertebrate Luteinizing Hormone-Releasing Hormone
Authors: King J. A. , Millar R. P.
Published: October 2006

Radioimmunoassay and chromatography analyses of hypothalamic luteinizing hormone-releasing hormone (LHRH) have demonstrated the presence of LHRH-like immunoreactive peptides in a wide range of vertebrates. Contrary to previous reports, the molecule differs in various vertebrates. Avian, reptilian, and teleostean LHRH's are chemically distinct from the mammalian peptide but are in themselves indistinguishable. However, amphibian LHRH appears to be identical to the mammalian peptide. These findings have interesting evolutionary implications.
Control of Cytochrome P
1
-450 Gene Expression by Dioxin
Authors: Jones Phillip B. C. , Galeazzi Donna R. , Fisher Joan M. , Whitlock James P.
Published: October 2006

The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may produce its effects by altering gene expression in susceptible cells. In mouse hepatoma cells, TCDD induces the transcription of the cytochrome P
1
-450 gene, whose product, aryl hydrocarbon hydroxylase, contributes both to the detoxification and to the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons. A DNA fragment containing sequences flanking the 5′ end of the cytochrome P
1
-450 gene was isolated and analyzed. This DNA fragment contains a cis-acting control element with at least three functional domains: a putative promoter, an inhibitory domain upstream from the promoter that blocks its function, and a TCDD-responsive domain still farther (1265 to 1535 base pairs) upstream of the promoter. These findings, together with results from earlier studies, imply that transcription of the cytochrome P
1
-450 gene is under both positive and negative control by at least two
trans
-acting regulatory factors.
Specific Expression of Hepatitis B Surface Antigen (HBsAg) in Transgenic Mice
Authors: Babinet C. , Farza H. , Morello D. , Hadchouel M. , Pourcel C.
Published: October 2006

Two transgenic mice were obtained that contain in their chromosomes the complete hepatitis B virus (HBV) genome except for the core gene. These mice secrete particles of HBV surface antigen (HBsAg) in the serum. In one mouse, HBV DNA sequences that had integrated at two different sites were shown to segregate independently in the first filial generation (F1) and only one of the sequences allowed expression of the surface antigen. Among these animals the males produced five to ten times more HBsAg than the females. A 2.1-kilobase messenger RNA species comigrating with the major surface gene messenger RNA is expressed specifically in the liver in the two original mice. The results suggest that the HBV sequences introduced into the mice are able to confer a tissue-specific expression to the S gene. In addition, the HBV transgenic mice represent a new model for the chronic carrier state of hepatitis B virus infection.
Melatonin: A Coordinating Signal for Mammalian Reproduction?
Authors: Tamarkin Lawrence , Baird Curtis J. , Almeida O. F. X.
Published: October 2006

There is a daily rhythm in the production of the pineal hormone melatonin in all mammalian species. Production is stimulated by darkness and inhibited by light. This provides a signal reflecting the changing environmental lighting cycle. In seasonally breeding mammals that use changes in the photoperiod to time their reproductive cycles, temporal signals to the reproductive system are controlled by the daily rhythm in melatonin production.
Cyclosporin A Binding to Calmodulin: A Possible Site of Action on T Lymphocytes
Authors: Colombani Paul M. , Robb Adelaide , Hess Allan D.
Published: October 2006

Cyclosporin A, a potent immunosuppressive agent, has been widely used to treat patients with solid organ transplants. Although its precise mechanism of action is unknown, it appears to inhibit subsets of T lymphocytes at an early stage in cell activation. Fluorescent, fully active derivatives of cyclosporin A and calmodulin, a protein that binds calcium and is therefore essential to normal cell function, were utilized to demonstrate that cyclosporin A binds to calmodulin. Flow cytometry showed that the calmodulin inhibitors R24571 and W-7 competitively inhibited binding of cyclosporin A to cloned T lymphocytes. Cyclosporin A inhibited the calmodulin-dependent activation of phosphodiesterase in a dose-dependent manner. Binding of cyclosporin A to calmodulin may prevent the latter's role in the activation of the second messengers and enzymes required for effective cell proliferation and function in the immune response.
Thyrotropin-Releasing Hormone Induces Rhythmic Bursting in Neurons of the Nucleus Tractus Solitarius
Authors: Dekin Michael S. , Richerson George B. , Getting Peter A.
Published: October 2006

The nucleus tractus solitarius (NTS) contains neurons that are part of the central neuronal network controlling rhythmic breathing movements in mammals. Nerve terminals within the NTS show immunoreactivity to thyrotropin-releasing hormone (TRH), a neuropeptide that has potent stimulatory effects on respiration. By means of a brainstem slice preparation in vitro, TRH induced rhythmic bursting in neurons in the respiratory division of the NTS. The frequency of bursting was voltage-dependent and could be reset by short depolarizing current pulses. In the presence of tetrodotoxin, TRH produced rhythmic oscillations in membrane potential whose frequency was also voltage-dependent. These observations suggest that TRH modulates the membrane excitability of NTS neurons and allows them to express endogenous bursting activity.
Cell Interactions in Myxobacterial Growth and Development
Authors: Dworkin Martin , Kaiser Dale
Published: October 2006

During their complex life cycle, myxobacteria manifest a number of cell interactions. These include contact-mediated interactions as well as those mediated by soluble extracellular signals. Some of these interactions are well-defined; in addition, the tools for molecular and genetic analysis of these interactions in
Myxococcus xanthus
are now available.
Evolution of Mechanisms Controlling Mating Behavior
Authors: Crews David , Moore Michael C.
Published: October 2006

The proximate mechanisms underlying mating behavior in naturally occurring species can be fundamentally different from those in more commonly studied laboratory and domesticated forms. In naturally occurring species, reproductive strategies are much more diverse, and mechanisms controlling behavior are correspondingly diverse. A variety of hormonal, environmental, and social cues can be used to activate mating behavior. Which cues are used by particular species depends on differences in environmental and physiological constraints imposed by particular reproductive strategies. Study of this diversity of mechanisms promises to identify specific selective forces that have shaped their evolution. This evolutionary perspective leads to widely applicable generalizations and provides a useful context within which to conceptualize differences between species, populations, and individuals.
Alterations of
myc
,
myb
, and
ras
Ha
Proto-Oncogenes In Cancers Are Frequent and Show Clinical Correlation
Authors: Yokota Jun , Tsunetsugu-Yokota Yasuko , Battifora Hector , Le Fevre Carol , Cline Martin J.
Published: October 2006

Alterations of c-
myc
, c-
ras
Ha
, or c-
myb
oncogenes were found in more than one-third of human solid tumors. Amplification of c-
myc
occurred in advanced, widespread tumors or in aggressive primary tumors. Apparent allelic deletions of c-
ras
Ha
and c-
myb
can be correlated with progression and metastasis of carcinomas and sarcomas.
Theory and Modeling of Stereoselective Organic Reactions
Authors: Houk Kendall N. , Paddon-Row Michael N. , Rondan Nelson G. , Wu Yun-Dong , Brown Frank K. , Spellmeyer David C. , Metz James T. , Li Yi , Loncharich Richard J.
Published: October 2006

Theoretical investigations of the transition structures of additions and cycloadditions reveal details about the geometries of bond-forming processes that are not directly accessible by experiment. The conformational analysis of transition states has been developed from theoretical generalizations about the preferred angle of attack by reagents on multiple bonds and predictions of conformations with respect to partially formed bonds. Qualitative rules for the prediction of the stereochemistries of organic reactions have been devised, and semi-empirical computational models have also been developed to predict the stereoselectivities of reactions of large organic molecules, such as nucleophilic additions to carbonyls, electrophilic hydroborations and cycloadditions, and intramolecular radical additions and cycloadditions.
Flying Primates? Megabats Have the Advanced Pathway from Eye to Midbrain
Authors: Pettigrew John D.
Published: October 2006

The pattern of connections between the retina and midbrain has been determined with electrophysiological and neuroanatomical methods in bats representing the two major subdivisions of the
Chiroptera
. Megachiropteran fruit bats (megabats),
Pteropus
spp., were found to have an advanced retinotectal pathway with a vertical hemidecussation of the kind previously found only in primates. In contrast, the microchiropteran bat
Macroderma gigas
has the "ancestral" or symplesiomorphous pattern of retinotectal connections so far found in all vertebrates except primates. In addition to linking primates and megachiropteran bats, these findings suggest that flight may have evolved twice among the mammals.
Electrophoretic Separations of Large DNA Molecules by Periodic Inversion of the Electric Field
Authors: Carle Georges F. , Frank Mark , Olson Maynard V.
Published: October 2006

In gel electrophoresis, nucleic acids and protein-detergent complexes larger than a threshold size all migrate at the same rate. For DNA molecules, this effect can be overcome by the simple procedure of periodically inverting the electric field. Tuning the frequency of the field inversions from 10 to 0.01 hertz, makes it possible to resolve selectively DNA's in the size range 15 to >700 kilobase pairs.
Biochemical and Genetic Evidence for the Hepatitis B Virus Replication Strategy
Authors: Seeger Christoph , Ganem Don , Varmus Harold E.
Published: October 2006

Hepatitis B viruses synthesize their open circular DNA genomes by reverse transcription of an RNA intermediate. The details of this process have been examined with the use of mammalian hepatitis B viruses to map the sites for initiation and termination of DNA synthesis and to explore the consequences of mutations introduced at short, separated direct repeats (DR1 and DR2) implicated in the mechanisms of initiation. The first DNA strand to be synthesized is initiated within DR1, apparently by a protein primer, and the completed strand has a short terminal redundancy. In contrast, the second DNA strand begins with the sequence adjacent to DR2, but its 5′ end is joined to an oligoribonucleotide that contains DR1; thus the putative RNA primer has been transposed to the position of DR2. It is now possible to propose a detailed strategy for reverse transcription by hepatitis B viruses that can be instructively compared with that used by retroviruses.
Defective Sialic Acid Egress from Isolated Fibroblast Lysosomes of Patients with Salla Disease
Authors: Renlund Martin , Tietze Frank , Gahl William A.
Published: October 2006

Normal fibroblasts exposed to
N
-acetylmannosamine yielded lysosome-rich granular fractions loaded with free (unbound) sialic acid, whose velocity of egress increased with increasing initial loading. Fibroblast granular fractions of patients with Salla disease exhibited negligible egress of sialic acid, whether endogenous or derived from
N
-acetylmannosamine exposure. Salla disease represents the first disorder demonstrated to be caused by defective transport of a monosaccharide out of cellular lysosomes.
Peroxisomal Defects in Neonatal-Onset and X-Linked Adrenoleukodystrophies
Authors: Goldfischer Sidney , Collins Janna , Rapin Isabelle , Coltoff-Schiller Bernice , Chang Chung-Ho , Nigro Michael , Black Virginia H. , Javitt Norman B. , Moser Hugo W. , Lazarow Paul B.
Published: October 2006

Accumulation of very long chain fatty acids in X-linked and neonatal forms of adrenoleukodystrophy (ALD) appears to be a consequence of deficient oxidation of very long chain fatty acids, a function that has been attributed to peroxisomes. Peroxisomes were readily identified in liver biopsies taken from a patient having the X-linked disorder. However, in liver biopsies from a patient having neonatal-onset ALD, hepatocellular peroxisomes were greatly reduced in size and number, and sedimentable catalase was markedly diminished. The presence of increased concentrations of serum pipecolic acid and the bile acid intermediate, trihydroxycoprostanic acid, in the neonatal ALD patient are associated with a generalized diminution of peroxisomal activities that was not observed in the patient with X-linked ALD.
Transovarial Transmission of Murine Typhus Rickettsiae in
Xenopsylla cheopis
Fleas
Authors: Farhang-Azad A. , Traub R. , Baqar S.
Published: October 2006

It has been generally accepted that infected fleas do not pass on
Rickettsia mooseri
, or indeed any other known pathogen, to their progeny. It is reported here that such transovarial transmission does occur in laboratory-infected
Xenopsylla cheopis
fleas. By means of the direct fluorescent antibody test,
Rickettsia mooseri
was observed in cells of the hemolymph of infected fleas. As many as 11 percent of the adults and 2.9 percent of the larvae of the generation reared therefrom, had demonstrable rickettsiae. Moreover, batches of the F
1
fleas were capable of transmitting the infection to more than 18 percent of the rats they infested. The data support the contention that
Xenopsylla cheopis
fleas play an important role in the maintenance of murine typhus in rats in nature.
A Renal Countercurrent System in Marine Elasmobranch Fish: A Computer-Assisted Reconstruction
Authors: Lacy Eric R. , Reale Enrico , Schlusselberg Daniel S. , Smith Wade K. , Woodward Donald J.
Published: October 2006

Computer-aided techniques were used to reconstruct the complex renal tubular system in the dorsal kidney region of a marine elasmobranch fish, the little skate (
Raja erinacea
), from a series of light micrographs of serial sections. It was established that five individual segments of one nephron, consisting of two loops and a distal tubule, are arranged in parallel within an elongated closed tissue sac. Capillaries, which form a network around these nephron segments, enter and exit this sac at the same end. This anatomical arrangement suggests that a complex renal countercurrent multiplier system may be important in fluid regulation in these fish.
Synaptic Morphology and Differences in Sensitivity
Authors: Fields R. Douglas , Ellisman Mark H.
Published: October 2006

A relation between synaptic morphology and physiology was observed in an in vitro preparation of a sense organ (the ampulla of Lorenzini), in which activity was monitored from the primary afferent neurons before electron microscopic examination of the afferent synapses. The depth of the postsynaptic trough decreased as prefixation sensitivity of the sense organ decreased. This relation and other ultrastructural differences suggest that physiological properties of synapses are influenced by morphological features. Thus, synapses might be morphologically dynamic to modulate synaptic efficacy in relatively long-term phenomena.
Loss of M2 Muscarine Receptors in the Cerebral Cortex in Alzheimer's Disease and Experimental Cholinergic Denervation
Authors: Mash Deborah C. , Flynn Donna D. , Potter Lincoln T.
Published: October 2006

Cerebral cortex samples from patients with Alzheimer's disease and from rats after experimental cholinergic denervation of the cerebral cortex exhibited reductions in the presynaptic marker choline acetyltransferase activity and in the number of M2 muscarine receptors, with no change in the number of M1 receptors. These results are in keeping with evidence that M2 receptors function in cholinergic nerve terminals to regulate the release of acetylcholine, whereas M1 receptors are located on postsynaptic cells and facilitate cellular excitation. New M1-selective agonists and M2-selective antagonists directed at post- or presynaptic sites deserve consideration as potential agents for the treatment of the disease.
The Stability of DNA in Human Cerebellar Neurons
Authors: Slatkin D. N. , Friedman L. , Irsa A. P. , Micca P. L.
Published: October 2006

Human tissues have carbon-isotope ratios (13C/12C) that reflect dietary ratios. This observation has been used to determine the extent of metabolic turnover of DNA in cells of the adult human cerebellum (90 percent of which are neuronal). If adult human neuronal DNA were metabolically stable, its13C/12C would reflect that in the maternal diet during fetal development as nearly all neurons are formed during maturation of the fetal brain and do not undergo cell division thereafter. The13C/12C ratios in the food chains and body tissues of Europeans differ from corresponding American ratios by about 50 parts per million on the average. Therefore, turnover was studied by comparing13C/12C ratios in cerebellar DNA of American-born Americans, European-born Americans, and European-born Europeans. The13C/12C ratios in cerebellar DNA from European-born Americans were closer to13C/12C ratios in cerebellar DNA from European-born Europeans than from American-born Americans, indicating that there was little or no turnover of neuronal DNA.
The Mosaic Genome of Warm-Blooded Vertebrates
Authors: Bernardi Giorgio , Olofsson Birgitta , Filipski Jan , Zerial Marino , Salinas Julio , Cuny Gerard , Meunier-Rotival Michele , Rodier Francis
Published: October 2006

Most of the nuclear genome of warm-blooded vertebrates is a mosaic of very long (> > 200 kilobases) DNA segments, theisochores; these isochores are fairly homogeneous in base composition and belong to a small number of major classes distinguished by differences in guanine-cytosine (GC) content. The families of DNA molecules derived from such classes can be separated and used to study the genome distribution of any sequence which can be probed. This approach has revealed (i) that the distribution of genes, integrated viral sequences, and interspersed repeats is highly nonuniform in the genome, and (ii) that the base composition and ratio of CpG to GpC in both coding and noncoding sequences, as well as codon usage, mainly depend on the GC content of the isochores harboring the sequences. Thecompositional compartmentalizationof the genome of warm-blooded vertebrates is discussed with respect to its evolutionary origin, its causes, and its effects on chromosome structure and function.
Congenital Anomalies Induced in Hamster Embryos with Ribavirin
Authors: Kilham Lawrence , Ferm Virgil H.
Published: October 2006

Ribavirin, when given to pregnant hamsters in relatively small single doses, induces congenital anomalies of limbs, ribs, eyes, and central nervous system, as well as fetal deaths. On the basis of these findings, caution should be used in giving ribavirin to women of child-bearing age.
Sarcocystosis: A Clinical Outbreak in Dairy Calves
Authors: Frelier P. , Mayhew I. G. , Fayer R. , Lunde M. N..
Published: October 2006

Death and illness in a pen of eight yearling dairy heifers was caused by the protozoan parasite
Sarcocystis
. All animals had weight loss, weakness, marginal anemia, and elevated serum enzymes. Affected animals had high hemagglutinating antibody titers to
Sarcocystis
antigen. Affected tissues of the two animals that died demonstrated schizonts and young cysts during pathologic examination. The resident farm dog was shedding
Sarcocystis
sporocysts and was incriminated as the source of infection.
Z-DNA Forms Without an Alternating Purine-Pyrimidine Sequence in Solution
Authors: Feigon Juli , Wang Andrew H.-J. , van der Marel Gus A. , van Boom Jacques H. , Rich Alexander
Published: October 2006

Nuclear magnetic resonance spectra (proton and phosphorus-31) and ultraviolet absorption spectra of the DNA decamer d(br
5
CGbr
5
CGATbr
5
CGbr
5
CG), in which the central two adenine-thymine base pairs are out of order with the rest of the purine-pyrimidine alternation sequence, indicate that under appropriate solvent conditions (high salt and methanol) the molecule undergoes a structural transition from a right-handed B-DNA conformation to a left-handed Z-DNA conformation. Measurements of the two-dimensional nuclear Overhauser effect on the decamer indicate that all of the guanines as well as the two equivalent thymines adopt the syn conformation.
Chromatic Organization of Primate Cones
Authors: Marc Robert E. , Sperling Harry G.
Published: October 2006

The distributions of baboon retinal cones were mapped histochemically by light-stimulated reduction of nitroblue tetrazolium chloride. Blue cones were distributed regularly in the periphery; red and green cones were distributed randomly everywhere. The ordering of cone densities was green > red > blue.
Antileukemia Activity in the Oscillatoriaceae: Isolation of Debromoaplysiatoxin from
Lyngbya
Authors: Mynderse Jon S. , Moore Richard E. , Kashiwagi Midori , Norton Ted R.
Published: October 2006

Chloroform extracts of several seaweeds, of the family Oscillatoriaceae, from Enewetak Atoll, Marshall Islands, display activity against P-388 lymphocytic mouse leukemia. A P-388 active compound, debromoaplysiatoxin, has been isolated from
Lyngbya gracilis
and characterized. This compound also has dermonecrotic activity and may be the dermatitis-producing substance in
L. majuscula
, the causative agent of "swimmers' itch" outbreaks in Hawaiian waters.
Scotopic Vision Deficits in Young Monkeys Exposed to Lead
Authors: Bushnell Philip J. , Bowman Robert E. , Allen James R. , Marlar Rickey J.
Published: October 2006

Rhesus monkeys were reared on diets designed to produce blood lead concentrations of 14 (untreated), 55, or 85 micrograms per 100 milliliters for the first year of life. Eighteen months later, blood lead levels were normal in all animals. At this time, however, visual discrimination performance in the 85-microgram group was impaired under dim light relative both to their own performance under bright light and to the performance of the other groups under all light levels used. We interpret these results to reflect a deleterious, enduring impairment of scotopic visual function (night blindness) as a result of early lead intoxication.
X-Ray Structure of the Major Adduct of the Anticancer Drug Cisplatin with DNA:
cis
-[Pt(NH
3
)
2
{d(pGpG)}]
Authors: Sherman Suzanne E. , Gibson Dan , Wang Andrew H.-J. , Lippard Stephen J.
Published: October 2006

Crystals of the adduct of the anticancer drug
cis
-diamminedichloroplatinum(II),
cis
-DDP, with d(pGpG), its putative target on DNA in the cancer cell, have been obtained and used in an x-ray crystallographic study to elucidate the molecular structure to atomic resolution. Each of the four crystallographically independent
cis
-[Pt(NH
3
)
2
{d(pGpG)}] molecules is comprised of a square-planar platinum atom bonded to two ammonia ligands and two N(7) atoms of guanosine nucleosides from the same chain. Base stacking of the two adjacent guanine rings is completely disrupted by coordination to the
cis
-{Pt(NH
3
)
2
}
2+
unit. Comparison of the backbone and deoxyribose ring torsion angles with those found by previous (nuclear magnetic resonance spectroscopy) studies of this adduct in solution demonstrates that the solid state geometry is substantially the same as that in solution. The relevance of these results to the molecular mechanism of action of
cis
-DDP is discussed.
Evolution of Bunyaviruses by Genome Reassortment in Dually Infected Mosquitoes (
Aedes triseriatus
)
Authors: Beaty Barry J. , Sundin Daniel R. , Chandler Laura J. , Bishop David H. L.
Published: October 2006

Aedes triseriatus
mosquitoes became dually infected after ingesting two mutants of LaCrosse (LAC) virus simultaneously or after ingesting, by interrupted feeding, the two viruses sequentially within a 2-day period. After 2 weeks of incubation, approximately 25 percent of the vectors contained new virus genotypes as the result of RNA segment reassortment. New viruses were transmitted when the mosquitoes fed on mice. Viruses ingested more than 2 days after the initial infecting virus did not cause superinfection of the mosquito vectors.
Plasticity of Hippocampal Circuitry in Alzheimer's Disease
Authors: Geddes James W. , Monaghan Daniel T. , Cotman Carl W. , Lott Ira T. , Kim Ronald C. , Chui Helena Chang
Published: October 2006

Two markers of neuronal plasticity were used to compare the response of the human central nervous system to neuronal loss resulting from Alzheimer's disease with the response of rats to a similar neuronal loss induced by lesions. In rats that had received lesions of the entorhinal cortex, axon sprouting of commissural and associational fibers into the denervated molecular layer of the dentate gyrus was paralleled by a spread in the distribution of tritiated kainic acid-binding sites. A similar expansion of kainic acid receptor distribution was observed in hippocampal samples obtained postmortem from patients with Alzheimer's disease. An enhancement of acetylcholinesterase activity in the dentate gyrus molecular layer, indicative of septal afferent sprouting, was also observed in those patients with a minimal loss of cholinergic neurons. These results are evidence that the central nervous system is capable of a plastic response in Alzheimer's disease. Adaptive growth responses occur along with the degenerative events.
Detection of Single Base Substitutions by Ribonuclease Cleavage at Mismatches in RNA:DNA Duplexes
Authors: Myers Richard M. , Larin Zoia , Maniatis Tom
Published: October 2006

Single base substitutions can be detected and localized by a simple and rapid method that involves ribonuclease cleavage of single base mismatches in RNA:DNA heteroduplexes. A
32
P-labeled RNA probe complementary to wild-type DNA is synthesized in vitro and annealed to a test DNA containing a single base substitution. The resulting single base mismatch is cleaved by ribonuclease A, and the location of the mismatch is then determined by analyzing the sizes of the cleavage products by gel electrophoresis. Analysis of every type of mismatch in many different sequence contexts indicates that more than 50 percent of all single base substitutions can be detected. The feasibility of this method for localizing base substitutions directly in genomic DNA samples is demonstrated by the detection of single base mutations in DNA obtained from individuals with β-thalassemia, a genetic disorder in β-globin gene expression.