bluuebunny/crossref_metadata_2025 huggingface dataset:
The Molecular Control of Blood Cell Development
Authors: Sachs Leo
Published: October 2006

The establishment of a cell culture system for the clonal development of blood cells has made it possible to identify the proteins that regulate the growth and differentiation of different blood cell lineages and to discover the molecular basis of normal and abnormal cell development in blood forming tissues. A model system with myeloid blood cells has shown that (i) normal blood cells require different proteins to induce cell multiplication (growth inducers) and cell differentiation (differentiation inducers), (ii) there is a hierarchy of growth inducers as cells become more restricted in their developmental program, and (iii) a cascade of interactions between proteins determines the correct balance between immature and mature cells in normal blood cell development. Gene cloning has shown that there is a family of different genes for these proteins. Normal protein regulators of blood cell development can control the abnormal growth of certain types of leukemic cells and suppress malignancy by inducing differentiation to mature nondividing cells. Chromosome abnormalities that give rise to malignancy in these leukemic cells can be bypassed and their effects nullified by inducing differentiation, which stops cells from multiplying. These blood cell regulatory proteins are active in culture and in the body, and they can be used clinically to correct defects in blood cell development.
Bacteriophage M13 Procoat Protein Inserts Into the Plasma Membrane as a Loop Structure
Authors: Kuhn Andreas
Published: October 2006

The major coat protein of bacteriophage M13 is synthesized as a precursor, the procoat, with a typical leader (signal) sequence of 23 residues at its NH
2
-terminus. A fusion protein that contains the NH
2
-terminal 141 residues of cytoplasmic ribulokinase and all but the first ten residues of M13 procoat was made. The fusion protein inserts into the plasma membrane of
Escherichia coli
and is processed by leader peptidase to give rise to a leader peptide of 155 residues and the mature coat protein of 50 residues. The NH
2
-terminus of the leader peptide remains in the cytoplasm and is protected from protease added to the medium outside of the cell. This indicates that M13 procoat inserts into the membrane as a loop structure and that the NH
2
-terminus of a leader peptide remains within the cytoplasm during membrane insertion.
Neurometrics: Computer-Assisted Differential Diagnosis of Brain Dysfunctions
Authors: John E. R. , Prichep L. S. , Fridman J. , Easton P.
Published: October 2006

Normative developmental equations provide reliable descriptors of brain electrical activity in people 6 to 90 years old. Healthy persons display only chance deviations beyond predicted ranges. Patients with neurological impairment, subtle cognitive dysfunctions, or psychiatric disorders (including dementia and primary depression) show a high incidence of abnormal values. The magnitude of the deviations increases with clinical severity. Different disorders are characterized by distinctive profiles of abnormal values of brain electrical features. Computerized differential classification of some of these disorders can be achieved with high accuracy. Such classification, providing objective corroboration of brain dysfunctions, may be a useful adjunct to psychiatric diagnosis, which relies primarily on subjective clinical impressions. These methods may provide independent criteria for diagnostic validity, evaluations of treatment efficacy, and more individualized therapy.
Legal Rights and Duties in the AIDS Epidemic
Authors: Dickens Bernard M.
Published: October 2006

This article provides an overview of some major areas of legal concern in which the AIDS epidemic is having an impact. The rights of infected individuals to testing, treatment, and confidentiality are reviewed, and emphasis is given to their claims to nondiscrimination regarding access to health care, employment, housing, education, insurance, and related interests. Infected persons' duties to contain transmission of AIDS are outlined under principles of criminal and civil law, including liability for provision of contaminated blood products. Uninfected people's general rights to protection are considered, and health professionals' and authorities' rights and duties are given more detailed attention. In conclusion, some legal developments outside the United States are reviewed.
Glycosyl-Phosphatidylinositol Moiety That Anchors
Trypanosoma brucei
Variant Surface Glycoprotein to the Membrane
Authors: Ferguson Michael A. J. , Homans Steve W. , Dwek Raymond A. , Rademacher Thomas W.
Published: October 2006

Two forms of protein-membrane anchor have been described for the externally disposed glycoproteins of eukaryotic plasma membranes; namely, the hydrophobic transmembrane polypeptide and the complex glycosylphosphatidylinositol (G-PI) moiety. The chemical structures of the major species of G-PI anchors found on a single variant surface glycoprotein (VSG) of the parasitic protozoan
Trypanosoma brucei
were determined by a combination of nuclear magnetic resonance spectroscopy, mass spectrometry, chemical modification, and exoglycosidase digestions. The G-PI anchor was found to be heterogeneous with respect to monosaccharide sequence, and several novel glycosidic linkages were present. The results are pertinent to the mechanism of the biosynthesis of G-PI anchors.
Electric Field X-ray Scattering Measurements on Tobacco Mosaic Virus
Authors: Koch M. H. J. , Dorrington E. , Kläring R. , Michon A. M. , Sayers Z. , Marquet R. , Houssier C.
Published: October 2006

The feasibility of electric field x-ray solution scattering with biological macromolecules was investigated. Electric field pulses (1.25 to 5.5 kilovolts per centimeter) were used to orient tobacco mosaic virus in solution (4.5 milligrams per milliliter). The x-ray scattering is characteristic of isolated oriented particles. The molecular orientation and its field-free decay were monitored with a time resolution of 2 milliseconds by means of synchrotron radiation and a multiwire proportional area detector. The method should also be applicable to synthetic polymers and inorganic colloids.
Fifty Centuries of Right-Handedness: The Historical Record
Authors: Coren Stanley , Porac Clare
Published: October 2006

A survey of more than 5000 years of art works, encompassing 1180 scorable instances of unimanual tool or weapon usage, revealed no systematic trends in hand usage. The right hand was used in an average of 93 percent of the cases, regardless of which historical era or geographic region was assessed.
Somatostatin: Widespread Abnormality in Tissues of Spontaneously Diabetic Mice
Authors: Patel Y. C. , Cameron D. P. , Stefan Y. , Malaisse-Lagae F. , Orci L.
Published: October 2006

Diabetic mice of the C57BL/6J obob and C57BL/Ks dbdb strains show a reduction in pancreatic somatostatin concentration accompanied in the obob strain by a striking decrease in the number of somatostatin-containing cells in the islets. Somatostatin concentration is also decreased in the stomach but increased in the hypothalamus. These findings suggest different control mechanisms for somatostatin in the hypothalamus compared to the gut and pancreas and exclude a primary genetic abnormality of somatostatin cells in the mutants.
Lactate-Supported Synaptic Function in the Rat Hippocampal Slice Preparation
Authors: Schurr Avital , West Catherine A. , Rigor Benjamin M.
Published: October 2006

The present study was undertaken to examine the possibility that cerebral energy metabolism can be fueled by lactate. As a sole energy substrate, lactate supported normal synaptic function in rat hippocampal slices for hours without any sign of deterioration. Slices that were synaptically silent as a result of glucose depletion could be reactivated with lactate to show normal synaptic function. When slices were exposed to the glycolytic inhibitor iodoacetic acid, lactate-supported synaptic function was unaffected, whereas that supported by glucose was completely abolished. This indicated that lactate was metabolized directly via pyruvate to enter the tricarboxylic acid cycle. Thus, under conditions that lead to lactate accumulation (cerebral ischemia) this "end product" may be a useful alternative as a substrate for energy metabolism.
Induction of Gene Amplification by Arsenic
Authors: Lee Te-Chang , Tanaka Noriho , Lamb Patricia W. , Gilmer Tona M. , Barrett J. Carl
Published: October 2006

Arsenic is a well-established carcinogen in humans, but there is little evidence for its carcinogenicity in animals and it is inactive as an initiator or tumor promoter in two-stage models of carcinogenicity in mice. Two arsenic salts (sodium arsenite and sodium arsenate) induced a high frequency of methotrexate-resistant 3T6 cells, which were shown to have amplified copies of the dihydrofolate reductase gene. The ability of arsenic to induce gene amplification may relate to its carcinogenic effects in humans since amplification of oncogenes is observed in many human tumors. The inability of arsenic to induce gene mutations may relate to the negative results of arsenic in long-term animal studies and suggests that these experiments may not detect some environmental agents that act late in the carcinogenic process in humans.
Mediatory Role of Calcium and Guanosine 3′,5′-Monophosphate in Adrenocorticotropin-Induced Steroidogenesis by Adrenal Cells
Authors: Perchellet Jean-Pierre , Sharma Rameshwar K.
Published: October 2006

When incubated in a calcium-free medium, isolated rat fasciculata cells showed neither an increase in the concentration of guanocine 3′,5′-monophosphate (cyclic GMP) nor an increase in corticosterone production in response to adrenocorticotropic hormone (ACTH). In response to submaximum and maximum steroidogenic concentrations of ACTH, corticosterone formation was directly proportional to increases in calcium concentration ranging from 0 to 2.5 m
M
. Higher concentrations of calcium, however, inhibited maximal ACTH-induced steroidogenesis. In the absence of ACTH, calcium did not stimulate cyclic GMP accumulation and corticosterone formation. ACTH-induced corticosterone synthesis, preceded by an increase in cyclic GMP, was restored when ACTH and calcium were both present in the medium. Cyclic GMP or dibutryl cyclic GMP-induced steroidogenesis was substantially reduced in the absence of calcium, but in contrast to the ACTH effect a significant amount of corticosterone formation occurred without calcium. It is proposed that at the physiological concentrations of the hormone, calcium regulates the transduction of information between hormone receptors and guanylate cyclase.
Endorphins: Naloxone Fails to Alter Experimental Pain or Mood in Humans
Authors: Grevert Priscilla , Goldstein Avram
Published: October 2006

In 30 human subjects, experimental pain was produced by either ischemia or cold-water immersion. In a double-blind procedure, intravenous doses of up to 10 milligrams of naloxone hydrochloride in saline were indistinguishable from similarly administered saline alone. There were no effects on subjective pain ratings, finger plethysmograph recordings, or responses to mood-state questionnaires. These laboratory procedures do not activate any functionally significant pain-attenuating or mood-altering effect of endorphins.
Production of Immunoglobulin Isotypes by Ly-1
+
B Cells in Viable Motheaten and Normal Mice
Authors: Sidman Charles L. , Shultz Leonard D. , Hardy Richard R. , Hayakawa Kyoko , Herzenberg Lee A.
Published: October 2006

Almost all B cells in autoimmune mice with the viable motheaten (
me
v
) mutation express the Ly-1 cell surface antigen, which marks a minor population of B cells constituting a separate lineage in normal mice. Immunoglobulins primarily of the M and G3 classes, which in both normal and
me
v
mice contain high levels of lambda light chain, are produced in excess in
me
v
mice. These and other observations suggest that the development of B cells that express Ly-1 is regulated independently from the development of B cells that do not express Ly-1. B cells bearing the Ly-1 surface antigen may play specialized roles in the normal immune system and in autoimmunity by regulating other B cells via lymphokines, by producing antibodies to self and certain foreign antigens, and by preferentially secreting immunoglobulin M and immunoglobulin G3.
Blockade of Visual Excitation and Adaptation in
Limulus
Photoreceptor by GDP-β-S
Authors: Fein Alan
Published: October 2006

Light causes both depolarization and adaptation to light in
Limulus
ventral photoreceptors. Both visual excitation and adaptation were blocked by guanosine 5′-
O
-(2-thiodiphosphate) (GDP-β-S), a metabolically stable analog of guanosine 5′-diphosphate (GDP). However, GDP-β-S did not block the excitation caused by injection of inositol 1,4,5-trisphosphate into the cell. These results suggest a molecular cascade of visual excitation and adaptation: Light isomerizes the visual pigment rhodopsin, which in turn activates a guanyl nucleotide-binding protein. The binding protein then stimulates production of inositol 1,4,5-trisphosphate, which causes release of calcium from the endoplasmic reticulum.
Mummy of the "Elder Lady" in the Tomb of Amenhotep II: Egyptian Museum Catalog Number 61070
Authors: Harris James E. , Wente Edward F. , Cox Charles F. , El Nawaway Ibrahim , Kowalski Charles J. , Storey Arthur T. , Russell William R. , Ponitz Paul V. , Walker Geoffrey F.
Published: October 2006

An unidentified female mummy found in a cache of great kings and queens in 1898 in the Valley of the Kings was examined from the viewpoint of Egyptology, x-ray cephalometry, biostatistics, and biochemistry. The result was the identification of Queen Tiye, of the Eighteenth Dynasty, wife of Amenhotep III and mother of Akhenaton.
Human Serial Learning: Enhancement with Arecholine and Choline Impairment with Scopolamine
Authors: Sitaram N. , Weingartner Herbert , Gillin J. Christian
Published: October 2006

Arecholine (4 milligrams), a cholinergic agonist, and choline (10 grams), a precursor of acetylcholine, significantly enhanced serial learning in normal human subjects. The subjects received methscopolamine prior to both arecholine and placebo injections. Conversely, scopolamine (0.5 milligram), a cholinergic antagonist, impaired learning and this impairment was reversed by a subsequent injection of arecholine. The degree of enhancement produced by arecholine and choline and the impairment after scopolamine were inversely proportional to the subject's performance on placebo; that is, "poor" performers were more vulnerable to both the enhancing effect of cholinergic agonist and precursor and the impairment after cholinergic antagonist than "good" performers.
A Yeast Gene That Is Essential for Release from Glucose Repression Encodes a Protein Kinase
Authors: Celenza John L. , Carlson Marian
Published: October 2006

The
SNF1
gene plays a central role in carbon catabolite repression in the yeast
Saccharomyces cerevisiae
, namely that
SNF1
function is required for expression of glucose-repressible genes. The nucleotide sequence of the cloned
SNF1
gene was determined, and the predicted amino acid sequence shows that
SNF1
encodes a 72,040-dalton polypeptide that has significant homology to the conserved catalytic domain of mammalian protein kinases. Specific antisera were prepared and used to identify the
SNF1
protein. The protein was shown to transfer phosphate from adenosine triphosphate to serine and threonine residues in an in vitro autophosphorylation reaction. These findings indicate that
SNF1
encodes a protein kinase and suggest that protein phosphorylation plays a critical role in regulation by carbon catabolite repression in eukaryotic cells.
Genetic Selection of a
Plasmodium
-Refractory Strain of the Malaria Vector
Anopheles gambiae
Authors: Collins Frank H. , Sakai Richard K. , Vernick Kenneth D. , Paskewitz Susan , Seeley Douglas C. , Miller Louis H. , Collins William E. , Campbell Carlos C. , Gwadz Robert W.
Published: October 2006

The anopheline mosquito is the target in most malaria control programs, primarily through the use of residual insecticides. A mosquito was studied that is refractory to most species of malaria through a genetically controlled mechanism. A strain of
Anopheles gambiae
, which was selected for complete refractoriness to the simian malaria parasite
Plasmodium cynomolgi
, also has varying degrees of refractoriness to most other malaria species examined, including the human parasites
P. falciparum
,
P. ovale
, and
P. vivax
for which this mosquito is the principal African vector. Furthermore, the refractoriness extends to other subhuman primate malarias, to rodent malaria, and to avian malaria. Refractoriness is manifested by encapsulation of the malaria ookinete after it completes its passage through the mosquito midgut, approximately 16 to 24 hours after ingestion of an infective blood meal. Fully encapsulated ookinetes show no abnormalities in parasite organelles, suggesting that refractoriness is due to an enhanced ability of the host to recognize the living parasite rather than to a passive encapsulation of a dead or dying parasite. Production of fully refractory and fully susceptible mosquito strains was achieved through a short series of selective breeding steps. This result indicates a relatively simple genetic basis for refractoriness. In addition to the value these strains may serve in general studies of insect immune mechanisms, this finding encourages consideration of genetic manipulation of natural vector populations as a malaria control strategy.
Separation of Large DNA Molecules by Contour-Clamped Homogeneous Electric Fields
Authors: Chu Gilbert , Vollrath Douglas , Davis Ronald W.
Published: October 2006

Electric fields can be manipulated by a method in which multiple electrodes are arranged along a closed contour and clamped to predetermined electric potentials. This method may be applied to a broad range of problems in the separation of macromolecules by gel electrophoresis. DNA molecules as large as 2 megabases can be well separated with a contour-clamped homogeneous electric field alternating between two orientations 120° apart. The pattern of separation is independent of position in the gel, which is an advantage over previous methods. DNA less than 50 kilobases can be separated without distortion even at high voltage with a nonalternating contour-clamped homogeneous field. Decreased band broadening in DNA less than 200 bases can be achieved with a contour-clamped inhomogeneous field.
The Molecular Genetics of Cancer
Authors: Bishop J. Michael
Published: October 2006

The search for genetic damage in neoplastic cells now occupies a central place in cancer research. Diverse examples of such damage are in hand, and they in turn hint at biochemical explanations for neoplastic growth. The way may be open to solve the riddles of how normal cells govern their replication and why cancer cells do not.
Modulation of Memory Processing by Cholecystokinin: Dependence on the Vagus Nerve
Authors: Flood James F. , Smith Gary E. , Morley John E.
Published: October 2006

Allowing mice access to food immediately after an aversive training session enhances memory retention. Cholecystokinin-octapeptide (CCK-8), which is a gastrointestinal hormone released during feeding, also enhances memory retention when administered intraperitoneally. This memory-enhancing effect of CCK-8 is blocked when the vagus nerve is cut, indicating that CCK-8 may produce its effect on memory retention by activating ascending fibers in the vagus nerve. Thus, CCK-8, a peripherally acting peptide, may mediate the memory-enhancing effects of feeding.
Sequence-Specific Packaging of DNA in Human Sperm Chromatin
Authors: Gatewood J. M. , Cook G. R. , Balhorn R. , Bradbury E. M. , Schmid C. W.
Published: October 2006

The DNA in human sperm chromatin is packaged into nucleoprotamine (∼85%) and nucleohistone (∼15%). Whether these two chromatin fractions are sequence-specific subsets of the spermatozoon genome is the question addressed in this report. Sequence-specific packaging would suggest distinct structural and functional roles for the nucleohistone and nucleoprotamine in late spermatogenesis or early development or both. After removal of histones with 0.65
M
NaCl, exposed DNA was cleaved with Bam HI restriction endonuclease and separated by centrifugation from insoluble nucleoprotamine. The DNA sequence distribution of nucleohistone DNA in the supernatant and nucleoprotamine DNA in the pellet was compared by cloning size-selected single-copy sequences and by using the derived clones as probes of nucleohistone DNA and nucleoprotamine DNA. Two clones derived from nucleohistone DNA preferentially hybridized to nucleohistone DNA, and two clones derived from nucleoprotamine DNA preferentially hybridized to nucleoprotamine DNA, which demonstrated the existence of sequence-specific nucleohistone and nucleoprotamine components within the human spermatozoon.
Antisense RNA Inactivation of Myosin Heavy Chain Gene Expression in
Dictyostelium discoideum
Authors: Knecht David A. , Loomis William F.
Published: October 2006

The role of myosin in the contraction of striated muscle cells is well known, but its importance in nonmuscle cells is not yet clear. The function of myosin in
Dictyostelium discoideum
has been investigated by isolating cells which specifically lack myosin heavy chain (MHC A) protein. Cells were transformed with a vector encoding RNA complementary to
mhcA
messenger RNA (antisense RNA). Stable transformants have a dramatic reduction in the amount of MHC A protein, grow slowly, and generate giant multinucleated progeny, indicating an impairment in cytokinesis. Surprisingly, the cells adhere to surfaces, extend pseudopods and are capable of ameboid locomotion. The developmental sequence that is initiated by starving cells is severely impaired by the lack of myosin. The cells are unable to form multicellular aggregates normally and do not undergo subsequent morphogenesis. By changing the food source from liquid medium to bacteria, expression of the endogenous
mhcA
messenger RNA can be increased relative to expression of antisense RNA. When grown in this way, the transformed cells accumulate MHC A protein, remain mononucleate, and proceed through development normally.
Molecular Analysis of a Constitutional X-Autosome Translocation in a Female with Muscular Dystrophy
Authors: Bodrug S. E. , Ray P. N. , Gonzalez I. L. , Schmickel R. D. , Sylvester J. E. , Worton R. G.
Published: October 2006

The gene responsible for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) maps to the X chromosome short arm, band Xp21. In a few females with DMD or BMD, the Xp21 region is disrupted by an X-autosome translocation. Accumulating evidence suggests that the exchange has physically disrupted the DMD/BMD locus to cause the disease. One affected female with a t(X;21)(p21;p12) translocation was studied in detail. The exchange points from both translocation chromosomes were cloned, restriction-mapped, and sequenced. The translocation is reciprocal, but not conservative. A small amount of DNA is missing from the translocated chromosomes; 71 to 72 base pairs from the X chromosome and 16 to 23 base pairs from the 28
S
ribosomal gene on chromosome 21.
Linkage of Functional and Structural Heterogeneity in Proteins: Dynamic Hole Burning in Carboxymyoglobin
Authors: Campbell Blair F. , Chance Mark R. , Friedman Joel M.
Published: October 2006

Inhomogeneous broadening of the 760-nanometer photoproduct band of carboxymyoglobin at cryogenic temperatures has been demonstrated with a dynamic hole burning technique. Line-shape changes and frequency shifts in this spectral band are generated by ligand recombination and are shown not to be the result of structural relaxation below 60 K. The observation of dynamic hole burning exposes the relation between the structural disorder responsible for the inhomogeneous broadening and the well-known distributed ligand rebinding kinetics. The findings provide direct evidence for the functional relevance of conformational substates in myoglobin rebinding. In addition, a general protocol for evaluating the relative contributions of structural relaxation and hole burning to the spectral changes accompanying ligand rebinding in hemeproteins is presented.
Transmission of a Female Sex Pheromone Thwarted by Males in the Spider
Linyphia litigiosa
(Linyphiidae)
Authors: Watson Paul J.
Published: October 2006

When a male Sierra dome spider (
Linyphia litigiosa
) encounters a virgin female that has been sexually mature for 7 to 10 days, he rapidly packs the silk of her web into a tight mass. This behavior hinders evaporation of a male-attractant chemical that such highly receptive females apply to their webs. The male thereby reduces the likelihood that his mating partner will attract rival males.
Static and Initiator Protein-Enhanced Bending of DNA at a Replication Origin
Authors: Koepsel Richard R. , Khan Saleem A.
Published: October 2006

DNA bending has been suggested to play a role in the regulation of gene expression, initiation of DNA replication, DNA packaging, and the recognition of specific DNA sequences by proteins. It has recently been demonstrated that DNA bending can be sequence-directed. Bent DNA has also been observed as a consequence of sequence-specific binding of proteins to DNA. In this report DNA of plasmid pT181 is shown to contain a bend at the replication origin. Furthermore, this bend is enhanced by the binding of the pT181 replication initiator protein, RepC, to the origin.
Structure and Diversity of the Human T-Cell Receptor β-Chain Variable Region Genes
Authors: Tillinghast Jeffrey P. , Behlke Mark A. , Loh Dennis Y.
Published: October 2006

In order to characterize the variability of the expressed human T-cell receptor (TCR) β-chain repertoire and contrast this variability to the known murine β-chain repertoire, 15 independent complementary DNA (cDNA) clones containing TCR β-chain variable region (V
β
) genes were isolated from a human tonsil cDNA library. The nucleotide and derived amino acid sequences of these 15 V
β
genes were analyzed together with 7 previously defined sequences. Fifteen different human V
β
genes could be identified from 22 independent sequences. By means of DNA hybridization and sequence homology comparisons, it was possible to group these 15 genes into ten distinct V
β
subfamilies, each containing from one to seven members. Minimal polymorphism was noted between individuals, except in multimember subfamilies. The amino acid sequences of these genes contain conserved amino acids that are also shared by murine TCR V
β
genes and immunoglobulins; no features were found that distinguish human V
β
genes from their murine counterparts. Evaluation of secondary structure showed that maximum variability coincides with generally hydrophilic portions of the amino acid sequence, while specific hydrophobic regions were conserved in all V
β
genes examined.
Ultraviolet Irradiation Transforms C3H10T1/2 Cells to a Unique, Suppressible Phenotype
Authors: Herschman Harvey R. , Brankow David W.
Published: October 2006

Transformation of C3H10T1/2 cells by exposure to ultraviolet (UV) irradiation followed by tetradecanoyl phorbol acetate (TPA) has been used as a model of two-stage carcinogenesis. However, cells cloned from UV-TPA-induced foci (UV-TDTx cells) had a unique phenotype. Cloned UV-TDTx cells appeared transformed in pure culture but were unable to form foci when cocultured with C3H10T1/2 cells. However, in the presence of TPA, UV-TDTx cells form foci in mixed culture with C3H10T1/2 cells. This phenotype was the only one observed for UV-TPA transformants. These data suggest that (i) communal suppression of cell division is a discrete phenomenon that must be overcome as one step in the multistage process of transformation, and (ii) this protocol permits the routine isolation of transformed cells responsive to density-dependent growth suppression.
Characterization and Chromosomal Localization of a cDNA Encoding Brain Amyloid of Alzheimer's Disease
Authors: Goldgaber Dmitry , Lerman Michael I. , McBride O. Wesley , Saffiotti Umberto , Gajdusek D. Carleton
Published: October 2006

Four clones were isolated from an adult human brain complementary DNA library with an oligonucleotide probe corresponding to the first 20 amino acids of the β peptide of brain amyloid from Alzheimer's disease. The open reading frame of the sequenced clone coded for 97 amino acids, including the known amino acid sequence of this polypeptide. The 3.5-kilobase messenger RNA was detected in mammalian brains and human thymus. The gene is highly conserved in evolution and has been mapped to human chromosome 21.
Model Studies in Molecular Recognition
Authors: Rebek Julius
Published: October 2006

Recognition at the molecular level is a fundamental characteristic of biochemical systems. Recent models developed in bioorganic chemistry have revealed the importance of complementarity in size, shape, and functional groups in molecular recognition. Structures that feature a cleft are particularly effective in regard to complementarity since functional groups attached to the interior of the cleft converge on substrates held inside. The molecular clefts offer the advantage of efficient construction; their surfaces can be tailored for specific applications. This article describes their use for recognition of acids, bases, amino acids, metal ions, and neutral substrates. Their ability to provide microenvironments complementary to asymmetric molecules and their future promise are discussed.
Retroviral Vector-Mediated Gene Transfer into Human Hematopoietic Progenitor Cells
Authors: Gruber Harry E. , Finley Kim D. , Hershberg Robert M. , Katzman Scott S. , Laikind Paul K. , Seegmiller J. Edwin , Friedmann Theodore , Yee Jing-Kuan , Jolly Douglas J.
Published: October 2006

The transfer of the human gene for hypoxanthine phosphoribosyltransferase (HPRT) into human bone marrow cells was accomplished by use of a retroviral vector. The cells were infected in vitro with a replication-incompetent murine retroviral vector that carried and expressed a mutant HPRT complementary DNA. The infected cells were superinfected with a helper virus and maintained in long-term culture. The production of progeny HPRT virus by the bone marrow cells was demonstrated with a colony formation assay on cultured HPRT-deficient, ouabain-resistant murine fibroblasts. Hematopoietic progenitor cells able to form colonies of granulocytes or macrophages (or both) in semisolid medium in the presence of colony stimulating factor were present in the nonadherent cell population. Colony forming units cloned in agar and subsequently cultured in liquid medium produced progeny HPRT virus, indicating infection of this class of hematopoietic progenitor cell.
Molecular Defects in a Human Immunoglobulin κ Chain Deficiency
Authors: Stavnezer-Nordgren Janet , Kekish Olga , Zegers Ben J. M.
Published: October 2006

The molecular basis of a human immunoglobulin deficiency characterized by the complete absence of κ chains has been investigated by nucleotide sequence analyses of a patient's κ constant region (C
κ
) genes. Both of his C
κ
genes had a single point mutation, resulting in the loss of the invariant tryptophan from one allele and of an invariant cysteine from the other allele. These results indicate that neither of the patient's C
κ
alleles encoded a κ chain that could form a stable intradomain disulfide bond, although peculiarities in the expression of κ chains in the patient's family suggest that other factors may be involved.
A Common Origin pf Rickettsiae and Certain Plant Pathogens
Authors: Weisburg William G. , Woese Carl R. , Dobson Michael E. , Weiss Emilio
Published: October 2006

On the basis of ribosomal RNA sequence comparisons, the rickettsia
Rochalimaea quintana
has been found to be a member of subgroup 2 of the α subdivision of the so-called purple bacteria, which is one of about ten major eubacterial divisions. Within subgroup α-2,
R. quintana
is specifically related to the agrobacteria and rhizobacteria, organisms that also have close associations with eukaryotic cells. This genealogical grouping of the rickettsiae with certain plant pathogens and intracellular symbionts suggests a possible evolution of the rickettsiae from plant-associated bacteria.
Recombinant Human Tumor Necrosis Factor-α: Effects on Proliferation of Normal and Transformed Cells in Vitro
Authors: Sugarman Barry J. , Aggarwal Bharat B. , Hass Philip E. , Figari Irene S. , Palladino Michael A. , Shepard H. Michael
Published: October 2006

Modulation of the growth of human and murine cell lines in vitro by recombinant human tumor necrosis factor-α (rTNF-α) and recombinant human interferon-γ (rIFN-γ) was investigated. rTNF-α had cytostatic or cytolytic effects on only some tumor cell lines. When administered together with rIFN-γ, rTNF-α showed enhanced antiproliferative effects on a subset of the cell lines tested. In contrast to its effects on sensitive tumor cells, rTNF-α augmented the growth of normal diploid fibroblasts. Variations in the proliferative response induced by rTNF-α were apparently not due to differences in either the number of binding sites per cell or their affinity for rTNF-α. These observations indicate that the effects of rTNF-α on cell growth are not limited to tumor cells, but rather that this protein may have a broad spectrum of activities in vivo.
Adrenal-Mediated Endogenous Metabolites Inhibit Puberty in Female Mice
Authors: Novotny Milos , Jemiolo Bozena , Harvey Scott , Wiesler Donald , Marchlewska-Koj Anna
Published: October 2006

While assessing a potential role of adrenal glands in the production of the hitherto unidentified puberty-delaying pheromone of female mice, the urinary volatile profiles of normal and adrenalectomized animals were quantitatively compared. Six components, whose concentrations were depressed after adrenalectomy, were identified: 2-heptanone,
trans
-5-hepten-2-one,
trans
-4-hepten-2-one,
n
-pentyl acetate,
cis
-2-penten-1-yl acetate, and 2,5-dimethylpyrazine. When these laboratory-synthesized chemicals were added (in their natural concentrations) to either previously inactive urine from adrenalectomized females or plain water, the biological activity was fully restored.
Coupling of Action Potential Activity Between Unmyelinated Fibers in the Peripheral Nerve of Monkey
Authors: Meyer Richard A. , Raja Srinivasa N. , Campbell James N.
Published: October 2006

Bidirectional coupling of action potential activity occurs between unmyelinated fibers in the normal peripheral nerve of monkey. The site of coupling is near the cutaneous nociceptive receptor associated with one of the fibers. This coupling could be due to an electrical synapse and could provide the basis for the flare associated with the axon reflex.
Histological Demonstration of Mosaicism in a Series of Chimeric Rats Produced Between Congenic Strains
Authors: Weinberg W. C. , Howard J. C. , Iannaccone P. M.
Published: October 2006

Experimental chimeras were produced by aggregating morulae from congenic strains of PVG rats differing in the major histocompatibility complex (RT1). Monoclonal antibodies against variant class I antigens of the two strains were directly conjugated to iodine-125 and applied to tissue sections. Autoradiograms allowed examination of most internal tissues. The proportion of PVG-RT1
a
cells in the erythrocyte populations of the chimeras varied from 8 to 70 percent, as determined with fluorescence-activated flow cytometry. Digital analysis of autoradiograms demonstrated that the contribution of PVG-RT1
a
cells to the livers of the chimeras ranged from 34 to 86 percent. Patches of cells of each genotype in the liver were geometrically complex, with large variations in size. The thymus, but not the spleen, showed evidence of oligoclonal development. The adrenal cortex revealed a radially striped pattern, suggestive of clonal expansion of stem cells. With this approach it is possible to measure cell distribution in chimeras through direct histological visualization, which may prove useful in the study of rat organogenesis.
Phagocytes as Carcinogens: Malignant Transformation Produced by Human Neutrophils
Authors: Weitzman Sigmund A. , Weitberg Alan B. , Clark Edward P. , Stossel Thomas P.
Published: October 2006

In a study of the relation between chronic inflammation and carcinogenesis, C3H mouse fibroblasts of the 10T 1/2 clone 8 line (10T 1/2 cells) were exposed to human neutrophils stimulated to synthesize reactive oxygen intermediates or to a cell-free enzymatic system generating superoxide (xanthine oxidase plus hypoxanthine). After exposure, the 10T 1/2 cells were either placed in tissue culture or immediately injected into athymic nude mice. Both malignant and benign tumors developed in the mice injected with treated cells, but not in those injected with control cells; in one instance cells grown from one of the benign tumors subsequently developed a malignant phenotype. Malignant transformation was also observed in treated cells in the experiments in vitro.
Auditory Midbrain Responses Parallel Spectral Integration Phenomena
Authors: Ehret Günter , Merzenich Michael M.
Published: October 2006

Resolving the frequency components of complex sound spectra including speech is an inherent, important accomplishment of the auditory nervous systems of vertebrates. The critical perceptual unit in the frequency domain, the critical bandwidth, has a simple functional equivalent within the principal midbrain auditory nucleus—the central nucleus of the inferior colliculus.
Response to Ethanol Reduced by Past Thiamine Deficiency
Authors: Martin Peter R. , Majchrowicz Edward , Tamborska Ewa , Marietta Cheryl , Mukherjee Anil B. , Eckardt Michael J.
Published: October 2006

Ethanol-induced intoxication and hypothermia were studied in rats approximately 7 months after severe thiamine deficiency, when treated rats appeared to have recovered their physical health. Previously induced thiamine deficiency without prior ethanol exposure significantly decreased the area under the curve plotted for the concentration of ethanol in blood and also decreased behavioral impairment and hypothermia due to ethanol exposure. Pathophysiologic changes resulting from thiamine deficiency may contribute to both the pharmacodynamic and pharmacokinetic tolerance to ethanol in chronic alcoholics.
Hippocampal Efferents Reach Widespread Areas of Cerebral Cortex and Amygdala in the Rhesus Monkey
Authors: Rosene Douglas L. , Van Hoesen Gary W.
Published: October 2006

The subiculum of the primate hippocampal formation stands at the end of a polarized sequence of intrinsic hippocampal efferents and is the source of efferents to the medial frontal cortex, the caudal cingulate gyrus, and the parahippocampal area and amygdala in the temporal lobe. In addition, the subiculum sends subcortical efferents to the septum and diencephalon.
Thermoregulation Is Impaired in an Environment Without Circadian Time Cues
Authors: Fuller Charles A. , Sulzman Frank M. , Moore-Ede Martin C.
Published: October 2006

Squirrel monkeys synchronized to a 24-hour light-dark cycle show a prominent circadian rhythm in body temperature which is regulated against mild environmental cold exposures throughout the 24-hour day. However, cold exposures produce significant decreases in core body temperature when the circadian rhythms of the animal are free-running in the absence of environmental time cues. Effective thermoregulation appears to require the precise internal synchronization of the circadian timekeeping system.
Anosmia in Male Rhesus Monkeys Does Not Alter Copulatory Activity with Cycling Females
Authors: Goldfoot David A. , Essock-Vitale Susan M. , Asa Cheryl S. , Thornton Janice E. , Leshner Alan I.
Published: October 2006

Three adult male rhesus monkeys were tested daily with intact adult female partners over the course of four or five menstrual cycles. The males were made permanently anosmic by chemical ablation of the olfactory epithelium after the second or fourth cycle was completed. All males continued to display typical cycles of copulation with their partners after the anosmia procedures, with the shortest latencies to ejaculation occurring during the periovulatory phase of the partner's ovulatory cycle. Hence, female attractivity and cyclic copulatory performance of rhesus monkeys are not dependent upon olfactory signals.
Radiation from Tritiated Thymidine Perturbs the Cell Cycle Progression of Stimulated Lymphocytes
Authors: Pollack Alan , Bagwell C. Bruce , Irvin George L.
Published: October 2006

Tritiated thymidine was found to affect the cell cycle progression of phytohemagglutinin-stimulated human lymphocytes. By means of flow cytometry a statistically significant increase in the G
2
and M phases of the cell cycle was observed in cultures with low concentrations of tritiated thymidine added 18 hours before the cultures were harvested.
Mitochondrial DNA Analyses and the Origin and Relative Age of Parthenogenetic Lizards (Genus
Cnemidophorus
)
Authors: Brown Wesley M. , Wright John W.
Published: October 2006

Morphological, karyological, and allozyme analyses indicate that the parthenogenetic lizards
Cnemidophorus neomexicanus
and diploid
C. tesselatus
are hybrids formed, respectively, by crosses involving the bisexual species
C. tigris
and
C. inornatus
, and
C. tigris
and
C. septemvittatus
. Mitochondrial DNA, which is inherited maternally, was obtained from each of these species. Analyses of the mitochondrial DNA's and their restriction endonuclease digestion products by electron microscopy and agarose gel electrophoresis support the hybridization hypothesis by indicating that
C. tigris
(specifically the subspecies marmoratus) was the maternal parent species for both
C. neomexicanus
and
C. tesselatus
. Furthermore, these data imply that these two parthenogenetic species are younger than some races of
C. tigris
.
Distribution of Transmembrane Polypeptides in Freeze Fracture
Authors: Edwards Harold H. , Mueller Thomas J. , Morrison Martin
Published: October 2006

Human erythrocytes have been freeze-fractured, and the polypeptides associated with the separate halves of the membrane bilayer have been analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The transmembrane proteins were differentially separated by the fracture process. Although sialoglycoproteins associated with the outer half of the membrane, the anion transport protein (band 3) mainly remained with the inner half of the membrane. Well-defined fragments of the sialoglycoproteins were produced by the freeze-fracture procedure, indicating that selected covalent bonds of these transmembrane proteins were broken.
Antibody-Selective Membrane Electrodes
Authors: Solsky R. L. , Rechnitz G. A.
Published: October 2006

Direct antibody-sensing membrane electrodes have been developed by immobilizing ion-carrier immunogen conjugates in a liquid membrane matrix. The resulting potentiometric probes measure specific antibodies with high selectivity over nonspecific antibodies in the physiological
p
H range. The electrode response is shown to arise from the selective interaction of the antibody with the membrane-bound immunogen.
Perception of Echo Phase Information in Bat Sonar
Authors: Simmons James A.
Published: October 2006

Echolocating bats (
Eptesicus fuscus
) can detect changes as small as 500 nanoseconds in the arrival time of sonar echoes when these changes appear as jitter or alternations in arrival time from one echo to the next. The psychophysical function relating the bat's performance to the magnitude of the jitter corresponds to the half-wave rectified cross-correlation function between the emitted sonar signals and the echoes. The bat perceives the phase or period structure of the sounds, which cover the 25- to 100-kilohertz frequency range, as these are represented in the auditory system after peripheral transformation. The acoustic image of a sonar target is apparently derived from time-domain or periodicity information processing by the nervous system.
Regulation of Gene Expression: Possible Role of Repetitive Sequences
Authors: Davidson Eric H. , Britten Roy J.
Published: October 2006

Large contrasts are observed between the messenger RNA populations of different tissues and of embryos at different stages of development. Nevertheless, coding sequences for genes not expressed in a cell appear to be present in its nuclear RNA. Though many nuclear RNA transcripts of single copy DNA sequences are held in common between tissues, an additional set, probably consisting of non-message sequences, is not shared. Nuclear RNA also contains transcripts of repetitive DNA sequences. Certain repeat families are represented at high levels in the nuclear RNA of particular tissues and much lower levels in others. It is surprising that both complements of most repeat sequences are present in nuclear RNA. These observations lead to a model for regulation of gene expression in which the formation of repetitive RNA-RNA duplexes controls the production of messenger RNA.
Erythrosin B Inhibits Dopamine Transport in Rat Caudate Synaptosomes
Authors: Lafferman Jeffrey A. , Silbergeld Ellen K.
Published: October 2006

Erythrosin B is a member of a class of fluorescein dyes that are suggested to elicit hyperkinesis when ingested by susceptible children. We found that erythrosin B inhibits dopamine uptake in rat caudate synaptosomes "uncompetitively" in the 10- to 800-micromolar range. Half maximal inhibition of uptake occurred at 45 micromolar. Uncompetitive inhibition denotes a decrease in efficacy of the dopamine membrane transport mechanism with an increase in affinity of dopamine to the carrier. Erythrosin B also decreased nonsaturable binding of dopamine to the synaptosome membrane. The inhibitory action of erythrosin B on dopamine uptake is consistent with the hypothesis that erythrosin B can act as a central excitatory agent able to induce hyperkinetic behavior.
Reversal Potential for Noradrenaline-Induced Hyperpolarization of Spinal Motoneurons
Authors: Marshall Kenneth C. , Engberg Ingemar
Published: October 2006

By using two separate electrodes with tips inside a single feline motoneuron, current-voltage characteristics were studied during extracellular iontophoresis of noradrenaline. The usually observed hyperpolarization was accompanied by an increase in membrane resistance and became larger with polarizing and smaller with depolarizing currents. During large depolarizing current injections, the noradrenaline-induced potential reversed its direction, usually at a membrane potential of about -20 millivolts. These data are compatible with the concept that noradrenaline hyperpolarizes nerve cells by decreasing resting membrane conductances to sodium and potassium ions. The observation could also be explained by a nonspecific decrease in ion permeability that is associated with a hyperpolarization due to sodium pump activation.
The Rôle of the Nucleus in Oxidation
Authors: Osterhout W. J. V.
Published: October 2006

Injury produces in the leaf-cells of the Indian Pipe (
Monotropa uniflora
) a darkening which is due to oxidation. The oxidation is much more rapid in the nucleus than in the cytoplasm and the facts indicate that this is also the case with the oxidation of the uninjured cell.
4-Aminobutyrate:2-Oxoglutarate Aminotransferase in Blood Platelets
Authors: White Helen L.
Published: October 2006

Platelet lysates obtained from blood of humans, dogs, and rats catalyzed the transamination of 4-aminobutyrate with 2-oxoglutarate as cosubstrate. Human platelet 4-aminobutyrate:2-oxoglutarate aminotransferase (36.5 ± 3.2 picomoles per minute per milligram of platelet protein) resembled the brain enzyme in kinetic properties and in response to cofactors and inhibitors.
Drug Discrimination Training with Progressively Lowered Doses
Authors: Overton Donald A.
Published: October 2006

Rats were trained to discriminate drug from no-drug conditions in a two-lever operant task. Moderately high dosages were used initially. Whenever the discrimination was learned, training was continued with progressively reduced dosages. Eventually the rats discriminated extremely low doses of phenobarbital, chlordiazepoxide, cyclazocine, and fentanyl.