bluuebunny/crossref_metadata_2025 huggingface dataset:
Model of the Origin of Rhythmic Population Oscillations in the Hippocampal Slice
Authors: Traub Roger D. , Miles Richard , Wong Robert K. S.
Published: October 2006

One goal of mammalian neurobiology is to understand the generation of neuronal activity in large networks. Conceptual schemes have been based on either the properties of single cells or of individual synapses. For instance, the intrinsic oscillatory properties of individual thalamic neurons are thought to underlie thalamic spindle rhythms. This issue has been pursued with a computer model of the CA3 region of the hippocampus that is based on known cellular and synaptic properties. Over a wide range of parameters, this model generates a rhythmic activity at a frequency faster than the firing of individual cells. During each rhythmic event, a few cells fire while most other cells receive synchronous synaptic inputs. This activity resembles the hippocampal theta rhythm as well as synchronized synaptic events observed in vitro. The amplitude and frequency of this emergent rhythmic activity depend on intrinsic cellular properties and the connectivity and strength of both excitatory and inhibitory synapses.
RNA-Protein Interactions in 30
S
Ribosomal Subunits: Folding and Function of 16
S
rRNA
Authors: Stern Seth , Powers Ted , Changchien Li-Ming , Noller Harry F.
Published: October 2006

Chemical probing methods have been used to "footprint" 16
S
ribosomal RNA (rRNA) at each step during the in vitro assembly of twenty 30
S
subunit ribosomal proteins. These experiments yield information about the location of each protein relative to the structure of 16
S
rRNA and provide the basis for derivation of a detailed model for the three-dimensional folding of 16
S
rRNA. Several lines of evidence suggest that protein-dependent conformational changes in 16
S
rRNA play an important part in the cooperativity of ribosome assembly and in fine-tuning of the conformation and dynamics of 16
S
rRNA in the 30
S
subunit.
Progress Toward Human Gene Therapy
Authors: Friedmann Theodore
Published: October 2006

Current therapies for most human genetic diseases are inadequate. In response to the need for effective treatments, modern molecular genetics is providing tools for an unprecedented new approach to disease treatment through an attack directly on mutant genes. Recent results with several target organs and gene transfer techniques have led to broad medical and scientific acceptance of the feasibility of this "gene therapy" concept for disorders of the bone marrow, liver, and central nervous system; some kinds of cancer; and deficiencies of circulating enzymes, hormones, and coagulation factors. The most well-developed models involve alteration of mutant target genes by gene transfer with recombinant pathogenic viruses in order to express new genetic information and to correct disease phenotypes--the conversion of the swords of pathology into the plowshares of therapy.
Pathological Changes Induced in Cerebrocortical Neurons by Phencyclidine and Related Drugs
Authors: Olney John W. , Labruyere Joann , Price Madelon T.
Published: October 2006

Phencyclidine (PCP), a dissociative anesthetic and widely abused psychotomimetic drug, and MK-801, a potent PCP receptor ligand, have neuroprotective properties stemming from their ability to antagonize the excitotoxic actions of endogenous excitatory amino acids such as glutamate and aspartate. There is growing interest in the potential application of these compounds in the treatment of neurological disorders. However, there is an apparent neurotoxic effect of PCP and related agents (MK-801, tiletamine, and ketamine), which has heretofore been overlooked: these drugs induce acute pathomorphological changes in specific populations of brain neurons when administered subcutaneously to adult rats in relatively low doses. These findings raise new questions regarding the safety of these agents in the clinical management of neurodegenerative diseases and reinforce concerns about the potential risks associated with illicit use of PCP.
Bright Light Induction of Strong (Type 0) Resetting of the Human Circadian Pacemaker
Authors: Czeisler Charles A. , Kronauer Richard E. , Allan James S. , Duffy Jeanne F. , Jewett Megan E. , Brown Emery N. , Ronda Joseph M.
Published: October 2006

The response of the human circadian pacemaker to light was measured in 45 resetting trials. Each trial consisted of an initial endogenous circadian phase assessment, a three-cycle stimulus which included 5 hours of bright light per cycle, and a final phase assessment. The stimulus induced strong (type 0) resetting, with responses highly dependent on the initial circadian phase of light exposure. The magnitude and direction of the phase shifts were modulated by the timing of exposure to ordinary room light, previously thought to be undetectable by the human pacemaker. The data indicate that the sensitivity of the human circadian pacemaker to light is far greater than previously recognized and have important implications for the therapeutic use of light in the management of disorders of circadian regulation.
Adipsin and Complement Factor D Activity: An Immune-Related Defect in Obesity
Authors: Rosen Barry S. , Cook Kathleen S. , Yaglom Julia , Groves Douglas L. , Volanakis John E. , Damm Deborah , White Tyler , Spiegelman Bruce M.
Published: October 2006

Adipsin is a serine protease that is secreted by adipocytes into the bloodstream; it is deficient in several animal models of obesity, representing a striking example of defective gene expression in this disorder. Recombinant mouse adipsin was purified and its biochemical and enzymatic properties were studied in order to elucidate the function of this protein. Activated adipsin has little or no proteolytic activity toward most substrates but has the same activity as human complement factor D, cleaving complement factor B when it is complexed with activated complement component C3. Like authentic factor D, adipsin can activate the alternative pathway of complement, resulting in red blood cell lysis. Decreased (58 to 80 percent) complement factor D activity, relative to lean controls, was observed as a common feature of several experimental models of obesity, including the
ob
/
ob
,
db
/
db
, and monosodium glutamate (MSG)-injected mouse and the
fa
/
fa
rat. These results suggest that adipsin and the alternative pathway of complement may play an unexpected but important role in the regulation of systemic energy balance in vivo.
The Periaqueductal Gray Matter Mediates Opiate-Induced Immunosuppression
Authors: Weber Richard J. , Pert Agu
Published: October 2006

The periaqueductal gray matter of the mesencephalon (PAG) subserves a variety of diverse autonomic functions and also appears to be a site for opiate action in the induction of immunosuppression. Microinjections of morphine into the PAG, but not into other opiate receptor-containing neuroanatomical sites, result in a rapid suppression of natural killer (NK) cell activity. The NK cell suppression can be blocked by prior peripheral administration of the opiate antagonist naltrexone. These findings demonstrate that certain central actions of opiates that produce changes in NK cell function are mediated through opiate receptors in the PAG and identify a brain region involved in opiate regulation of immune function.
Contingent Genetic Regulatory Events in T Lymphocyte Activation
Authors: Crabtree Gerald R.
Published: October 2006

Interaction of antigen in the proper histocompatibility context with the T lymphocyte antigen receptor leads to an orderly series of events resulting in morphologic change, proliferation, and the acquisition of immunologic function. In most T lymphocytes two signals are required to initiate this process, one supplied by the antigen receptor and the other by accessory cells or agents that activate protein kinase C. Recently, DNA sequences have been identified that act as response elements for one or the other of the two signals, but do not respond to both signals. The fact that these sequences lie within the control regions of the same genes suggests that signals originating from separate cell membrane receptors are integrated at the level of the responsive gene. The view is put forth that these signals initiate a contingent series of gene activations that bring about proliferation and impart immunologic function.
Tonotopic Organization of the Auditory Cortex: Pitch Versus Frequency Representation
Authors: Pantev C.. , Hoke M.. , Lütkenhöner B.. , Lehnertz K..
Published: October 2006

According to the place principles of the classical hearing theory, the physical entity frequency is encoded in the auditory periphery as place information (tonotopic representation), which is decoded in more central parts of the auditory system to form the subjective entity pitch. However, this relation is true only for pure-tone signals (spectral pitch); it can be quite different in the case of complex auditory stimuli (virtual pitch), thus requiring a multistage process for pitch formation. Neuromagnetic measurements showed that the tonotopic organization of the primary auditory cortex reflects the pitch rather than the frequency of the stimulus; that is, the pitch formation process must take place in subcortical regions.
Pancreatic Neoplasia Induced by SV40 T-Antigen Expression in Acinar Cells of Transgenic Mice
Authors: Ornitz David M. , Hammer Robert E. , Messing Albee , Palmiter Richard D. , Brinster Ralph L.
Published: October 2006

Three lines of transgenic mice were produced that develop pancreatic neoplasms as a consequence of expression of an elastase I-SV40 T-antigen fusion gene in the acinar cells. A developmental analysis suggests at least a two-stage process in the ontogeny of this disease. The first stage is a T antigen-induced, preneoplastic state characterized by a progression from hyperplasia to dysplasia of the exocrine pancreas, by an increased percentage of tetraploid cells, and by an arrest in acinar cell differentiation. The second stage is characterized by the formation of tumor nodules that appear to be monoclonal, because they have discrete aneuploid DNA contents. The cells within the nodules as compared to normal pancreatic tissue have less total RNA by a factor of 5, less pancreas-specific messenger RNA by a factor of about 50, and increased levels of T-antigen messenger RNA. A tumor cell line has been derived that retains both pancreatic and neoplastic properties.
New Perspectives in Cell Adhesion: RGD and Integrins
Authors: Ruoslahti Erkki , Pierschbacher Michael D.
Published: October 2006

Rapid progress has been made in the understanding of the molecular interactions that result in cell adhesion. Many adhesive proteins present in extracellular matrices and in the blood contain the tripeptide arginine-glycine-aspartic acid (RGD) as their cell recognition site. These proteins include fibronectin, vitronectin, osteopontin, collagens, thrombospondin, fibrinogen, and von Willebrand factor. The RGD sequences of each of the adhesive proteins are recognized by at least one member of a family of structurally related receptors, integrins, which are heterodimeric proteins with two membrane-spanning subunits. Some of these receptors bind to the RGD sequence of a single adhesion protein only, whereas others recognize groups of them. The conformation of the RGD sequence in the individual proteins may be critical to this recognition specificity. On the cytoplasmic side of the plasma membrane, the receptors connect the extracellular matrix to the cytoskeleton. More than ten proved or suspected RGD-containing adhesion-promoting proteins have already been identified, and the integrin family includes at least as many receptors recognizing these proteins. Together, the adhesion proteins and their receptors constitute a versatile recognition system providing cells with anchorage, traction for migration, and signals for polarity, position, differentiation, and possibly growth.
Cloning, Sequencing, and Expression of the Gene Coding for the Human Platelet α
2
-Adrenergic Receptor
Authors: Kobilka B. K. , Matsui H. , Kobilka T. S. , Yang-Feng T. L. , Francke U. , Caron M. G. , Lefkowitz R. J. , Regan J. W.
Published: October 2006

The gene for the human platelet α
2
-adrenergic receptor has been cloned with oligonucleotides corresponding to the partial amino acid sequence of the purified receptor. The identity of this gene has been confirmed by the binding of α
2
-adrenergic ligands to the cloned receptor expressed in
Xenopus laevis
oocytes. The deduced amino acid sequence is most similar to the recently cloned human β
2
- and β
1
-adrenergic receptors; however, similarities to the muscarinic cholinergic receptors are also evident. Two related genes have been identified by low stringency Southern blot analysis. These genes may represent additional α
2
-adrenergic receptor subtypes.
Chimeric α
2
-,β
2
-Adrenergic Receptors: Delineation of Domains Involved in Effector Coupling and Ligand Binding Specificity
Authors: Kobilka Brian K. , Kobilka Tong Sun , Daniel Kiefer , Regan John W. , Caron Marc G. , Lefkowitz Robert J.
Published: October 2006

The α
2
and β
2
adrenergic receptors, both of which are activated by epinephrine, but which can be differentiated by selective drugs, have opposite effects (inhibitory and stimulatory) on the adenylyl cyclase system. The two receptors are homologous with each other, rhodopsin, and other receptors coupled to guanine nucleotide regulatory proteins and they contain seven hydrophobic domains, which may represent transmembrane spanning segments. The function of specific structural domains of these receptors was determined after construction and expression of a series of chimeric α
2
-,β
2
-adrenergic receptor genes. The specificity for coupling to the stimulatory guanine nucleotide regulatory protein lies within a region extending from the amino terminus of the fifth hydrophobic domain to the carboxyl terminus of the sixth. Major determinants of α
2
- and β
2
-adrenergic receptor agonist and antagonist ligand binding specificity are contained within the seventh membrane spanning domain. Chimeric receptors should prove useful for elucidating the structural basis of receptor function.
Brain Barrier Tissues: End Organs for Atriopeptins
Authors: Steardo Luca , Nathanson James A.
Published: October 2006

Little is known about the pathophysiology of cerebral edema and other disturbances of water balance that involve the barrier tissues at the interface of blood and brain. The present experiments show that these barrier tissues contain receptors and second messenger systems for atriopeptins, recently identified cardiac peptides involved in peripheral water regulation. They also show that atriopeptins can alter the rate of cerebrospinal fluid production. Because the blood-brain and blood-cerebrospinal fluid barriers are involved in normal water movements in the central nervous system, these studies suggest that brain barrier tissues may be important end organs for the atriopeptins and that atriopeptins could have therapeutic application to disorders of water balance in the central nervous system. An isolated, purified population of atriopeptin receptor cells, obtained from choroid epithelium, was used in these experiments. This cell population may provide a valuable model system for investigating the intracellular biochemical mechanisms through which atriopeptins exert their actions.
Cellular and Molecular Mechanisms of Drug Dependence
Authors: Koob George F. , Bloom Floyd E.
Published: October 2006

The molecular and cellular actions of three classes of abused drugs—opiates, psychostimulants, and ethanol—are reviewed in the context of behavioral studies of drug dependence. The immediate effects of drugs are compared to those observed after long-term exposure. A neurobiological basis for drug dependence is proposed from the linkage between the cellular and behavioral effects of these drugs.
Structural Origins of High-Affinity Biotin Binding to Streptavidin
Authors: Weber Patricia C. , Ohlendorf D. H. , Wendoloski J. J. , Salemme F. R.
Published: October 2006

The high affinity of the noncovalent interaction between biotin and streptavidin forms the basis for many diagnostic assays that require the formation of an irreversible and specific linkage between biological macromolecules. Comparison of the refined crystal structures of apo and a streptavidin:biotin complex shows that the high affinity results from several factors. These factors include the formation of multiple hydrogen bonds and van der Waals interactions between biotin and the protein, together with the ordering of surface polypeptide loops that bury the biotin in the protein interior. Structural alterations at the biotin binding site produce quaternary changes in the streptavidin tetramer. These changes apparently propagate through cooperative deformations in the twisted β sheets that link tetramer subunits.
Selective Loss of Hippocampal Granule Cells in the Mature Rat Brain After Adrenalectomy
Authors: Sloviter Robert S. , Valiquette Guy , Abrams Gary M. , Ronk Edward C. , Sollas Anne L. , Paul Linda A. , Neubort Simon
Published: October 2006

Adrenalectomy of adult male rats resulted in a nearly complete loss of hippocampal granule cells 3 to 4 months after surgery. Nissl and immunocytochemical staining of hippocampal neurons revealed that the granule cell loss was selective; there was no apparent loss of hippocampal pyramidal cells or of γ-amino butyric acid (GABA)-, somatostatin-, neuropeptide Y-, calcium binding protein-, or parvalbumin-containing hippocampal interneurons. The hippocampal CA1 pyramidal cells of adrenalectomized animals exhibited normal electrophysiological responses to afferent stimulation, whereas responses evoked in the dentate gyrus were severely attenuated. Corticosterone replacement prevented both the adrenalectomy-induced granule cell loss and the attenuated physiological response. Thus, the adrenal glands play a role in maintaining the structural integrity of the normal adult brain.
Free Calcium at Rest During "Catch" in Single Smooth Muscle Cells
Authors: Ishii N. , Simpson A. W. , Ashley C. C.
Published: October 2006

Tension and intracellular free calcium concentration ([Ca
2+
]
i
) were measured simultaneously in single smooth muscle cells isolated from the anterior byssus retractor muscle (ABRM) of
Mytilus edulis
that were loaded with the fluorescent Ca
2+
indicator fura-2. Electrical stimulation evoked a transient elevation of [Ca
2+
]
i
associated with a "catch" contraction. During the catch state, however, [Ca
2+
]
i
was effectively at its resting level and was unaffected by 5-hydroxytryptamine, which induced a rapid relaxation from catch. The results indicate that a maintained high [Ca
2+
]
i
is not required for the maintenance of catch tension in intact ABRM and that there was no significant change in [Ca
2+
]
i
upon abolition of catch.
Generalized Tube Model of Biased Reptation for Gel Electrophoresis of DNA
Authors: Noolandi Jaan , Slater Gary W. , Lim Hwa Aun , Viovy Jean Louis
Published: October 2006

A theoretical analysis of the reptational motion of DNA in a gel that includes the effects of molecular fluctuations has been used to explain the main features found in experiments involving periodic inversion of the electric field. The resonance-like decrease of the electrophoretic mobility as a function of pulse duration is related to transient "undershoots" in the orientation of the molecule, in agreement with recent experimental data. These features arise from a delicate interplay of internal and center of mass motion of the molecules under pulsed field conditions, and are important for the separation of DNA molecules in the size range 0.2 to 10 million base pairs.
Binocular Unmasking: An Analog to Binaural Unmasking?
Authors: Schneider Bruce , Moraglia Giampaolo , Jepson Allan
Published: October 2006

A visual analog to binaural unmasking was explored. The observer's task was to detect, under stereoscopic viewing conditions, an apertured sinusoidal grating added to a square patch of visual noise. In the experimental condition, the square patch of noise was presented within a frame such that the right-eye noise was a shifted version of the left-eye noise. Because of the disparity in the noise images, subjects perceived, under stereoscopic viewing conditions, that the noise patch was located behind the frame. When sinusoidal signals were added to this noise patch, the signals were clearly more detectable when the signal disparity was zero than when the signal disparity equaled that of the noise patch, demonstrating the existence of visual unmasking. Hence, under appropriate circumstances, binocular processing, in addition to providing information about depth, can also enhance the detectability of visual patterns.
Prevention of Rapid Intracellular Degradation of ODC by a Carboxyl-Terminal Truncation
Authors: Ghoda L. , van Daalen Wetters T. , Macrae M. , Ascherman D. , Coffino P.
Published: October 2006

Ornithine decarboxylase (ODC) was converted from a protein with a short intracellular half-life in mammalian cells to a stable protein by truncating 37 residues at its carboxyl terminus. Cells expressing wild-type protein lost ODC activity with a half-life of approximately 1 hour. Cells expressing the truncated protein, however, retained full activity for at least 4 hours. Pulse-chase experiments in which immunoprecipitation and gel electrophoresis were used confirmed the stabilizing effect of the truncation. Thus, a carboxyl-terminal domain is responsible for the rapid intracellular degradation of murine ODC.
Atrial Natriuretic Peptide Elevation in Congestive Heart Failure in the Human
Authors: Burnett J. C. , Kao P. C. , Hu D. C. , Heser D. W. , Heublein D. , Granger J. P. , Opgenorth T. J. , Reeder G. S.
Published: October 2006

A sensitive radioimmunoassay for atrial natriuretic peptide was used to examine the relation between circulating atrial natriuretic peptide and cardiac filling pressure in normal human subjects, in patients with cardiovascular disease and normal cardiac filling pressure, and in patients with cardiovascular disease and elevated cardiac filling pressure with and without congestive heart failure. The present studies establish a normal range for atrial natriuretic peptide in normal human subjects. These studies also establish that elevated cardiac filling pressure is associated with increased circulating concentrations of atrial natriuretic peptide and that congestive heart failure is not characterized by a deficiency in atrial natriuretic peptide, but with its elevation.
Molecular Genetics of Human Color Vision: The Genes Encoding Blue, Green, and Red Pigments
Authors: Nathans Jeremy , Thomas Darcy , Hogness David S.
Published: October 2006

Human color vision is based on three light-sensitive pigments. The isolation and sequencing of genomic and complementary DNA clones that encode the apoproteins of these three pigments are described. The deduced amino acid sequences show 41 ± 1 percent identity with rhodopsin. The red and green pigments show 96 percent mutual identity but only 43 percent identity with the blue pigment. Green pigment genes vary in number among color-normal individuals and, together with a single red pigment gene, are proposed to reside in a head-to-tail tandem array within the X chromosome.
Skeletal Muscle as the Potential Power Source for a Cardiovascular Pump: Assessment in Vivo
Authors: Acker Michael A. , Hammond Robert L. , Mannion John D. , Salmons Stanley , Stephenson Larry W.
Published: October 2006

Skeletal muscle ventricles (SMVs) were constructed from canine latissimus dorsi and connected to a totally implantable mock circulation device. The SMVs, stimulated by an implantable pulse generator, pumped continuously for up to 8 weeks in free-running beagle dogs. Systolic pressures produced by the SMVs, initially of 139 ± 7.2 mmHg and after 1 month of continuous pumping of 107 ± 7 mmHg, were comparable to normal physiologic pressures in the adult beagles (114 ± 21 mmHg). After 2 weeks of continuous pumping, the mean stroke work of the SMVs was 0.4 × 10
6
ergs, a performance that compares favorably with the animal's cardiac ventricles. This study shows that canine skeletal muscle which has not received prior training or electrical conditioning can perform sustained work at the high levels needed for an auxiliary cardiovascular pump. It might be possible eventually to use such muscle pumps in humans to assist the failing circulation and to provide support in children with certain types of congenital heart defects.
YIGSR, a Synthetic Laminin Pentapeptide, Inhibits Experimental Metastasis Formation
Authors: Iwamoto Yukihide , Robey Frank A. , Graf Jeannette , Sasaki Makoto , Kleinman Hynda K. , Yamada Yoshihiko , Martin George R.
Published: October 2006

The invasion of tumor cells through basement membranes is a critical step in the formation of metastases. The binding of the malignant cells to laminin in the basement membranes allows their attachment and activates their invasiveness. Recently a synthetic nonapeptide from the B1 chain sequence of laminin was identified as a major site for cell binding. A pentapeptide within the nonapeptide sequence was found to reduce the formation of lung colonies in mice injected with melanoma cells and also to inhibit the invasiveness of the cells in vitro.
Atrial Natriuretic Factor-SV40 T Antigen Transgenes Produce Tumors and Cardiac Arrhythmias in Mice
Authors: Field Loren J.
Published: October 2006

Transgenic mice that carry fusions between the transcriptional regulatory sequences of atrial natriuretic factor (a hormone intimately involved in the regulation of blood pressure) and those encoding SV40 T antigen (an oncoprotein) were generated. Although both atria express the fusion gene, the pathological response to T antigen is asymmetrical. The right atrium undergoes a several hundredfold increase in mass while the left atrium remains relatively normal in size. Hyperplasia is accompanied by a progressive increase in both the frequency and severity of abnormalities in the atrial conduction system, which ultimately result in death.
Reexamination of Glucose-6-Phosphatase Activity in the Brain in Vivo: No Evidence for a Futile Cycle
Authors: Nelson Thomas , Lucignani Giovanni , Atlas Steven , Crane Alison M. , Dienel Gerald A. , Sokoloff Louis
Published: October 2006

Glucose-6-phosphatase activity in the rat brain in vivo was estimated by measuring the differential loss of tritium and carbon-14 from the glucose pool labeled by a mixture of [2-
3
H]glucose and [U-
14
C]glucose. The results provide no evidence of significant dephosphorylation of glucose-6-phosphate and do not support the hypothesis of a futile cycle involving glucose-6-phosphatase activity in the brain.
Vasopressin-Stimulated Release of Atriopeptin: Endocrine Antagonists in Fluid Homeostasis
Authors: Manning Pamela T. , Schwartz David , Katsube Nobuo C. , Holmberg Sandra W. , Needleman Philip
Published: October 2006

Administration of pharmacological doses of arginine-vasopressin, related peptides, and other pressor agents induced a profound release of atriopeptin immunoreactivity into the circulation. The stimulated release of atriopeptin apparently was related to increased arterial blood pressure. Neither the nonpressor vasopressin analog 1-deamino-D-Arg
8
-vasopressin nor arginine-vasopressin in the presence of a specific pressor antagonist caused atriopeptin to be released into the circulation. Urine output was correlated with the level of atriopeptin released. Physiological levels of arginine-vasopressin suppress diuresis and produced vasoconstriction. Pharmacological levels of the hormone stimulated the cardiac endocrine system to release atriopeptin, which may cause diuresis and vasodilation to physiologically antagonize the effects of vasopressin.
Amplification of a Novel v-
erb
B-Related Gene in a Human Mammary Carcinoma
Authors: King C. Richter , Kraus Matthias H. , Aaronson Stuart A.
Published: October 2006

The cellular gene encoding the receptor for epidermal growth factor (EGF) has considerable homology to the oncogene of avian erythroblastosis virus. In a human mammary carcinoma, a DNA sequence was identified that is related to v-
erb
B but amplified in a manner that appeared to distinguish it from the gene for the EGF receptor. Molecular cloning of this DNA segment and nucleotide sequence analysis revealed the presence of two putative exons in a DNA segment whose predicted amino acid sequence was closely related to, but different from, the corresponding sequence of the
erb
B/EGF receptor. Moreover, this DNA segment identified a 5-kilobase transcript distinct from the transcripts of the EGF receptor gene. Thus, a new member of the tyrosine kinase proto-oncogene family has been identified on the basis of its amplification in a human mammary carcinoma.
Enzymatic Amplification of β-Globin Genomic Sequences and Restriction Site Analysis for Diagnosis of Sickle Cell Anemia
Authors: Saiki Randall K. , Scharf Stephen , Faloona Fred , Mullis Kary B. , Horn Glenn T. , Erlich Henry A. , Arnheim Norman
Published: October 2006

Two new methods were used to establish a rapid and highly sensitive prenatal diagnostic test for sickle cell anemia. The first involves the primer-mediated enzymatic amplification of specific β-globin target sequences in genomic DNA, resulting in the exponential increase (220,000 times) of target DNA copies. In the second technique, the presence of the β
A
and β
S
alleles is determined by restriction endonuclease digestion of an end-labeled oligonucleotide probe hybridized in solution to the amplified β-globin sequences. The β-globin genotype can be determined in less than 1 day on samples containing significantly less than 1 microgram of genomic DNA.
Motion Sickness: An Evolutionary Hypothesis
Authors: Treisman Michel
Published: October 2006

Since the occurrence of vomiting as a response to motion is both widespread and apparently disadvantageous, it presents a problem for evolutionary theory. An hypothesis is proposed suggesting that motion sickness is triggered by difficulties which arise in the programming of movements of the eyes or head when the relations between the spatial frameworks defined by the visual, vestibular, or proprioceptive inputs are repeatedly and unpredictably perturbed. Such perturbations may be produced by certain types of motion, or by disturbances in sensory input or motor control produced by ingested toxins. The last would be the important cause in nature, the main function of the emesis being to rid the individual of ingested neurotoxins. Its occurrence in response to motion would be an accidental byproduct of this system.
Immortalization of Human T Lymphocytes After Transfection of Epstein-Barr Virus DNA
Authors: Stevenson Mario , Volsky Barbara , Hedenskog Mona , Volsky David J.
Published: October 2006

Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, has the ability to transform human B lymphocytes. No other cell type has been experimentally transformed by EBV, either by intact virions or naked viral DNA and subgenomic fragments. Two immortalized human T-lymphoblastoid cell lines have now been established by transfecting cord blood lymphocytes with purified B95-8 viral DNA enclosed in fusogenic Sendai virus envelopes (RSVE) and then exposing the cells to EBV from a P3HR-1 cell subclone. One of these lines, which has been fully characterized, is termed HBD-1. This line is positive for EBV DNA and expresses surface OKT11, OKT4, and Tac receptors, but not M-1, μ immunoglobulin chains, EBV receptors, or B-1 surface markers. The cells contain fully rearranged T-cell receptor genes and germline immunoglobulin genes. The karyotype of the cells is normal, they do not require interleukin-2 for growth, and do not contain human T-lymphotropic virus type I. However, the HBD-1 cells contain incomplete EBV genomes and express several EBV-determined antigens, including the early antigen type D, membrane antigens, but not EBV-determined nuclear antigen (EBNA). This association of the EBV genome with permanently growing hematopoietic cells of non B-cell lineage should prove useful in studies on the mechanism of EBV-mediated cell transformation.
Induction of Suppressor T Cells in Systemic Lupus Erythematosus by Thymosin and Cultured Thymic Epithelium
Authors: Horowitz Sheldon , Borcherding Wayne , Moorthy A. Vishnu , Chesney Russell , Schulte-Wisserman Hermann , Hong Richard , Goldstein Allan
Published: October 2006

Patients with systemic lupus erythematosus lacked suppressor T cell function. Suppressor cell activity was induced in cells from many of these patients by incubation with thymosin or cultured thymic epithelium. These results suggest that thymic manipulation may be a useful therapeutic modality in this disease.
Two Avirulent Herpes Simplex Viruses Generate Lethal Recombinants in Vivo
Authors: Javier R. T. , Sedarati F. , Stevens J. G.
Published: October 2006

While it is widely appreciated that infection with a virulent virus can produce disease in an animal, the ability of a mixture of avirulent viruses to produce disease by means of complementation or recombination in vivo has not been established. In this study, two weakly neuroinvasive herpes simplex virus type 1 (HSV-1) strains were simultaneously inoculated onto the footpads of mice. Many (62%) of the animals that received a 1:1 mixture of the viruses died, whereas the animals that received a similar or 100-fold higher dose of each agent alone survived. Of fourteen viruses isolated from the brains of ten mice that died after receiving the mixture of the two weakly neuroinvasive viruses, eleven were recombinants; three of these recombinants were lethal when reapplied to the footpads of mice. These results show that two avirulent HSV-1 variants may interact in vivo to produce virulent recombinants and a lethal infection. They also suggest that different genetic lesions account for the weakly neuroinvasive character of the HSV-1 strains ANG and KOS after footpad inoculation.
Human T-Lymphotropic Virus Type 4 and the Human Immunodeficiency Virus in West Africa
Authors: Kanki Phyllis J. , M'Boup Souleymane , Ricard Dominique , Barin Francis , Denis François , Boye Chiekh , Sangare Lasana , Travers Karin , Albaum Michael , Marlink Richard , Romet-Lemonne Jean-Loup , Essex Myron
Published: October 2006

A new human T-lymphotropic virus (HTLV-4) was recently described in healthy people from Senegal. This virus has many properties in common with members of the human T-lymphotropic viruses, particularly the human immunodeficiency virus or HIV, the etiologic agent of acquired immune deficiency syndrome (AIDS), but does not appear to be associated with immunodeficiency-related disorders. In the present study, serum samples were obtained from 4248 individuals from six West African countries, including Senegal, Guinea, Guinea Bissau, Mauritania, Burkina Faso, and Ivory Coast. These samples, collected during 1985-1987, were from people categorized as healthy control, sexually active risk, and disease populations. All samples were analyzed for reactivity to HTLV-4 and HIV by radioimmunoprecipitation-sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Evidence for HTLV-4 infection was found in five of the six countries. The seroprevalence varied markedly from country to country. Healthy sexually active individuals in the risk category had the highest levels of HTLV-4 infection compared to individuals in the healthy control category and the disease category, the latter including AIDS patients. The seroprevalence of HIV infection in most of these countries was quite low, although tightly associated with the rare cases of AIDS. The biology of HTLV-4 infection thus differs from that of HIV in Central Africa or the United States and Europe. The presence of these viruses and their different pathogenicities in several countries of West Africa indicate the necessity for serologic assays that will distinguish between them. Further studies of their origin and distribution as well as of their biology will be important in advancing our understanding of AIDS.
A Physiological Basis for a Theory of Synapse Modification
Authors: Bear Mark F. , Cooper Leon N. , Ebner Ford F.
Published: October 2006

The functional organization of the cerebral cortex is modified dramatically by sensory experience during early postnatal life. The basis for these modifications is a type of synaptic plasticity that may also contribute to some forms of adult learning. The question of how synapses modify according to experience has been approached by determining theoretically what is required of a modification mechanism to account for the available experimental data in the developing visual cortex. The resulting theory states precisely how certain variables might influence synaptic modifications. This insight has led to the development of a biologically plausible molecular model for synapse modification in the cerebral cortex.
Genetic Evidence for Transmembrane Acetylation by Lysosomes
Authors: Bame Karen J. , Rome Leonard H.
Published: October 2006

Acetyl-CoA:α-glucosaminide
N
-acetyltransferase is a lysosomal-membrane enzyme deficient in a genetic disorder, Sanfilippo disease type C. The enzyme catalyzes the transfer of an acetyl group from cytoplasmic acetyl-coenzyme A (acetyl-CoA) to terminal α-glucosamine residues of heparan sulfate within the organelle. Previous kinetic experiments indicated that the enzyme carries out a transmembrane acetylation via a ping-pong mechanism; the reaction can therefore be dissected into two half reactions—acetylation of the enzyme, and transfer of the acetyl group to glucosamine. Cells derived from patients were found to differ in their ability to perform each half reaction. Five cell lines (derived from three families) were able to catalyze acetylation of the lysosomal membrane and to carry out acetyl-CoA/CoA exchange, whereas a sixth cell line was devoid of this activity.
Human Lymphocytes Making Rheumatoid Factor and Antibody to ssDNA Belong to Leu-1
+
B-Cell Subset
Authors: Casali Paolo , Burastero Samuele .E , Nakamura Minoru , Inghirami Giorgio , Notkins Abner Louis
Published: October 2006

B lymphocytes bearing the Leu-1 cell-surface antigen (Leu-1
+
), the human equivalent of mouse Ly-1
+
B lymphocytes, have been detected in human peripheral blood, but there is little information on their frequency and properties. Analysis by fluorescence-activated cell sorter and double immunofluorescence showed that Leu-1
+
B cells are consistently present in the peripheral blood and spleens of healthy subjects and constitute 17.0 ± 5.0% (mean value ± standard deviation) and 17.3 ± 3.9%, respectively, of total B cells. When purified Leu-1
+
and Leu-1
-
B lymphocytes were transformed into immunoglobulin-secreting cells by infection with Epstein-Barr virus and the culture fluids were tested for reactivity with self-antigens, at least two important autoantibodies, antibody to the Fc fragment of human immunoglobulin G (rheumatoid factor) and antibody to single-stranded DNA, were found to be made exclusively by Leu-1
+
B cells. It is concluded that the Leu-1
+
lymphocytes represent a major subset of the normal human B cell repertoire and include the B cells capable of making autoantibodies similar to those found in systemic lupus erythematosus and rheumatoid arthritis.
Gene for von Recklinghausen Neurofibromatosis Is in the Pericentromeric Region of Chromosome 17
Authors: Barker D. , Wright E. , Nguyen K. , Cannon L. , Fain P. , Goldgar D. , Bishop D. T. , Carey J. , Baty B. , Kivlin J. , Willard H. , Waye J. S. , Greig G. , Leinwand L. , Nakamura Y. , O'Connell P. , Leppert M. , Lalouel J.-M. , White R. , Skolnick M.
Published: October 2006

Linkage analysis of 15 Utah kindreds demonstrated that a gene responsible for von Recklinghausen neurofibromatosis (NF) is located near the centromere on chromosome 17. The families also gave no evidence for heterogeneity, indicating that a significant proportion of NF cases are due to mutations at a single locus. Further genetic analysis can now refine this localization and may lead to the eventual identification and cloning of the defective gene responsible for this disorder.
Clathrin Requirement for Normal Growth of Yeast
Authors: Lemmon Sandra K. , Jones Elizabeth W.
Published: October 2006

Clathrin-coated membranes and coated vesicles take part in the selective transfer of proteins between different subcellular compartments of eukaryotic cells. To allow assessment of the role of clathrin in vesicular transport, genetic analysis of the clathrin heavy chain gene (
CHC1
) in
Saccharomyces cerevisiae
was initiated. The complete heavy chain gene was cloned, and the effects of deletion of this gene were studied. The null mutation (
chc1
-Δ) is lethal unless a suppressor of clathrin deficiency (
scd1
) is present. Even in the presence of the suppressor gene, mutants lacking the clathrin heavy chain grow slowly, are genetically unstable, are morphologically abnormal, and show loss of or reduction in several yeast functions. These results indicate that clathrin is required for normal growth of yeast, and, therefore, most likely, for growth of all eukaryotic cells.
Role of the Protein Moiety of Ribonuclease P, a Ribonucleoprotein Enzyme
Authors: Reich Claudia , Olsen Gary J. , Pace Bernadette , Pace Norman R.
Published: October 2006

The
Bacillus subtilis
ribonuclease P consists of a protein and an RNA. At high ionic strength the reaction is protein-independent; the RNA alone is capable of cleaving precursor transfer RNA, but the turnover is slow. Kinetic analyses show that high salt concentrations facilitate substrate binding in the absence of the protein, probably by decreasing the repulsion between the polyanionic enzyme and substrate RNAs, and also slow product release and enzyme turnover. It is proposed that the ribonuclease P protein, which is small and basic, provides a local pool of counter-ions that facilitates substrate binding without interfering with rapid product release.
Brain Stem Neurons in Modified Pathways for Motor Learning in the Primate Vestibulo-Ocular Reflex
Authors: Lisberger Stephen G. , Pavelko Terri A.
Published: October 2006

The vestibulo-ocular reflex (VOR) stabilizes retinal images by generating smooth eye movements that are equal in amplitude and opposite in direction to head turns. Whenever image motion occurs persistently during head turns, the VOR undergoes motor learning; as a result image stability is gradually restored. A group of brain stem neurons that are in the modified pathways has now been described. The neurons express changes in firing in association with motor learning in the VOR and receive monosynaptic inhibition from the flocculus of the cerebellum. The changes in firing have an appropriate magnitude and are expressed at the correct latency to account for the altered VOR. The response properties of the neurons point to their brain stem vestibular inputs for further investigation of the site of motor learning.
X-Ray Standing Waves: A Molecular Yardstick for Biological Membranes
Authors: Bedzyk M. J. , Bilderback D. H. , Bommarito G. M. , Caffrey M. , Schildkraut J. S.
Published: October 2006

Structural information on an atomic scale has been obtained for a Langmuir-Blodgett (LB) trilayer system by means of long-period x-ray standing waves. The LB trilayer of zinc and cadmium arachidate was deposited on a layered synthetic microstructure (LSM) consisting of 200 tungsten/silicon layer pairs with a 25 Å period. A 30 Å thermally induced inward collapse of the zinc atom layer that was initially located in the LB trilayer at 53 A above the LSM surface has been observed. The mean position and width of the zinc atom layer was determined with a precision of ± 0.3 Å.
Evolutionary Social Psychology and Family Homicide
Authors: Daly Martin , Wilson Margo
Published: October 2006

Homicide is an extreme manifestation of interpersonal conflict with minimal reporting bias and can thus be used as a conflict "assay." Evolutionary models of social motives predict that genetic relationship will be associated with mitigation of conflict, and various analyses of homicide data support this prediction. Most "family" homicides are spousal homicides, fueled by male sexual proprietariness. In the case of parent-offspring conflict, an evolutionary model predicts variations in the risk of violence as a function of the ages, sexes, and other characteristics of protagonists, and these predictions are upheld in tests with data on infanticides, parricides, and filicides.
Xeroderma Pigmentosum Group E Cells Lack a Nuclear Factor That Binds to Damaged DNA
Authors: Chu Gilbert , Chang Elaine
Published: October 2006

The disease xeroderma pigmentosum is characterized by deficient repair of damaged DNA. Fusions of cells from different patients have defined nine genetic complementation groups (A through I), implying that DNA repair in humans involves multiple gene products. In this report, an extension of the gel electrophoresis binding assay was used to identify at least one nuclear factor that (i) bound to DNA damaged by ultraviolet radiation or the antitumor drug cisplatin, but (ii) was notably absent in cells from complementation group E. Therefore, the factor appears to participate in a versatile DNA repair pathway at the stage of binding and recognition.
A Larger Spectrum of Severe HIV-1—Related Disease in Intravenous Drug Users in New York City
Authors: Stoneburner Rand L. , Des Jarlais Don C. , Benezra Diane , Gorelkin Leo , Sotheran Jo L. , Friedman Samuel R. , Schultz Stephen , Marmor Michael , Mildvan Donna , Maslansky Robert
Published: October 2006

Increasing mortality in intravenous (IV) drug users not reported to surveillance as acquired immunodeficiency syndrome (AIDS) has occurred in New York City coincident with the AIDS epidemic. From 1981 to 1986, narcotics-related deaths increased on average 32% per year from 492 in 1981 to 1996 in 1986. This increase included deaths from AIDS increasing from 0 to 905 and deaths from other causes, many of which were infectious diseases, increasing from 492 to 1091. Investigations of these deaths suggest a causal association with human immunodeficiency virus (HIV) infection. These deaths may represent a spectrum of HIV-related disease that has not been identified through AIDS surveillance and has resulted in a large underestimation of the impact of AIDS on IV drug users and blacks and Hispanics.
The Global Impact of the Chernobyl Reactor Accident
Authors: Anspaugh Lynn R. , Catlin Robert J. , Goldman Marvin
Published: October 2006

Radioactive material was deposited throughout the Northern Hemisphere as a result of the accident at the Chernobyl Nuclear Power Station on 26 April 1986. On the basis of a large amount of environmental data and new integrated dose assessment and risk models, the collective dose commitment to the ∼3 billion inhabitants is calculated to be 930,000 person-gray, with 97% in the western Soviet Union and Europe. The best estimates for the lifetime expectation of fatal radiogenic cancer would increase the risk from 0 to 0.02% in Europe and 0 to 0.003% in the Northern Hemisphere. By means of an integration of the environmental data, it is estimated that ∼100 petabecquerels of cesium-137 (1 PBq = 10
15
Bq) were released during and subsequent to the accident.
Recombinational Switch for Gene Expression
Authors: Zieg Janine , Silverman Michael , Hilmen Marcia , Simon Melvin
Published: October 2006

Flagellar antigens are specified by two genes, H1 and H2. The expression of these genes is regulated such that only one gene activity, or phase, is expressed at a given time. Molecular cloning techniques were used to isolate the segments of
Salmonella
DNA which contain these genetic loci. Heteroduplex analyses revealed an anomaly in the cloned fragment, that is, an apparent inversion, which was shown to be adjacent to the H2 gene. A correlation was demonstrated between the phase state of the H2 gene and the sequence of the adjacent segment. We propose that an inversion of this region is the phase-determining event in flagellar gene expression in
Salmonella
.