bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring the Accuracy of Diagnostic Systems
Authors: Swets John A.
Published: October 2006

Diagnostic systems of several kinds are used to distinguish between two classes of events, essentially "signals" and "noise." For them, analysis in terms of the "relative operating characteristic" of signal detection theory provides a precise and valid measure of diagnostic accuracy. It is the only measure available that is uninfluenced by decision biases and prior probabilities, and it places the performances of diverse systems on a common, easily interpreted scale. Representative values of this measure are reported here for systems in medical imaging, materials testing, weather forecasting, information retrieval, polygraph lie detection, and aptitude testing. Though the measure itself is sound, the values obtained from tests of diagnostic systems often require qualification because the test data on which they are based are of unsure quality. A common set of problems in testing is faced in all fields. How well these problems are handled, or can be handled in a given field, determines the degree of confidence that can be placed in a measured value of accuracy. Some fields fare much better than others.
Xenopus laevis
in Developmental and Molecular Biology
Authors: Dawid Igor B. , Sargent Thomas D.
Published: October 2006

Xenopus laevis
is a prime system for the study of embryogenesis in vertebrates. Both prelocalized information in the egg and inductive interactions between cells contribute to the ordered increase in complexity during development. Embryonic induction, discovered in amphibians, is being studied intensely in
Xenopus
; recent work suggests a role for growth factors in this process. Contributions of the
Xenopus
system to the analysis of ribosomal and 5
S
RNA genes, and the diverse and highly productive applications of the oocyte injection technology, are also summarized.
The Protein Kinase Family: Conserved Features and Deduced Phylogeny of the Catalytic Domains
Authors: Hanks Steven K. , Quinn Anne Marie , Hunter Tony
Published: October 2006

In recent years, members of the protein kinase family have been discovered at an accelerated pace. Most were first described, not through the traditional biochemical approach of protein purification and enzyme assay, but as putative protein kinase amino acid sequences deduced from the nucleotide sequences of molecularly cloned genes or complementary DNAs. Phylogenetic mapping of the conserved protein kinase catalytic domains can serve as a useful first step in the functional characterization of these newly identified family members.
Human Aging: Usual and Successful
Authors: Rowe John W. , Kahn Robert L.
Published: October 2006

Research in aging has emphasized average age-related losses and neglected the substantial heterogeneity of older persons. The effects of the aging process itself have been exaggerated, and the modifying effects of diet, exercise, personal habits, and psychosocial factors underestimated. Within the category of normal aging, a distinction can be made between usual aging, in which extrinsic factors heighten the effects of aging alone, and successful aging, in which extrinsic factors play a neutral or positive role. Research on the risks associated with usual aging and strategies to modify them should help elucidate how a transition from usual to successful aging can be facilitated.
Localization, Secretion, and Action of Inhibin in Human Placenta
Authors: Petraglia Felice , Sawchenko Paul , Lim Alan T. W. , Rivier Jean , Vale Wylie
Published: October 2006

Inhibin is a gonadal glycoprotein hormone that regulates the production of follicle-stimulating hormone (FSH) by the anterior pituitary gland and exhibits intragonadal actions as well. The present study shows that inhibin-like immunoreactivity (inhibin-LI) is present in cells of the cytotrophoblast layer of human placenta at term and in primary cultures of human trophoblasts. Human chorionic gonadotropin (hCG) stimulated secretion of inhibin-LI from these cultured placental cells. This effect was mimicked by 8-bromo-cyclic adenosine monophosphate (8-bromo-cAMP), forskolin, and cholera toxin, suggesting that the mechanism of hCG induction of placental inhibin-LI secretion is cAMP-dependent. Incubation with an antiserum that binds the α-subunit of human inhibin increased the secretion of hCG and gonadotropin-releasing hormone-like immunoreactivity (GnRH-LI) from trophoblast cells in culture, suggesting a local tonic inhibitory action of endogenous inhibin on hCG and GnRH-LI release. The action of inhibin on hCG secretion may partially require the presence of placental GnRH, as suggested by evidence that a synthetic GnRH antagonist partially reverses the hCG increase induced by inhibin immunoneutralization. Results suggest paracrine roles for both inhibin and GnRH in the regulation of placental hCG production.
Severely Impaired Adipsin Expression in Genetic and Acquired Obesity
Authors: Flier Jeffrey S. , Cook Kathleen Sue , Usher Patricia , Spiegelman Bruce M.
Published: October 2006

Adipsin, a serine protease homolog, is synthesized and secreted by adipose cells and is found in the bloodstream. The expression of adipsin messenger RNA (mRNA) and protein was analyzed in rodents during metabolic perturbations and in several experimental models of obesity. Adipsin mRNA abundance is increased in adipose tissue during fasting in normal rats and in diabetes due to streptozotocin-induced insulin deficiency. Adipsin mRNA abundance decreased during the continuous infusion of glucose, which induces a hyperglycemic, hyperinsulinemic state that is accompanied by an increased adipose mass; it is suppressed (> 100-fold) in two strains of genetically obese mice (
db
/
db
and
ob
/
ob
), compared to their congenic counterparts, and is also reduced when obesity is induced chemically by injection of monosodium glutamate into newborn mice. Circulating adipsin protein is decreased in these animal models of obesity, as determined by immunoblotting with antisera to adipsin. Little change in adipsin expression is observed in a model of obesity obtained by pure overfeeding of normal rats (cafeteria model). These data suggest a possible role for adipsin in the above-mentioned disordered metabolic states, and raise the possibility that adipsin expression may be used to distinguish obesities that arise from certain genetic or metabolic defects from those that result from pure overfeeding.
An in Vitro Neurite-Promoting Antigen Functions in Axonal Regeneration in Vivo
Authors: Sandrock Alfred W. , Matthew William D.
Published: October 2006

The function of the neurite growth-promoting antigen INO has been tested in an in vivo neurite regeneration system, the rat iris. The sympathetic innervation of the irides was removed by a single systemic injection of 6-hydroxydopamine. The subsequent regeneration of sympathetic axons into the iris of one eye bathed by the INO antibody, which inhibits neurite growth in vitro, was compared with the regrowth of sympathetic axons into the iris of the animal's other eye, which contained control antibody. Antibodies were released within the eye by implanted hybridoma cells. Neurite regeneration was measured by assaying [
3
H]norepinephrine uptake into freshly explanted irides. The blockage of the function of the INO antigen by the antibody resulted in a decreased rate of axonal regeneration, thus suggesting the involvement of the INO antigen in the process of neurite regeneration in vivo.
Suid Evolution and Correlation of African Hominid Localities
Authors: White T. D. , Harris J. M.
Published: October 2006

Recently discovered Plio-Pleistocene vertebrate assemblages have allowed complete systematic revision of the sub-Saharan African Suidae. New phylogenies are proposed for the 7 genera and 16 species of fossil and extant representatives. Suids are common elements of African Plio-Pleistocene faunas, and their evolutionary trends, particularly in the species
Mesochoerus limnetes
and
Metridiochoerus andrewsi
, are of great correlative value. Suid data are employed in a refinement of stratigraphic correlations at Omo Shungura, Olduvai, and east of Lake Turkana (formerly East Rudolf) and in a correlation of East African and South African sites, with important implications for interpretation of hominid evolution. The suid record also bears significantly on questions of theoretical evolutionary biology.
The T Cell Receptor
Authors: Marrack Philippa , Kappler John
Published: October 2006

The primary structure of T cell receptor proteins and genes is well understood. Immunologists are now trying to understand the properties of these interesting molecules. Evidence suggests that T cell αβ receptors recognize a complex of an antigen-derived peptide bound to one of the cell-surface products of the major histocompatibility complex (MHC) genes. It is likely that αβ receptors and MHC proteins have coevolved to have some affinity for each other. During T cell development in the thymus, cells bearing self-reactive receptors are deleted by the mechanisms of tolerance, and cells are preferentially allowed to mature if they bear receptors that will be able to recognize antigen plus self-MHC after they have become full-fledged T cells. Some explanations for these phenomena have been tested, but no satisfactory theory can yet be proposed to account for them.
Some Thoughts on Clinical Trials, Especially Problems of Multiplicity
Authors: Tukey John W.
Published: October 2006

Problems of statistical and conceptual design of experiments are exacerbated by ethical issues in many, if not most, clinical trials. Statutory requirements of demonstrated effectiveness are far from being clearly resolved—either qualitatively or quantitatively. Ethics, bolstered by informed consent, are likely to keep us from ever learning the answer to many questions. Unbalanced boundaries, focusing-down designs, historical controls, and not-very-sequential designs are among the possible consequences.
Epidemiology of HIV Infection and AIDS in the United States
Authors: Curran James W. , Jaffe Harold W. , Hardy Ann M. , Morgan W. Meade , Selik Richard M. , Dondero Timothy J.
Published: October 2006

By the end of 1987, nearly 50,000 cases of acquired immunodeficiency syndrome (AIDS) had been reported since 1981, 20,745 in the past year alone. Black and Hispanic adults and children have reported rates 3 to 12 times as high as whites. This can be largely attributed to higher reported rates in black and Hispanic intravenous (IV) drug abusers, their sex partners, and infants. In 1986, reported AIDS deaths increased adult male and female mortality in the United States by an estimated 0.7 and 0.07%, respectively, with much greater increases in selected age groups or areas of the country. The greatest variation in infection with the human immunodeficiency virus (HIV) (0 to 70%) has been found in surveys of IV drug abusers, while surveys of homosexual men reveal infection rates of 20 to 50%. Infection with HIV ranged from 0 to 2.6% in limited sexually transmitted disease clinic surveys of heterosexual men and women without a history of IV drug abuse or known sexual contact with persons at increased risk. The modes of HIV transmission are now well understood, but a large amount of biologic variability in efficiency of transmission remains to be explained. The period between initial infection with HIV and the development of AIDS is variable, but the risk for disease progression increases with duration of infection.
Biologically Effective Ultraviolet Radiation: Surface Measurements in the United States, 1974 to 1985
Authors: Scotto Joseph , Cotton Gerald , Urbach Frederick , Berger Daniel , Fears Thomas
Published: October 2006

Recent reports of stratospheric ozone depletion have prompted concerns about the levels of solar ultraviolet radiation that reach the earth's surface. Since 1974 a network of ground-level monitoring stations in the United States has tracked measurements of biologically effective ultraviolet radiation (UVB, 290 to 330 nanometers). The fact that no increases of UVB have been detected at ground levels from 1974 to 1985 suggests that meteorological, climatic, and environmental factors in the troposphere may play a greater role in attenuating UVB radiation than was previously suspected.
Three-Dimensional Structure of Cholera Toxin Penetrating a Lipid Membrane
Authors: Ribi Hans O. , Ludwig David S. , Mercer K. Lynne , Schoolnik Gary K. , Kornberg Roger D.
Published: October 2006

Two-dimensional crystals of cholera toxin bound to receptors in a lipid membrane give diffraction extending to 15 Å resolution. Three-dimensional structure determination reveals a ring of five B subunits on the membrane surface, with one-third of the A subunit occupying the center of the ring. The remaining mass of the A subunit appears to penetrate the hydrophobic interior of the membrane. Cleavage of a disulfide bond in the A subunit, which activates the toxin, causes a major conformational change, with the A subunit mostly exiting from the B ring.
Humanity in Science: A Perspective and a Plea
Authors: Goodfield June
Published: October 2006

The phrase "humanity in science" encompasses several problems of various dimensions, which have been present for a long period. Their particular force can be most clearly appreciated by seeing the historical circumstances in which they arose and by examining the changing nature of the social contract between the scientific profession and society. The new ethical imperatives presently operating within society call for new responses. In addition, new ways must be found of mirroring scientific activity so as to more faithfully reflect its real nature to and incorporate it into our culture.
Visualizing Gene Expression in Time and Space in the Filamentous Bacterium
Streptomyces coelicolor
Authors: Schauer Alan , Ranes Monica , Santamaria Ramon , Guijarro Jose , Lawlor Elizabeth , Mendez Carmen , Chater Keith , Losick Richard
Published: October 2006

Streptomycetes are prokaryotic microorganisms that exhibit a complex, mycelial fungus-like cycle of morphological differentiation. Development involves at least two spatially separated types of cells: the branching hyphae of the substrate mycelium, which penetrate the stratum upon which the colony feeds, and the upwardly protruding hyphae of the aerial mycelium, which undergo metamorphosis into spores. The luciferase-encoding
luxA
and
luxB
operon of the luminescent marine bacterium
Vibrio harveyi
was used as a promoter probe to visualize gene expression in differentiating colonies of
Streptomyces coelicolor
. Promoters for developmental genes of several kinds gave distinctive temporal and spatial patterns of light emission.
Metals as Regulators of Heme Metabolism
Authors: Maines Mahin D. , Kappas Attallah
Published: October 2006

Heme is essential for cell respiration, energy generation, and oxidative biotransformations. The latter function is exemplified by the oxidative metabolism of various endogenous and exogenous chemicals catalyzed by the heme protein cytochrome P-450. Recent studies have established that metal ions directly regulate cellular content of heme, and thus of heme proteins by controlling production of δ-aminolevulinate synthetase and heme oxygenase, the rate-limiting enzymes for heme synthesis and degradation, respectively. Metal ions also alter cellular content of glutathione. In excess amounts, metal ions greatly accelerate the turnover and degradation of heme and substantially impair the oxidative functions of cells—particularly those dependent on cytochrome P-450. As a result, the biological impact of chemicals which are detoxified or metabolically transformed by the P-450 system is greatly altered.
Behavioral Dissociation of Dishabituation, Sensitization, and Inhibition in
Aplysia
Authors: Marcus Emilie A. , Nolen Thomas G. , Rankin Catharine H. , Carew Thomas J.
Published: October 2006

Three forms of nonassociative learning (habituation, dishabituation, and sensitization) have commonly been explained by a dual-process view in which a single decrementing process produces habituation and a single facilitatory process produces both dishabituation and sensitization. A key prediction of this view is that dishabituation and sensitization should always occur together. However, we show that dishabituation and sensitization, as well as an additional process, inhibition, can be behaviorally dissociated in
Aplysia
by (i) their differential time of onset, (ii) their differential sensitivity to stimulus intensity, and (iii) their differential emergence during development. A simple dual-process view cannot explain these results; rather, a multiprocess view appears necessary to account for nonassociative learning in
Aplysia
.
Vasopressin mRNA in the Suprachiasmatic Nuclei: Daily Regulation of Polyadenylate Tail Length
Authors: Robinson Bruce G. , Frim David M. , Schwartz William J. , Majzoub Joseph A.
Published: October 2006

Daily variation has been found in the length of the polyadenylate tail attached to vasopressin messenger RNA in the suprachiasmatic nuclei, which is the location of an endogenous circadian pacemaker in mammals. No such variation was found in the supraoptic or paraventricular nuclei. This variation in the length of the polyadenylate tail may underlie the circadian rhythm of vasopressin peptide levels in cerebrospinal fluid and is a unique example of a daily rhythm in messenger RNA structure.
A Nonpeptide Morphine-Like Compound: Immunocytochemical Localization in the Mouse Brain
Authors: Gintzler Alan R. , Gershon Michael D. , Spector Sydney
Published: October 2006

A nonpeptide morphine-like compound (MLC) which cross reacts with morphine-specific antibodies has been localized with the use of immunocytochemistry. This morphine-like compound is found in neuronal perikarya or processes (or both) in nuclei related to vestibular, cerebellar, and raphe systems.
Fish Oils Inhibit Endothelial Cell Production of Platelet-Derived Growth Factor-Like Protein
Authors: Fox Paul L. , DiCorleto Paul E.
Published: October 2006

Diets rich in fish and fish oils are associated with a reduced risk of cardiovascular disease and atherosclerosis. The interaction of a commercial fish oil extract (MaxEPA) with vascular endothelial cells (ECs) was studied as a possible mechanism for this protective effect. MaxEPA almost completely inhibited EC production of platelet-derived growth factor-like protein (PDGFc) while other lipids had a lesser effect or no effect. Overall protein synthesis was not reduced, nor was the inhibition due to defective secretion or increased degradation of the growth factor. Antioxidants suppressed the inhibitory activity of MaxEPA indicating that free radical oxidative processes were required for the inhibition. These results suggest that fish oils may suppress intimal smooth muscle cell proliferation by decreasing the production of EC-derived paracrine growth factors. This inhibitory process represents a possible molecular mechanism for the antiatherosclerotic action of marine lipids.
Role of the Glutathione Redox Cycle in Acquired and de Novo Multidrug Resistance
Authors: Kramer Robert A. , Zakher Jehane , Kim George
Published: October 2006

Drug resistance represents a major obstacle to successful cancer chemotherapy. However, the specific biochemical mechanisms responsible for clinical drug resistance are unknown. In these studies resistance to the antitumor agent adriamycin was found to involve two mechanisms, one that decreased drug accumulation by the P170 mechanism and another that altered the glutathione redox cycle, an important pathway in the detoxification of reactive oxygen. This dual mechanism of drug resistance was demonstrated in cell lines that had acquired the multidrug-resistant phenotype and in human colorectal cancer cells with de novo resistance. These studies support a model of acquired and de novo multidrug resistance that includes alterations in both drug accumulation and the glutathione redox cycle.
Physical Analysis of Transcription Preinitiation Complex Assembly on a Class II Gene Promoter
Authors: Van Dyke Michael W. , Roeder Robert G. , Sawadogo Michèle
Published: October 2006

Transcription of protein-encoding genes by human RNA polymerase II requires multiple ancillary proteins (transcription factors). Interactions between these proteins and the promoter DNA of a viral class II gene (the major late transcription unit of adenovirus) were investigated by enzymatic and chemical footprinting. The experiments indicated that the assembly of functionally active RNA polymerase II-containing transcription preinitiation complexes requires a complete set of transcription factors, and that both specific protein-DNA and protein-protein interactions are involved. This allows individual steps along the transcription reaction pathway to be tested directly, thus providing a basis for understanding basic transcription initiation mechanisms as well as the regulatory processes that act on them.
Genetics and Demography in Biological Conservation
Authors: Lande Russell
Published: October 2006

Predicting the extinction of single populations or species requires ecological and evolutionary information. Primary demographic factors affecting population dynamics include social structure, life history variation caused by environmental fluctuation, dispersal in spatially heterogeneous environments, and local extinction and colonization. In small populations, inbreeding can greatly reduce the average individual fitness, and loss of genetic variability from random genetic drift can diminish future adaptability to a changing environment. Theory and empirical examples suggest that demography is usually of more immediate importance than population genetics in determining the minimum viable sizes of wild populations. The practical need in biological conservation for understanding the interaction of demographic and genetic factors in extinction may provide a focus for fundamental advances at the interface of ecology and evolution.
Dynamic Instability of Sheared Microtubules Observed by Quasi-Elastic Light Scattering
Authors: Keates Robert A. B. , Hallett F. Ross
Published: October 2006

The kinetics of microtubule reassembly was studied in vitro by quasi-elastic light scattering (QELS). When microtubules assembled in the absence of microtubule-associated proteins (MAPs) were sheared, they rapidly depolymerized, recovered, and reassembled. The mean length of the recovered microtubules was the same as that observed just before shearing, implying that on average one fragment per original microtubule survived the fragmentation and recovery. When microtubules that contained 25 percent brain MAP were sheared, the fragments did not depolymerize extensively and the average length of the fragments decreased by a factor of 3 relative to the unsheared sample. The results support the dynamic instability model, which predicts that cellular microtubules are latently unstable structures protected on their ends by stabilizing caps.
Fluorescence-Immunocytochemistry: Simultaneous Localization of Catecholamines and Gonadotropin-Releasing Hormone
Authors: McNeill Thomas H. , Sladek John R.
Published: October 2006

Gonadotropin-releasing hormone and dopamine were identified simultaneously in the same block of tissue from the median eminence of the rat brain. Two distinct bands of dopamine terminals were found in the lateral median eminence: an inner band which overlapped the gonadotropin-releasing hormone terminals and an outer band which appeared juxtaposed to portal capillaries.
Human Multidrug-Resistant Cell Lines: Increased
mdr
1 Expression Can Precede Gene Amplification
Authors: Shen D.-W. , Fojo A. , Chin J. E. , Roninson I. B. , Richert N. , Pastan I. , Gottesman M. M.
Published: October 2006

The development of simultaneous resistance to multiple structurally unrelated drugs is a major impediment to cancer chemotherapy. Multidrug resistance in human KB carcinoma cells selected in colchicine, vinblastine, or Adriamycin is associated with amplification of specific DNA sequences (the multidrug resistance locus,
mdr
1). During colchicine selection resistance is initially accompanied by elevated expression of a 4.5-kilobase
mdr
1 messenger RNA (mRNA) without amplification of the corresponding genomic sequences. During selection for increased levels of resistance, expression of this mRNA is increased simultaneously with amplification of
mdr
1 DNA. Increased expression and amplification of
mdr
1 sequences were also found in multidrug-resistant sublines of human leukemia and ovarian carcinoma cells. These results suggest that increased expression of
mdr
1 mRNA is a common mechanism for multidrug resistance in human cells. Activation of the
mdr
1 gene by mutations or epigenetic changes may precede its amplification during the development of resistance.
Relationship Between the c-
myb
Locus and the 6q- Chromosomal Aberration in Leukemias and Lymphomas
Authors: Barletta Cosimo , Pelicci Pier-Giuseppe , Kenyon Lawrence C. , Smith Stephen D. , Dalla-Favera Riccardo
Published: October 2006

Deletions of the long arm of chromosome 6 (6q-) are frequently found in hematopoietic neoplasms, including acute lymphoblastic leukemias, non-Hodgkin lymphomas and (less frequently) myeloid leukemias. The c-
myb
proto-oncogene has been mapped to region 6q21-24, which suggests that it could be involved in the 6q- aberrations. By means of in situ chromosomal hybridization on cells from six hematopoietic malignancies, it was demonstrated that the c-
myb
locus is not deleted, but is retained on band q22, which is consistently bordered by the chromosomal breakpoints in both interstitial and terminal 6q- deletions. The deletion breakpoints were located at some distance from the
myb
locus since no rearrangement of c-
myb
sequences was found. In one case, however, amplification of the entire c-
myb
locus was detectable. Furthermore, in all cases tested that carry 6q- deletions,
myb
messenger RNA levels were significantly higher than in normal cells or in malignant cells matched for lineage and stage of differentiation but lacking the 6q- marker. These results indicate that 6q- deletions are accompanied by structural and functional alterations of the c-
myb
locus and that these alterations may be involved in the pathogenesis of leukemias and lymphomas.
β-Adrenergic Regulation of Adenosine 3′,5′-Monophosphate Concentration in Brain Microvessels
Authors: Herbst Timothy J. , Raichle Marcus E. , Ferrendelli James A.
Published: October 2006

Norepinephrine increases the concentration of adenosine 3′,5′-monophosphate (cyclic AMP) in an incubated suspension of brain microvessels. This response can be matched by other drugs that stimulate the β receptors, but the α-adrenergic agonist phenylephrine is without effect; β-adrenergic blockade abolishes the response while α-adrenergic blockade produces no change. The data support the contention that cerebral capillary function is subject to adrenergic neural control.
Two Different
cis
-Active Elements Transfer the Transcriptional Effects of Both EGF and Phorbol Esters
Authors: Elsholtz Harry P. , Mangalam Harry J. , Potter Ellen , Albert Vivian R. , Supowit Scott , Evans Ronald M. , Rosenfeld Michael G.
Published: October 2006

Short
cis
-active sequences of the rat prolactin or Moloney murine leukemia virus genes transfer transcriptional regulation by both epidermal growth factor and phorbol esters to fusion genes. These sequences act in a position- and orientation-independent manner. Competitive binding analyses with nuclear extracts from stimulated and unstimulated cells suggest that different
trans
-acting factors associate with the regulatory sequence of each gene. A model is proposed suggesting that both epidermal growth factor and phorbol esters stimulate the transcription of responsive genes via discrete classes of hormone-dependent, enhancer-like elements that bind different
trans
-acting factors, even in the absence of hormone stimulation.
The Dynamics of Free Calcium in Dendritic Spines in Response to Repetitive Synaptic Input
Authors: Gamble Edward , Koch Christof
Published: October 2006

Increased levels of intracellular calcium at either pre- or postsynaptic sites are thought to precede changes in synaptic strength. Thus, to induce long-term potentiation in the hippocampus, periods of intense synaptic stimulation would have to transiently raise the levels of cytosolic calcium at postsynaptic sites—dendritic spines in the majority of cases. Since direct experimental verification of this hypothesis is not possible at present, calcium levels have been studied by numerically solving the appropriate electro-diffusion equations for two different postsynaptic structures. Under the assumption that voltage-dependent calcium channels are present on dendritic spines, free intracellular calcium in spines can reach micromolar levels after as few as seven spikes in 20 milliseconds. Moreover, a short, but high-frequency, burst of presynaptic activity is more effective in raising levels of calcium and especially of the calcium-calmodulin complex than sustained low-frequency activity. This behavior is different from that seen at the soma of a typical vertebrate neuron.
Identification of Putative Human T Cell Receptor δ Complementary DNA Clones
Authors: Hata Shingo , Brenner Michael B. , Krangel Michael S>
Published: October 2006

A novel T cell receptor (TCR) subunit termed TCR δ, associated with TCR γ and CD3 polypeptides, was recently found on a subpopulation of human T lymphocytes. T cell-specific complementary DNA clones present in a human TCR γδ T cell complementary DNA library were obtained and characterized in order to identify candidate clones encoding TCR δ. One cross-hybridizing group of clones detected transcripts that are expressed in lymphocytes bearing TCR γδ but not in other T lymphocytes and are encoded by genes that are rearranged in TCR γδ lymphocytes but deleted in other T lymphocytes. Their sequences indicate homology to the variable, joining, and constant elements of other TCR and immunoglobulin genes. These characteristics, as well as the immunochemical data presented in a companion paper, are strong evidence that the complementary DNA clones encode TCR δ.
Effect of Antibodies to Recombinant and Synthetic Peptides on
P. falciparum
Sporozoites in Vitro
Authors: Mazier D. , Mellouk S. , Beaudoin R. L. , Texier B. , Druilhe P. , Hockmeyer W. , Trosper J. , Paul C. , Charoenvit Y. , Young J. , Miltgen F. , Chedid L. , Chigot J. P. , Galley B. , Brandicourt O. , Gentilini M.
Published: October 2006

Antibodies were raised in mice immunized with several recombinant and synthetic peptides of the circumsporozoite protein of
Plasmodium falciparum
. The antibodies were evaluated for protective activity in a human hepatocyte culture system. They exerted their protective effect against the parasite at three points: sporozoite attachment to the hepatocyte surface, entry, and subsequent intracellular development. Inhibition of attachment and entry were found to be related to the antibody titer against the authentic circumsporozoite protein on the sporozoite surface, especially when peptides were administered with alum or complete Freund's adjuvant. Even when invasion was not totally inhibited, the presence of abnormal trophozoites and a frequent inhibition of schizont development in long-term cultures suggested continued activity of antibodies at the intracellular level after sporozoite penetration had been completed.
Effects of Naloxone on Schizophrenia: Reduction in Hallucinations in a Subpopulation of Subjects
Authors: Watson Stanley J. , Berger Philip A. , Akil Huda , Mills Mark J. , Barchas Jack D.
Published: October 2006

Endogenous opiate-like peptides (endorphins) are putative neuroregulators located throughout the mammalian brainstem. There is some evidence for their role in pain, stress, and affect. We report that the opiate antagonist, naloxone, alters some schizophrenic symptoms. In a double-blind, cross-over study, naloxone produced decreases in auditory hallucinations in some schizophrenic patients. This finding supports the hypothesis that the endorphins may play a roll in modulating hallucinations in a highly selected subgroup of chronically hallucinating schizophrenic patients.
A Genetic Approach to Analyzing Membrane Protein Topology
Authors: Manoil Colin , Beckwith Jon
Published: October 2006

Fusions of the secreted protein alkaline phosphatase to an integral cytoplasmic membrane protein of
Escherichia coli
showed different activities depending on where in the membrane protein the alkaline phosphatase was fused. Fusions to positions in or near the periplasmic domain led to high alkaline phosphatase activity, whereas those to positions in the cytoplasmic domain gave low activity. Analysis of alkaline phosphatase fusions to membrane proteins of unknown structure may thus be generally useful in determining their membrane topologies.
Purification and Biochemical Characterization of the Promoter-Specific Transcription Factor, Sp1
Authors: Briggs Michael R. , Kadonaga James T. , Bell Stephen P. , Tjian Robert
Published: October 2006

The biochemical analysis of cellular trans-activators involved in promoter recognition provides an important step toward understanding the mechanisms of gene expression in animal cells. The promoter selective transcription factor, Sp1, has been purified from human cells to more than 95 percent homogeneity by sequence-specific DNA affinity chromatography. Isolation and renaturation of proteins purified from sodium dodecyl sulfate polyacrylamide gels allowed the identification of two polypeptides (105 and 95 kilodaltons) as those responsible for recognizing and interacting specifically with the GC-box promoter elements characteristic of Sp1 binding sites.
Identification of Specific Transducin α Subunits in Retinal Rod and Cone Photoreceptors
Authors: Lerea Connie L. , Somers David E. , Hurley James B. , Klock Ingrid B. , Bunt-Milam Ann H.
Published: October 2006

Transducin is a guanyl nucleotide-binding protein that couples rhodopsin photolysis to hydrolysis of guanosine 3′,5′-monophosphate in rod photoreceptor cells of vertebrate retinas. Several complementary DNA clones encoding transducin subunits have recently been characterized. One clone, isolated from a bovine retina complementary DNA library, encodes a previously unidentified polypeptide with an amino acid sequence 78% identical to the sequence of the α subunit of bovine rod outer segment transducin. Antibodies to a synthetic peptide with amino acid sequence derived specifically from this novel polypeptide recognize a 41-kilodalton polypeptide in homogenates of bovine retina. Localization of this polypeptide in bovine retina by indirect immunofluorescence demonstrates that it is expressed only in cone outer segments. Antibodies to specific sequences found only in the rod transducin α subunit recognize a polypeptide localized only in the rod outer segment. Therefore, bovine rod and cone cells each express structurally related yet significantly different forms of transducin.
Optical Trapping and Manipulation of Viruses and Bacteria
Authors: Ashkin A. , Dziedzic J. M.
Published: October 2006

Optical trapping and manipulation of viruses and bacteria by laser radiation pressure were demonstrated with single-beam gradient traps. Individual tobacco mosaic viruses and dense oriented arrays of viruses were trapped in aqueous solution with no apparent damage using ∼120 milliwatts of argon laser power. Trapping and manipulation of single live motile bacteria and
Escherichia coli
bacteria were also demonstrated in a high-resolution microscope at powers of a few milliwatts.
Synthetic Maps of Human Gene Frequencies in Europeans
Authors: Menozzi P. , Piazza A. , Cavalli-Sforza L.
Published: October 2006

Multivariate techniques can be used to condense the information for a large number of loci and alleles into one or a few synthetic variables. The geographic distribution of synthetic variables can be plotted by the same technique used in mapping the gene frequency of a single allele. Synthetic maps were constructed for Europe and the Near East, with the use of principal components to condense the information of 38 independent alleles from ten loci. The first principal component summarizes close to 30 percent of the total information and shows gradients. Maps thus constructed show clines in remarkable agreement with those expected on the basis of the spread of early farming in Europe, thus supporting the hypothesis that this spread was a demic spread rather than a cultural diffusion of farming technology.
Age Determination of an Alaskan Mummy: Morphological and Biochemical Correlation
Authors: Masters Patricia M. , Zimmerman Michael R.
Published: October 2006

Aspartic acid racemization analysis of a tooth from an Alaskan mummy yielded an age at death of 53 (± 5) years, which correlates well with earlier estimates based on morphological features. This study illustrates the value of integrative approaches to paleopathologic problems and the importance of preserving rare specimens for the application of new techniques.
Clathrin Light Chains LCA and LCB Are Similar, Polymorphic, and Share Repeated Heptad Motifs
Authors: Kirchhausen T. , Scarmato P. , Harrison S. C. , Monroe J. J. , Chow E. P. , Mattaliano R. J. , Ramachandran K. L. , Smart J. E. , Ahn A. H. , Brosius J.
Published: October 2006

The clathrin light chains fall into two major classes, LCA and LCB. In an intact clathrin triskelion, one light chain, of either class, is bound to the proximal segment of a heavy chain leg. Analysis of rat brain and liver complementary DNA clones for LCA and LCB shows that the two light chain classes are closely related. There appear to be several members of each class having deletions of varying length aligned at the same position. A set of ten heptad elements, characteristic of α-helical coiled coils, is a striking feature of the central part of each derived amino acid sequence. These observations suggest a model in which the α-helical segment mediates binding to clathrin heavy chains and the amino- and carboxyl-terminal segments mediate interactions with other proteins. They also suggest an explanation for the observed tissue-dependent size variation for members of each class.
Prolonged Inhibition of Neurons by Neuroendocrine Cells in
Aplysia
Authors: Brownell Philip , Mayeri Earl
Published: October 2006

In the abdominal ganglion of
Aplysia
, a burst of action potentials in peptide-secreting neuroendocrine cells, the bag cells, produces slow inhibition of two identified bursting pacemaker neurons. The inhibition is due to a slow hyperpolarizing potential that reduces bursting pacemaker activity for 3 hours or more. The slow inhibitory potential results from a large and prolonged increase in membrane conductance to potassium ions as well as a slower ionic process that is relatively independent of membrane conductance.
Three-Dimensional Representation and Analysis of Brain Energy Metabolism
Authors: Hibbard Lyndon S. , McGlone James S. , Davis Donald W. , Hawkins Richard A.
Published: October 2006

Quantitative autoradiography of brain glucose metabolism has been combined with digital image processing to represent the brain as a three-dimensional (3-D) reconstruction of brain energy use. Autoradiographs contain enormous amounts of potentially useful data, but conventional analyses, based on tedious manual methods, can sample and analyze only a small portion of this information. Computer 3-D reconstruction provides a mechanism for observing and analyzing all the data; therefore, a system of computer programs was developed for this purpose. The programs use digital imaging methods for image registration, superimpose whole brain data sets, and allow resampling of the 3-D data in arbitrary planes for pixel-by-pixel comparisons among multiple 3-D sets. These programs operate on the mathematical properties of the images alone, obviating the need for manual image alignment. Various statistical analyses can be applied to the data directly to study the patterns of metabolic changes in different experiments. The system is applied to data from experiments on the influence of injectable anesthetics on cerebral glucose metabolism.
Local Retinal Regions Control Local Eye Growth and Myopia
Authors: Wallman Josh , Gottlieb Michael D. , Rajaram Vidya , Fugate-Wentzek Lisa A.
Published: October 2006

In chicks, visual deprivation leads to myopia and enlargement of the vitreous chamber of the eye. When chicks were raised with white translucent occluders over their eyes so that either the nasal half, the temporal half, or all of the retina was visually deprived, the resulting myopia (median = -15 diopters) was limited to the deprived part of the retina, regardless of which half of the retina was visually deprived; the nondeprived part remained nearly emmetropic. Correspondingly, the vitreous chamber was elongated only in the region of the visual deprivation, resulting in eyes with different asymmetric shapes depending on which retinal region was deprived. These results argue for a local regulation of ocular growth that is dependent on vision and suggest a hypothesis to explain the epidemiological association of myopia in humans with large amounts of reading. Because most nonfoveal retinal neurons have large receptive fields, they cannot resolve the individual letters on the printed page; this may lead to their activity being less during reading than during most other forms of visual stimulation. Thus, the impoverished stimulus situation of reading may lead to myopia, as do other types of visual form deprivation.
Physiological Evidence for Serial Processing in Somatosensory Cortex
Authors: Pons T. P. , Garraghty P. E. , Friedman D. P. , Mishkin M.
Published: October 2006

Removal of the representation of a specific body part in the postcentral cortex of the macaque resulted in the somatic deactivation of the corresponding body part in the second somatosensory area. In contrast, removal of the entire second somatosensory area had no grossly detectable effect on the somatic responsivity of neurons in the postcentral cortex. This direct electrophysiological evidence for serial cortical processing in somesthesia is similar to that found earlier for vision and, taken together with recent anatomical evidence, suggests that there is a common cortical plan for the processing of sensory information in the various sensory modalities.
Astrocytes Block Axonal Regeneration in Mammals by Activating the Physiological Stop Pathway
Authors: Liuzzi Francis J. , Lasek Raymond J.
Published: October 2006

Regenerating sensory axons in the dorsal roots of adult mammals are stopped at the junction between the root and spinal cord by reactive astrocytes. Do these cells stop axonal elongation by activating the physiological mechanisms that normally operate to stop axons during development, or do they physically obstruct the elongating axons? In order to distinguish these possibilities, the cytology of the axon tips of regenerating axons that were stopped by astrocytes was compared with the axon tips that were physically obstructed at a cul-de-sac produced by ligating a peripheral nerve. The terminals of the physically obstructed axon tips were distended with neurofilaments and other axonally transported structures that had accumulated when the axons stopped elongating. By contrast, neurofilaments did not accumulate in the tips of regenerating axons that were stopped by spinal cord astrocytes at the dorsal root transitional zone. These axo-glial terminals resembled the terminals that axons make on target neurons during normal development. On the basis of these observations, astrocytes appear to stop axons from regenerating in the mammalian spinal cord by activating the physiological stop pathway that is built into the axon and that normally operates when axons form stable terminals on target cells.
A Novel Mode of Arbovirus Transmission Involving a Nonviremic Host
Authors: Jones Linda D. , Davies Clive R. , Steele Gordon M. , Nuttall Patricia A.
Published: October 2006

In nature, infected and uninfected arthropod vectors often feed together on an animal. In mimicking this scenario in the laboratory, uninfected vectors were found to acquire virus while cofeeding on the same host as infected vectors. However, the vertebrate host on which they fed did not develop detectable levels of virus in its blood. These observations were made with Thogoto virus, an influenza-like virus of medical and veterinary significance.
Rhipicephalus appendiculatus
ticks were used as the vector and guinea pigs as the vertebrate host. The results demonstrate that a vertebrate that is apparently refractory to infection by an arthropod-borne virus can still play an important role in the epidemiology of the virus, and they suggest a novel mode of arthropod-borne virus transmission.
The Cognitive Unconscious
Authors: Kihlstrom John F.
Published: October 2006

Contemporary research in cognitive psychology reveals the impact of nonconscious mental structures and processes on the individual's conscious experience, thought, and action. Research on perceptual-cognitive and motoric skills indicates that they are automatized through experience, and thus rendered unconscious. In addition, research on subliminal perception, implicit memory, and hypnosis indicates that events can affect mental functions even though they cannot be consciously perceived or remembered. These findings suggest a tripartite division of the cognitive unconscious into truly unconscious mental processes operating on knowledge structures that may themselves be preconscious or subconscious.
Expression of an Exogenous Growth Hormone Gene by Transplantable Human Epidermal Cells
Authors: Morgan Jeffrey R. , Barrandon Yann , Green Howard , Mulligan Richard C.
Published: October 2006

Retrovirus-mediated gene transfer was used to introduce a recombinant human growth hormone gene into cultured human keratinocytes. The transduced keratinocytes secreted biologically active growth hormone into the culture medium. When grafted as an epithelial sheet onto athymic mice, these cultured keratinocytes reconstituted an epidermis that was similar in appearance to that resulting from normal cells, but from which human growth hormone could be extracted. Transduced epidermal cells may prove to be a general vehicle for the delivery of gene products by means of grafting.
Affinity Chromatography of Splicing Complexes: U2, U5, and U4 + U6 Small Nuclear Ribonucleoprotein Particles in the Spliceosome
Authors: Grabowski Paula J. , Sharp Phillip A.
Published: October 2006

The splicing process, which removes intervening sequences from messenger RNA (mRNA) precursors is essential to gene expression in eukaryotic cells. This site-specific process requires precise sequence recognition at the boundaries of an intervening sequence, but the mechanism of this recognition is not understood. The splicing of mRNA precursors occurs in a multicomponent complex termed the spliceosome. Such an assembly of components is likely to play a key role in specifying those sequences to be spliced. In order to analyze spliceosome structure, a stringent approach was developed to obtain splicing complexes free of cellular contaminants. This approach is a form of affinity chromatography based on the high specificity of the biotin-streptavidin interaction. A minimum of three subunits: U2, U5, and U4 + U6 small nuclear ribonucleoprotein particles were identified in the 35
S
spliceosome structure, which also contains the bipartite RNA intermediate of splicing. A 25
S
presplicing complex contained only the U2 particle. The multiple subunit structure of the spliceosome has implications for the regulation of a splicing event and for its possible catalysis by ribozyme or ribozymes.