bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonolfactory Sensory Pathway to the Telencephalon in a Teleost Fish
Authors: Finger Thomas E.
Published: October 2006

Pathways conveying lateral-line sensory information within the brain of a bullhead catfish terminate in a localized zone within the telencephalon. Thus, the telencephalon in teleosts, as in amniote species, contains regions that receive specific sensory input. Therefore, this lemniscal organization is not restricted to mammalian or amniote species but is a feature common to most, if not all, vertebrates.
Associative Learning in
Aplysia
: Evidence for Conditioned Fear in an Invertebrate
Authors: Walters Edgar T. , Carew Thomas J. , Kandel Eric R.
Published: October 2006

Aversive classical conditioning of
Aplysia californica
, a gastropod mollusk suited for neurobiological study, produces a learned reaction to the chemosensory conditioned stimulus that is expressed as a marked facilitation of four defensive responses: two graded reflexes (head and siphon withdrawal), an all-or-none fixed act (inking), and a complex fixed action pattern (escape locomotion). In addition, the conditioned stimulus produces a concomitant depression of at least one appetitive response, feeding. These extensive and selective actions of the conditioned stimulus in
Aplysia
resemble the actions of conditioned fear stimuli in higher mammals and suggest that the functional equivalent of fear occurs in invertebrates and thus may be an adaptive mechanism that is widespread in the animal kingdom.
Cure of Mice Infected with
Trypanosoma rhodesiense
by
cis
-Diamminedichloroplatinum (ii) and Disulfiram Rescue
Authors: Wysor Michael S. , Zwelling Leonard A. , Sanders James E. , Grenan Marie M.
Published: October 2006

Mice infected with Trypanosoma rhodesiense were treated concurrently with cis-diamminedichloroplatinum (II) (DDP), disulfiram, and hydration. Most of the mice (92.5 percent) were cured; inoculation of blood or suspensions of brain or heart from these animals did not produce disease in recipient mice. The dose of DDP needed to eliminate the trypanosomes, 3 milligrams per kilogram of body weight per day for 7 days, was lethally toxic unless the animals received disulfiram orally and subcutaneous injections of physiologic saline, which reduced the acute renal necrosis caused by DDP alone. Some mild to moderate reversible renal damage was noted upon pathologic examination of the treated mice.
Language-Related Potentials Specific to Human Language Cortex
Authors: Fried Itzhak , Ojemann George A. , Fetz Eberhard E.
Published: October 2006

Event-related potentials following silently named object pictures were recorded directly from the exposed left hemisphere of the human cortex at sites whose relation to naming was subsequently established by electrical stimulation mapping. Two simultaneous potential changes are specific to sites where stimulation disrupts naming: slow potentials at premotor sites and focal desynchronization at posterior sites surrounding the Sylvian fissure. These anatomically specific changes are also specific to the task—present with silent naming and absent in a spatial task with the same visual input. Overt speech is also preceded by slow potentials with earliest onset at premotor sites.
Indirect Costs of Federally Supported Research
Authors: Brown Kenneth T.
Published: October 2006

Indirect costs of federally supported research have increased steadily and dramatically since the current indirect cost policy became effective in 1966. The amount of research supported by any given level of federal funding has thus been markedly reduced, and this has become a critical factor limiting research support in the United States. The current policy has had multiple adverse effects that threaten the health of both the federal research program and the universities in which most of the research is conducted. This article examines the background and nature of the current policy, describes its consequences, and proposes simplifying modifications.
A Metronidazole Metabolite in Human Urine and Its Risk
Authors: Kock Ronald L. , Beaulieu Bernard B. , Chrystal Ewan J. T. , Goldman Peter
Published: October 2006

Metronidazole is a drug used for the treatment of trichomonal vaginitis, amebiasis, giardiasis, and certain anaerobic bacterial infections in humans. Acetamide and
N
-(2-hydroxyethyl)oxamic acid are metabolites of metronidazole in the rat, and we find small amounts of both metabolites in the urine of human patients taking the drug. Although acetamide is carcinogenic for rats, we do not believe that our finding further defines metronidazole's risk for humans. That risk can only be estimated from surveillance of people previously exposed to the drug.
The Mutation Component of Genetic Damage
Authors: Crow James F. , Denniston Carter
Published: October 2006

The mutation component,
M
, is a measure of the proportion of the impact of a genetic condition that is attributable to recurrent mutation. For a trait maintained by balance between mutation and directional selection,
M
is approximately the broad-sense heritability; for a measured character where the mean and optimum coincide,
M
is about half the heritability. If the narrow-sense heritability is high, the impact changes relatively rapidly with a change in mutation rate. If the narrow-sense heritability is low,
M
cannot be predicted, but the change in impact following a change in mutation rate, if any, is very slow.
Transbilayer Phospholipid Asymmetry in
Plasmodium knowlesi
-Infected Host Cell Membrane
Authors: Gupta C. M. , Mishra G. C.
Published: October 2006

The membranes from normal and
Plasmodium knowlesi
-infected rhesus monkey erythrocytes (90 to 95 percent infected with early ring stage) were analyzed for transbilayer distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS), by means of chemical and enzymatic probes. The external monolayer of the normal red cell membrane contained at least 68 to 72 percent of the total phosphatidylcholine and 15 to 20 percent of the total phosphatidylethanolamine. In the infected cell, the transmembrane phosphatidylcholine distribution appeared to be reversed, with only 20 to 30 percent of it being externally localized, whereas roughly equal amounts of phosphatidylethanolamine were present in the outer and inner surfaces. However, total phosphatidylserine in both the infected and normal red cells was exclusively internal. Unlike that in the normal intact cell, external phosphatidylethanolamine in the parasitized cell was readily accessible to phospholipase A
2
. These results indicate that significant changes in molecular architecture of the host cell membrane are the result of parasitization.
Estradiol and Progesterone Profiles Indicate a Lack of Endocrine Recognition of Pregnancy in the Opossum
Authors: Harder John D. , Fleming Michael W.
Published: October 2006

Concentrations of estradiol and progesterone in blood collected during the 12.5-day gestation period of the Virginia opossum were not significantly different from those during equivalent days of the estrous cycle. Progesterone was correlated with an index of corpora luteal mass. Ratios of estradiol to progesterone were highest 3 to 4 days before estrus and on the day of parturition.
Response Artifact in the Measurement of Neuroleptic-Induced Anhedonia
Authors: Ettenberg Aaron , Koob George F. , Bloom Floyd E.
Published: October 2006

Systemic administration of the neuroleptic drug α-flupenthixol attenuated lever-pressing behavior in rats responding for rewarding brain stimulation. The magnitude of this attenuation was dose-dependent and resembled the effects of reward reduction and termination. However, when the operant response requirements of the same rats were changed to nose poking, identical drug treatments produced relatively little attenuation in performance. These data do not support the belief that neuroleptics produce a general state of anhedonia. Rather, the apparent suppression of reinforced behaviors depends at least in part on the kinetic requirements of the response.
Brain Tumors in Children and Occupational Exposure of Parents
Authors: Peters John M. , Preston-Martin Susan , Yu Mimi C.
Published: October 2006

Ninety-two cases of brain tumor in children less than 10 years old were compared with 92 matched controls for parental occupational history. Cases were more likely than controls to show maternal occupations involving chemical exposure, paternal occupations involving solvents, and employment of father in the aircraft industry. These three factors were not affected by adjustment for the potential confounding variables examined in this study.
Brain 5β-Reductase: a Correlate of Behavioral Sensitivity to Androgen
Authors: Hutchison J. B. , Steimer T.
Published: October 2006

Testosterone is converted in the dove (
Streptopelia risoria
) brain to 5 β-reduced metabolites that do not affect behavior. In long-term castrated birds, which are relatively insensitive to the behavioral effects of testosterone, the activity of preoptic 5 β-reductase is increased. The increase, which is specific to the preoptic area, is reversed by estrogen. Inactivation of testosterone by 5 β-reduction may be involved in the control of brain sensitivity to androgen.
Selection by Consequences
Authors: Skinner B. F.
Published: October 2006

Selection by consequences is a causal mode found only in living things, or in machines made by living things. It was first recognized in natural selection, but it also accounts for the shaping and maintenance of the behavior of the individual and the evolution of cultures. In all three of these fields, it replaces explanations based on the causal modes of classical mechanics. The replacement is strongly resisted. Natural selection has now made its case, but similar delays in recognizing the role of selection in the other fields could deprive us of valuable help in solving the problems which confront us.
Copper Deficiency Suppresses the Immune Response of Mice
Authors: Prohaska Joseph R. , Lukasewycz Omelan A.
Published: October 2006

Mice fed a purified diet low in copper display anemia, hypoceruloplasminemia, depressed concentrations of liver copper, and elevated concentrations of liver iron. An impaired humoral-mediated immune response (decreased numbers of antibody-producing cells) is observed in mice with severe as well as marginal copper deficiency. The magnitude of this impairment is highly correlated with the degree of functional copper deficiency (hypoceruloplasminemia).
Novel Single-Pass Exchange of Circulating Uridine in Rat Liver
Authors: Gasser Thomas , Moyer James D. , Handschumacher Robert E.
Published: October 2006

Evidence is presented that the liver effects an essentially complete degradation of plasma uridine in a single pass and replaces it largely from hepatic pools of acid-soluble uridine nucleotides. The concentration of uridine in the hepatic vein of the rat was essentially the same as that in the arterial circulation and portal vein. However, the isolated perfused rat liver degraded more than 90 percent of infused [5-
3
H]uridine in a single passage. Similar results were found in vivo when tracer amounts of [
3
H]uridine and [
14
C]uridine were infused into the portal vein of an intact rat. Furthermore, less than 2 percent of the infused uridine entered the acid-soluble nucleotide pools of the liver after 30 minutes of infusion. Intraperitoneal injection of [
3
H]orotate allowed selective labeling of liver (and kidney) pyrimidines. After 3 hours, the specific activity of uridine in the hepatic vein was more than three times that in the arterial circulation. This unusual exchange, which is not saturated even at uridine concentrations as high as 50 μ
M
, contributes to the rapid turnover of plasma uridine and explains its inefficient utilization in peripheral tissues.
Natural Toxicants in Human Foods: Psoralens in Raw and Cooked Parsnip Root
Authors: Ivie G. Wayne , Holt Douglas L. , Ivey Marcellus C.
Published: October 2006

Parsnip root contains three photoactive, mutagenic, and photocarcinogenic psoralens in a total concentration of about 40 parts per million. These chemicals are not destroyed by normal cooking procedures (boiling or microwave); thus humans are exposed to appreciable levels of psoralens through the consumption of parsnip and possibly other psoralen-containing foodstuffs. The toxicologic consequences to man of such exposure may be speculated on the basis of medicinal and laboratory studies, but epidemiologic data are not available.
Hyperthermia-Induced Seizures in the Rat Pup: A Model for Febrile Convulsions in Children
Authors: Holtzman David , Obana Kathryn , Olson James
Published: October 2006

Seizures were produced in rat pups by ambient hyperthermia. Seizure threshold temperatures, measured rectally and intracerebrally, increased between 2 and 10 days of age. Electrocortical paroxysmal discharges were confirmed in hyperthermic 6- and 10-day-old pups. The increasing resistance to hyperthermic seizures with maturation and the electroencephalographic changes induced by hyperthermia are similar to those in young children.
Abdominal Vagotomy Blocks the Satiety Effect of Cholecystokinin in the Rat
Authors: Smith G. P. , Jerome C. , Cushin B. J. , Eterno R. , Simansky K. J.
Published: October 2006

The site where peripherally administered cholecystokinin-8 elicits satiety was investigated by injecting rats with cholecystokinin-8 (1 to 8 micrograms per kilogram of body weight, intraperitoneally) after they had received bilateral lesions of the ventromedial hypothalamus or after they had undergone bilateral abdominal vagotomy or selective vagotomies. Abdominal vagotomy or gastric vagotomy abolished or reduced the satiety effect of cholecystokinin, but lesions of the ventromedial hypothalamus did not. These results demonstrate that peripherally administered cholecystokinin acts in the abdomen through gastric vagal fibers and not directly on the brain to produce satiety in the rat.
Functional Restoration of Vision in the Cat After Long-Term Monocular Deprivation
Authors: Smith Douglas C.
Published: October 2006

Recovery of visual acuity was studied in six long-term monocularly deprived cats after removal of the nondeprived eye or reverse lid suture. Although both manipulations improved visual acuity, removal of the nondeprived eye was associated with more rapid recovery and higher final acuity than in reverse suture. These results are in agreement with the known electrophysiological effects of these recovery conditions and are also similar to the effects of reverse occlusion or loss of the nonamblyopic eye in human amblyopes.
Genetic Effects of the Atomic Bombs: A Reappraisal
Authors: Schull William J. , Otake Masanori , Neel James V.
Published: October 2006

Data are presented on four indicators of genetic effects from studies of children born to survivors of the atomic bombings of Hiroshima and Nagasaki. The indicators are frequency of untoward pregnancy outcomes (stillbirth, major congenital defect, death during first postnatal week); occurrence of death in live-born children, through an average life expectancy of 17 years; frequency of children with sex chromosome aneuploidy; and frequency of children with mutation resulting in an electrophoretic variant. In no instance is there a statistically significant effect of parental exposure; but for all indicators the observed effect is in the direction suggested by the hypothesis that genetic damage resulted from the exposure. On the basis of assumptions concerning the contribution that spontaneous mutation in the preceding generation makes to the indicators in question, it is possible to estimate the genetic doubling dose for radiation for the first three indicators (the data base is still too small for the fourth). The average of these estimates is 156 rems. This is some four times higher than the results from experimental studies on the mouse with comparable radiation sources, which have been the principal guide to the presumed human sensitivities. The relevance of these data in setting permissible limits for human exposures is discussed briefly.
Fluorescence of Photoreceptor Cells Observed in Vivo
Authors: Franceschini N. , Kirschfeld K. , Minke B.
Published: October 2006

Most rhabdomeres in the eye of the fly (
Musca domestica
) are fluorescent. One kind of fluorescent emission emanates from a photoproduct of the visual pigment, other kinds may be ascribed to photostable pigments. These phenomena provide not only a means of spectrally mapping the retina but also a new spectroscopic tool for analyzing the primary visual processes in vivo.
DNA Synthesis in Cultured Adult Cardiocytes
Authors: Cantin Marc , Ballak Marie , Beuzeron-Mangina Joëlle , Anand-Srivastava Madhu B. , Tautu Constantin
Published: October 2006

Trypsin-dissociated atrial cardiocytes from adult rats were exposed to [
3
H]thymidine for sequential 24-hour periods from day 2 to day 12 of culture. On day 3 and each day thereafter, cells were prepared for ultrastructural radioautography and examined with an electron microscope. Maximal incorporation occurred on day 5, when 63 percent of the cardiocytes were labeled. Mitotic activity was never present in more than 0.5 percent of the cardiocytes examined. Incorporation of [
3
H]thymidine and mitosis occurred only in immature cardiocytes characterized by subsarcolemmal primary filaments and Z bands with or without specific granules; more mature cardiocytes were never labeled.
Phase Locking, Period-Doubling Bifurcations, and Irregular Dynamics in Periodically Stimulated Cardiac Cells
Authors: Guevara Michael R. , Glass Leon , Shrier Alvin
Published: October 2006

The spontaneous rhythmic activity of aggregates of embryonic chick heart cells was perturbed by the injection of single current pulses and periodic trains of current pulses. The regular and irregular dynamics produced by periodic stimulation were predicted theoretically from a mathematical analysis of the response to single pulses. Period-doubling bifurcations, in which the period of a regular oscillation doubles, were predicted theoretically and observed experimentally.
Spatial Adaptation of Short-Wavelength Pathways in Humans
Authors: Stromeyer C. F. , Kronauer R. E. , Madsen J. C. , Cohen M. A.
Published: October 2006

Color-selective spatial adaptation of the short-wavelength, or blue-sensitive, pathway was demonstrated. The adaptation was orientation selective and strongly monocular. Adaptation was assessed by measuring visibility thresholds for monochromatic gratings in subjects adapted to high-contrast violet gratings designed to stimulate only blue-sensitive cones. The results showed spatially selective, adaptable channels within the short-wavelength pathway.
Cellular Senescence in a Cloned Strain of Bovine Fetal Aortic Endothelial Cells
Authors: Mueller Stephen N. , Rosen Eliot M. , Levine Elliot M.
Published: October 2006

The life-span in vitro and other proliferative characteristics of a strain of endothelial cells cloned from the aorta of a fetal calf were examined. Cultures of these cells had a replicative life-span of approximately 80 cumulative population doublings. Growth rates in the logarithmic phase and plateau densities decreased as the cumulative population-doubling level increased. After approximately 65 percent of the life-span of a culture was completed, the percentage of cells that incorporated [
3
H]thymidine during a 24-hour labeling period began to decrease rapidly. The cells expressed factor VIII antigen and their intercellular borders were stainable with silver nitrate throughout the life-span of each culture. Average cellular attachment size increased more than threefold between cumulative population-doubling levels 41 and 80. The facility with which cloned strains of endothelial cells can be isolated should encourage further exploitation of this important cell culture model.
Identification of Mosquitoes of
Anopheles gambiae
Species Complex A and B by Analysis of Cuticular Components
Authors: Carlson D. A. , Service M. W.
Published: October 2006

Two important vectors of malaria in Africa,
Anopheles gambiae
and
Anopheles arabiensis
(Diptera: Culicidae), often occur sympatrically and cannot be distinguished morphologically. A chemical method was developed to identify individual laboratory-reared adult males or females of either species by extraction and analysis of cuticular components with gas chromatography. Statistically significant differences were seen between species when selected pairs of peaks were compared.
Cross-Linking of Lens Crystallins in a Photodynamic System: A Process Mediated by Singlet Oxygen
Authors: Goosey John D. , Zigler J. Samuel , Kinoshita Jin H.
Published: October 2006

In a dye-sensitized photooxidation system, lens crystallin polypeptides become cross-linked, and a blue fluorescence that is associated with the proteins is produced. These changes are similar to those seen in vivo in the aging human lens. Evidence implicating singlet oxygen as the causative agent of the effects in vitro is presented, and the possibility that this species may play a role in aging and cataractogenesis in vivo is discussed.
Resources, Population, Environment: An Oversupply of False Bad News
Authors: Simon Julian L.
Published: October 2006

False bad news about population growth, natural resources, and the environment is published widely in the face of contradictory evidence. For example, the world supply of arable land has actually been increasing, the scarcity of natural resources including food and energy has been decreasing, and basic measures of U.S. environmental quality show positive trends. The aggregate data show no long-run negative effect of population growth upon the standard of living. Models that embody forces omitted in the past, especially the influence of population size upon productivity increase, suggest a long-run positive effect of additional people.
Excitatory and Inhibitory Effects of Serotonin on Sensorimotor Reactivity Measured with Acoustic Startle
Authors: Davis Michael , Strachan David I. , Kass Elizabeth
Published: October 2006

Serotonin infused into the lateral ventricle in rats produced a dose-dependent depression of the acoustic startle reflex. When infused onto the spinal cord, serotonin produced a dose-dependent increase in startle. Thus the same neurotransmitter can modulate the same behavior in opposite ways, depending on which part of the central nervous system is involved.
Calicivirus Pathogenic for Swine: a New Serotype Isolated from Opaleye
Girella nigricans
, an Ocean Fish
Authors: Smith Alvin W. , Skilling Douglas E. , Dardiri Amid H. , Latham Arthur B.
Published: October 2006

A new calicivirus, designated San Miguel sea lion virus type 7 (SMSV-7), was isolated from fish and produced a disease condition identical to vesicular exanthema in experimentally infected swine. Serotype SMSV-7 was also isolated from four elephant seals and one sea lion trematode, whereas a second calicivirus serotype isolated from fish proved to be SMSV-6.
Gastrin Injected into the Lateral Hypothalamus Stimulates Secretion of Gastric Acid in Rats
Authors: Tepperman Barry L. , Evered Mark D.
Published: October 2006

Intrahypothalamic injections of 100 picomoles of pentagastrin or natural gastrin promptly increased secretion of gastric acid in conscious rats. The response was blocked by atropine and by vagotomy. The same doses, injected intravenously or into other forebrain sites, did not increase secretion, nor did intrahypothalamic injections of other peptides common to the gut and brain.
Neural Basis of Rhythmic Behavior in Animals
Authors: Delcomyn Fred
Published: October 2006

Timing of the repetitive movements that constitute any rhythmic behavior is regulated by intrinsic properties of the central nervous system rather than by sensory feedback from moving parts of the body. Evidence of this permits resolution of the long-standing controversy over the neural basis of rhythmic behavior and aids in the identification of this mechanism as a general principle of neural organization applicable to all animals with central nervous systems.
Naegleria fowleri
: Trimethoprim Sensitivity
Authors: Červa Lubor
Published: October 2006

Trimethoprim in a concentration of 4 micrograms per milliliter of Bacto-Casitone (Difco) medium inhibits the growth of nonvirulent
Naegleria fowleri
isolates. The growth of virulent strains is unaffected even with 400 micrograms of the drug per milliliter of medium. Differences in sensitivity constitute the possibility of a simple selection of environmental isolates. The pathogenicity and virulence of
Naegleria
species may be connected with the metabolism of folic acid.
Mood and Behavioral Effects of Physostigmine on Humans Are Accompanied by Elevations in Plasma β-Endorphin and Cortisol
Authors: Risch Samuel C. , Cohen Robert M. , Janowsky David S. , Kalin Ned H. , Murphy Dennis L.
Published: October 2006

Administration of physostigmine to normal volunteers produced significant elevations in plasma cortisol and β-endorphin immunoreactivity as well as alterations in mood, cognition, and behavior. These observations might be explained by a cholinergically mediated stress syndrome. However, peak elevations in plasma β-endorphin immunoreactivity (but not in plasma cortisol) were significantly correlated with physostigmine-induced increases in depression ratings. These results suggest that a cholinergically mediated β-endorphin pathway may be involved in the observed affective changes.
Metabolism of Propachlor by the Germfree Rat
Authors: Bakke Jerome E. , Gustafsson Jan-Åke , Gustafsson Bengt E.
Published: October 2006

Three major metabolites of propachlor were isolated from the excreta of germfree rats given
14
C-labeled propachlor orally. In contrast, 11 urinary metabolites, six of which were 2-methylsulfonylacetanilides not present in excreta of germfree rats, were isolated from control rats given
14
C-labeled propachlor orally. Enterohepatic circulation and microbial metabolism in the intestine were necessary for production of the methylsulfonyl-containing and other metabolites of propachlor in the conventional rat.
Calcofluor White ST Alters the in Vivo Assembly of Cellulose Microfibrils
Authors: Haigler Candace H. , Brown R. Malcolm , Benziman M.
Published: October 2006

The fluorescent brightener, Calcofluor White ST, prevents the in vivo assembly of crystalline cellulose microfibrils and ribbons by Acetobacter xylinum. In the presence of more than 0.01 percent Calcofluor, Acetobacter continues to synthesize high-molecular-weight β-1,4 glucans. X-ray crystallography shows that the altered product exhibits no detectable crystallinity in the wet state, but upon drying it changes into crystalline cellulose I. Calcofluor alters cellulose crystallization by hydrogen bonding with glucan chains. Synthesis of this altered product is reversible and can be monitored with fluorescence and electron microscopy. Use of Calcofluor has made it possible to separate the processes of polymerization and crystallization leading to the biogenesis of cellulose microfibrils, and has suggested that crystallization occurs by a cell-directed, self-assembly process in
Acetobacter xylinum
.
Human Sleep: Its Duration and Organization Depend on Its Circadian Phase
Authors: Czeisler Charles A. , Weitzman Elliot D. , Moore-Ede Martin C. , Zimmerman Janet C. , Knauer Richard S.
Published: October 2006

Two- to threefold variations in sleep length were observed in 12 subjects living on self-selected schedules in an environment free of time cues. The duration of polygraphically recorded sleep episodes was highly correlated with the circadian phase of the body temperature rhythm at bedtime and not with the length of prior wakefulness. Furthermore, the rate of REM (rapid eye movement) sleep accumulation, REM latency, bedtime selection, and self-rated alertness assessments were also correlated with the body temperature rhythm.
Lactose Facilitates the Intestinal Absorption of Lead in Weanling Rats
Authors: Bushnell Philip J. , DeLuca Hector F.
Published: October 2006

The milk sugar lactose is known to facilitate calcium absorption and has been shown to enhance the uptake of essential trace metals from the intestines as well. Its physiological role as the major carbohydrate source for suckling mammals is thus complemented by its ability to facilitate the absorption of necessary minerals. The studies reported here show that the intestinal absorption of lead and its uptake into blood, liver, kidney, and bone are also increased by lactose in young weanling rats. These data extend the known range of lactose facilitation of mineral absorption to a nonessential, toxic element, confirming the nonspecificity of its action on the gut. In addition, they suggest an explanation for some of the conflicting evidence regarding the prophylactic efficacy of milk in lead poisoning.
Associative Learning in
Aplysia
: Cellular Correlates Supporting a Conditioned Fear Hypothesis
Authors: Carew Thomas J. , Walters Edgar T. , Kandel Eric R.
Published: October 2006

Aversive associative learning in
Aplysia californica
survives restraint of the animal and surgical exposure of the central nervous system. The learning is expressed in the intracellularly recorded activity of identified motor neurons mediating three different defensive behaviors: escape locomotion, inking, and siphon withdrawal. In each case, animals that had previously received paired training showed significant facilitation of synaptic input to motor neurons during test stimulation in the presence of the conditioned stimulus. Animals without such training showed no facilitation of input to the motor neurons. Resting potential and input resistance appeared unaffected by conditioning and were not altered by application of the conditioned stimulus. These results show that the conditioned facilitation of defensive responses cannot be explained by subthreshold actions of the conditioned stimulus on the motor neurons and support the hypothesis that
Aplysia
learn to associate the conditioned stimulus with a fearlike central state.
Auditory Brainstem Potentials in Chronic Alcoholics
Authors: Begleiter H. , Porjesz B. , Chou C. L.
Published: October 2006

Auditory brainstem potentials were recorded from abstinent chronic alcoholics and control subjects. The latencies of peaks II, III, IV, and V were significantly delayed in the alcoholic patients compared to control subjects. Brainstem transmission time was longer in alcoholics than in controls. This study provides systematic evidence that chronic alcohol abuse results in brainstem deficits suggesting possible demyelination of auditory tracts.
Rapid Correction of Hyponatremia Causes Demyelination: Relation to Central Pontine Myelinolysis
Authors: Kleinschmidt-DeMasters B. K. , Norenberg Michael D.
Published: October 2006

The human demyelinative disorder central pontine myelinolysis may be an iatrogenic disease caused by a rapid rise in serum sodium, usually when hyponatremia is corrected. Rats treated with hypertonic saline after 3 days of vasopressin-induced hyponatremia had demyelinative lesions in the corpus striatum, lateral hemispheric white matter, cerebral cortex, hippocampal fimbria, anterior commissure, thalamus, brainstem tegmentum, and cerebellum. Thus, rapid correction of hyponatremia can lead to demyelinative lesions and may be the cause of central pontine myelinolysis in man.
Repair of the Ultraviolet-Irradiated Male Genome in Fertilized Mouse Eggs
Authors: Brandriff Brigitte , Pedersen Roger A.
Published: October 2006

Unscheduled DNA synthesis occurred in both male and female pronuclei of the mouse zygote in response to irradiation with ultraviolet light, indicating a capacity for excision repair. Furthermore, damage to DNA of the male gamete before fertilization can be repaired after the sperm enters the egg cytoplasm.
Noise Raises Blood Pressure Without Impairing Auditory Sensitivity
Authors: Peterson E. A. , Augenstein J. S. , Tanis D. C. , Augenstein D. G.
Published: October 2006

Two rhesus monkeys, exposed continuously to realistic patterns and levels of noise for 9 months, exhibited sustained elevations in blood pressure that did not return to baseline values after the noise ended. Auditory brainstem responses, measured before and after exposure, indicated no change in auditory sensitivity.
Detection of Mutagenic Activity of Metronidazole and Niridazole in Body Fluids of Humans and Mice
Authors: Legator Marvin S. , Connor Thomas H. , Stoeckel Marie
Published: October 2006

After humans were treated at therapeutic doses with the trichomonacide metronidazole (Flagyl) and the antischistosomal agent niridazole mutagenic activity was demonstrable in their urines when tested with the histidine auxotroph of
Salmonella typhimurium
. Both compounds were active in the host-mediated assay in mice, and evidence of activity was found in the blood and urine of mice treated with niridazole but not with metronidazole.
An Unnatural Biopolymer
Authors: Cho Charles Y. , Moran Edmund J. , Cherry Sara R. , Stephans James C. , Fodor Stephen P. A. , Adams Cynthia L. , Sundaram Arathi , Jacobs Jeffrey W. , Schultz Peter G.
Published: October 2006

A highly efficient method has been developed for the solid-phase synthesis of an "unnatural biopolymer" consisting of chiral aminocarbonate monomers linked via a carbamate backbone. Oligocarbamates were synthesized from
N
-protected
p
-nitrophenyl carbonate monomers, substituted with a variety of side chains, with greater than 99 percent overall coupling efficiencies per step. A spatially defined library of oligocarbamates was generated by using photochemical methods and screened for binding affinity to a monoclonal antibody. A number of high-affinity ligands were then synthesized and analyzed in solution with respect to their inhibition concentration values, water/octanol partitioning coefficients, and proteolytic stability. These and other unnatural polymers may provide new frameworks for drug development and for testing theories of protein and peptide folding and structure.
Major Groove Accessibility of RNA
Authors: Weeks Kevin M. , Crothers Donald M.
Published: October 2006

Chemical acylation experiments showed that the RNA major groove, often assumed to be too deep and narrow to permit recognition interactions, is accessible at duplex termini. Reactivity extended further into the helix in the 5′ than in the 3′ direction. Asymmetric and large loops between helices uncoupled them, which yielded both enhanced reactivity at terminal base pairs and weaker stabilization enthalpy compared to that in small loops or symmetric loops of the same size. Uncoupled helices have effective helix ends with accessible major grooves; such motifs are attractive contributors to protein recognition, tertiary folding, and catalysis.
Inhibition by cAMP of Ras-Dependent Activation of Raf
Authors: Cook Simon J. , McCormick Frank
Published: October 2006

Activation of the Raf and extracellular signal-regulated kinases (ERKs) (or mitogen-activated protein kinases) are key events in mitogenic signaling, but little is known about interactions with other signaling pathways. Agents that raise levels of intracellular cyclic adenosine 3′,5′-monophosphate (cAMP) blocked DNA synthesis and signal transduction in Rat1 cells exposed to epidermal growth factor (EGF) or lysophosphatidic acid. In the case of EGF, receptor tyrosine kinase activity and association with the signaling molecules Grb2 and Shc were unaffected by cAMP. Likewise, EGF-dependent accumulation of the guanosine 5′-triphosphate-bound form of Ras was unaffected. In contrast, activation of Raf-1 and ERK kinases was inhibited. Thus, cAMP appears to inhibit signal transmission from Ras by preventing Ras-dependent activation of Raf-1.
Human Pancreatic Islets in Culture: Effects of Supplementing the Medium with Homologous and Heterologous Serum
Authors: Goldman H. , Colle E.
Published: October 2006

Islets of Langerhans, isolated from the human fetal pancreas and cultured in media supplemented with serums from human umbilical cord or adult donors, remained intact, free-floating, and functional for 2 to 5 months. Substitution of fetal calf serum for the human serum usually resulted in attachment of islets, monolayer formation, and relatively early (3 weeks) functional arrest.
Human Malaria Parasites in Continuous Culture
Authors: Trager William , Jensen James B.
Published: October 2006

Plasmodium falciparum
can now be maintained in continuous culture in human erythrocytes incubated at 38°C in RPMI 1640 medium with human serum under an atmosphere with 7 percent carbon dioxide and low oxygen (1 or 5 percent). The original parasite material, derived from an infected
Aotus trivirgatus
monkey, was diluted more than 100 million times by the addition of human erythrocytes at 3- or 4-day intervals. The parasites continued to reproduce in their normal asexual cycle of approximately 48 hours but were no longer highly synchronous. They have remained infective to
Aotus
.
Titanium (III) Citrate as a Nontoxic Oxidation-Reduction Buffering System for the Culture of Obligate Anaerobes
Authors: Zehnder Alexander J. B. , Wuhrmann Karl
Published: October 2006

An oxidation-reduction buffering system based on titanium(III) citrate eliminates any traces of oxygen in a culture medium, serves as an indicator for low oxidation-reduction potentials, and prevents the growth of facultative anaerobes, which frequently contaminate anaerobic cultures.
Attachment of
Helicobacter pylori
to Human Gastric Epithelium Mediated by Blood Group Antigens
Authors: Borén Thomas , Falk Per , Roth Kevin A. , Larson Göran , Normark Staffan
Published: October 2006

Helicobacter pylori
is associated with development of gastritis, gastric ulcers, and adenocarcinomas in humans. The Lewis
b
(Le
b
) blood group antigen mediates
H. pylori
attachment to human gastric mucosa. Soluble glycoproteins presenting the Le
b
antigen or antibodies to the Le
b
antigen inhibited bacterial binding. Gastric tissue lacking Le
b
expression did not bind
H. pylori
. Bacteria did not bind to Le
b
antigen substituted with a terminal GalNAcα1-3 residue (blood group A determinant), suggesting that the availability of
H. pylori
receptors might be reduced in individuals of blood group A and B phenotypes, as compared with blood group O individuals.
Gene Transfer to Myxobacterium by
Escherichia coli
Phage P1
Authors: Kaiser Dale , Dworkin Martin
Published: October 2006

Myxococcus xanthus
is a bacterium with an interest for studies of development because it has an organized multicellular phase in its life cycle. Bacteriophage P1 can adsorb to
M. xanthus
and inject its DNA into this organism despite the wide taxonomic gap separating myxococcus from
Escherichia coli
, the source of P1. A specialized transducing derivative of P1, called P1CM, can carry a gene for chloramphenicol resistance from
E. coli
into
M. xanthus
and generate unstable drug-resistant strains.
Control Factor of Nuclear Cycles in Ciliate Conjugation: Cell-to-Cell Transfer in Multicellular Complexes
Authors: Miyake Akio
Published: October 2006

Multicellular complexes of
Blepharisma intermedium
are regularly produced by treating doublet cells with the gamone of complementary mating type. Cells remain united without undergoing nuclear cycles of conjugation. However, if a cell of complementary mating type unites, nuclear cycles begin at the site of this union and propagate all through the multicellular complex.
Chlorinated Hydrocarbon Pollutants and Photosynthesis of Marine Phytoplankton: A Reassessment
Authors: Fisher Nicholas S.
Published: October 2006

The chlorinated hydrocarbons DDT and PCB's (polychlorinated biphenyls), ubiquitous pollutants of the marine environment, have been observed to reduce the cell division rate of marine phytoplankton, thereby indirectly reducing the total photosynthetic carbon fixation in treated cultures. The photosynthetic capacity of each cell was not affected. Total marine photosynthesis will likely remain undiminished by these compounds, although alterations in phytoplankton communities through selective toxicity could affect herbivore populations.
Taxol and Taxane Production by
Taxomyces andreanae
, an Endophytic Fungus of Pacific Yew
Authors: Stierle Andrea , Strobel Gary , Stierle Donald
Published: October 2006

Taxomyces andreanae
, a fungal endophyte, was isolated from the phloem (inner bark) of the Pacific yew,
Taxus brevifolia
. The fungus is hyphomyceteous and, when grown in a semi-synthetic liquid medium, produced taxol and related compounds. Taxol was identified by mass spectrometry, chromatography, and reactivity with monoclonal antibodies specific for taxol. Both [1-
14
C]acetic acid and L-[U-
14
C]phenylalanine served as precursors of [
14
C]taxol in fungal cultures. No taxol was detected in zero-time cultures or in the small agar plugs used to inoculate the culture flasks.
Development of T
H
1 CD4
+
T Cells Through IL-12 Produced by
Listeria
-Induced Macrophages
Authors: Hsieh Chyi-Song , Macatonia Steven E. , Tripp Catherine S. , Wolf Stanley F. , O'Garra Anne , Murphy Kenneth M.
Published: October 2006

Development of the appropriate CD4
+
T helper (T
H
) subset during an immune response is important for disease resolution. With the use of naive, ovalbumin-specific αβ T cell receptor transgenic T cells, it was found that heat-killed
Listeria monocytogenes
induced T
H
1 development in vitro through macrophage production of interleukin-12 (IL-12). Moreover, inhibition of macrophage production of IL-12 may explain the ability of IL-10 to suppress T
H
1 development. Murine immune responses to
L. monocytogenes
in vivo are of the appropriate T
H
1 phenotype. Therefore, this regulatory pathway may have evolved to enable innate immune cells, through interactions with microbial pathogens, to direct development of specific immunity toward the appropriate T
H
phenotype.
The Role of T
H
1 and T
H
2 Cells in a Rodent Malaria Infection
Authors: Taylor-Robinson Andrew W. , Phillips R. Stephen , Severn Alison , Moncada Salvador , Liew Foo Y.
Published: October 2006

CD4
+
T cells play a major role in protective immunity against the blood stage of malaria, but the mechanism of protection is unclear. By adoptive transfer of cloned T cell lines, direct evidence is provided that both T
H
1 and T
H
2 subsets of CD4
+
T cells can protect mice against
Plasmodium chabaudi chabaudi
infection. T
H
1 cells protect by a nitric oxide-dependent mechanism, whereas T
H
2 cells protect by the enhancement and accelerated production of specific immunoglobulin G1 antibody.
A Transglutaminase That Converts Interleukin-2 into a Factor Cytotoxic to Oligodendrocytes
Authors: Eitan Shoshana , Schwartz Michal
Published: October 2006

Regenerating optic nerves from fish produce a factor that is cytotoxic to oligodendrocytes. The cytotoxic factor is recognized by antibodies to interleukin-2 (IL-2) and has the apparent molecular size of a dimer of IL-2. An enzyme, identified as a nerve transglutaminase, was purified from regenerating optic nerves of fish and was found to catalyze dimerization of human IL-2. The dimerized IL-2, unlike monomeric IL-2, is cytotoxic to oligodendrocytes from rat brain in culture. The results suggest that posttranslational modification of a cytokine can alter its activity. Under conditions in which oligodendrocytes inhibit neuronal regeneration, dimerization of IL-2 might provide a mechanism to permit nerve growth.
Anatomical Study of Cerebral Asymmetry in the Temporal Lobe of Humans, Chimpanzees, and Rhesus Monkeys
Authors: Yeni-Komshian Grace H. , Benson Dennis A.
Published: October 2006

It is generally accepted that anatomical asymmetries in the temporal lobe language region of humans are associated with the asymmetrical representation of language function in the left hemisphere. Comparative measurements were taken of the length of the left and right Sylvian fissures of human, chimpanzee, and rhesus monkey brains. Measurements confirmed the findings of other studies that the human Sylvian fissure is longer on the left than on the right. The chimpanzee brains had a similar asymmetry but to a lesser degree than the human brains. The rhesus brains, however, showed no significant differences between left and right fissure lengths.
Cross-Modal Matching and the Primate Frontal Cortex
Authors: Petrides M. , Iversen Susan D.
Published: October 2006

Rhesus monkeys with selective lesions of the prefrontal system were tested on a tactile-visual cross-modal matching task. Monkeys with lesions in the banks and depths of the arcuate sulcus were impaired, while normal controls and monkeys with lesions in the banks and depths of the sulcus principalis and in the anterodorsal part of the head of the caudate nucleus were not.
Ribonucleotide Reductase in Blue-Green Algae: Dependence on Adenosylcobalamin
Authors: Gleason F. K. , Wood J. M.
Published: October 2006

Ten species of freshwater blue-green algae exhibit an adenosylcobalamin-dependent ribonucleotide reductase, thus explaining the requirement for cobalt by these organisms. The evidence suggests a phylogenetic affinity between the cyanophytes and bacteria, such as
Clostridium
and
Rhizobium
, and the euglenoid flagellates, which also use the cofactor-dependent reductase. In contrast, the ribonucleotide reductase reaction in the few green algae surveyed shows no dependence on cobalamins.
Control of the
exo
and
endo
Pathways of the Diels-Alder Reaction by Antibody Catalysis
Authors: Gouverneur Veronique E. , Houk K. N. , de Pascual-Teresa Beatriz , Beno Brett , Janda Kim D. , Lerner Richard A.
Published: October 2006

Catalytic antibodies that control the reaction pathways of the Diels-Alder cycloaddition have been generated. One antibody catalyzes the favored
endo
and the other the disfavored
exo
pathway to yield the respective
cis
and
trans
adducts in enantiomerically pure form. A comparison of the x-ray structure of the hapten with the calculated geometry of the transition structure showed that [2.2.2] bicyclic compounds are excellent mimics of the transition state of the Diels-Alder reaction. To achieve catalysis and the high degree of stereoselectivity shown here, the antibody must simultaneously control the conformation of the individual reactants and their relation to each other. In the case of the disfavored process, binding energy must be used to reroute the reaction along a higher energy pathway. The rerouting of reaction pathways has become a major focus of antibody catalysis and other disfavored reactions can be expected to be catalyzed so long as the energy barrier is not extreme. The energy requirements needed for absolute control of all of the stereoisomers of many Diels-Alder reactions fall in the energy range (∼20 kilocalories per mole) deliverable by antibody binding.
Structure-Based Design of a Cyclophilin-Calcineurin Bridging Ligand
Authors: Alberg David G. , Schreiber Stuart L.
Published: October 2006

The affinity of a flexible ligand that adopts a specific conformation when bound to its receptor should be increased with the appropriate use of conformational restraints. By determining the structure of protein-ligand complexes, such restraints can in principle be designed into the bound ligand in a rational way. A tricyclic variant (TCsA) of the immunosuppressant cyclosporin A (CsA), which inhibits the proliferation of T lymphocytes by forming a cyclophilin-CsA-calcineurin complex, was designed with the known three-dimensional structure of a cyclophilin-CsA complex. The conformational restraints in TCsA appear to be responsible for its greater affinity for cyclophilin and calcineurin relative to CsA.
Converting Tissue Plasminogen Activator to a Zymogen: A Regulatory Triad of Asp-His-Ser
Authors: Madison Edwin L. , Kobe Andreja , Gething Mary-Jane , Sambrook Joseph F. , Goldsmith Elizabeth J.
Published: October 2006

Unlike most serine proteases of the chymotrypsin family, tissue-type plasminogen activator (tPA) is secreted from cells as an active, single-chain enzyme with a catalytic efficiency only slightly lower than that of the proteolytically cleaved form. A zymogenic mutant of tPA has been engineered that displays a reduction in catalytic efficiency by a factor of 141 in the single-chain form while retaining full activity in the cleaved form. The residues introduced in the mutant, serine 292 and histidine 305, are proposed to form a hydrogen-bonded network with aspartate 477, similar to the aspartate 194-histidine 40-serine 32 network found to stabilize the zymogen chymotrypsinogen.