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T Nelson

Publications and source records attributed to T Nelson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Pet-1, a novel ETS domain factor that can activate neuronal nAchR gene transcription.

We report a cDNA clone prepared from adrenal chromaffin-derived PC12 cell RNA that encodes a novel ETS-domain factor, Pet-1. The deduced primary structure of Pet-1 is composed of 340 amino acids and the encoded polypeptide has a predicted molecular mass of 35.4 kD. The pattern of Pet-1 gene expression in the neonatal rat is highly restricted and suggests that Pet-1 functions primarily in the nervous system. Adrenal gland expresses the highest level of Pet-1 among the tissues examined. In situ hybridization indicates that Pet-1 is expressed in the adrenal medulla but not the adrenal cortex. Slightly weaker Pet-1 hybridization is detected in brain and low levels are detectable in intestine and eye. Pet-1 can bind specifically to a PEA3 ETS DNA-binding motif and can modulate transcription of synthetic promoter constructs in a sequence-specific manner. We recently identified a neural cell-type specific enhancer, beta43', within the 3'-untranslated exon of the neuronal nicotinic acetylcholine receptor (nAchR) beta4 subunit gene. Similar to Pet-1, the beta4 gene is also expressed in PC12 cells. The presence of putative ETS-domain binding sites in the beta43' enhancer led us to hypothesize that members of the ets gene family activate neuronal nAchR genes. Cotransfection assays show that Pet-1 can activate reporter gene transcription in a beta43' enhancer-dependent and cell type-dependent manner. Our results lead us to hypothesize that Pet-1 acts as a transcriptional regulator of downstream target genes involved in cholinergic neurotransmission.

Amino Acid Sequence↗
PubMed1998

Regulation of connexin43 expression and function by prostaglandin E2 (PGE2) and parathyroid hormone (PTH) in osteoblastic cells.

Connexin43 (Cx43) forms gap junctions that mediate intercellular communication between osteoblasts. We have examined the effects of prostaglandin E2 (PGE2) and parathyroid hormone (PTH) on gap junctional communication in the rat osteogenic sarcoma cells UMR 106-01. Incubation with either PGE2 or PTH rapidly (within 30 min) increased transfer of negatively charged dyes between UMR 106-01 cells. This stimulatory effect lasted for at least 4 h. Both PGE2 and PTH increased steady-state levels of Cx43 mRNA, but only after 2-4 h of incubation. Transfection with a Cx43 gene construct linked to luciferase showed that this effect of PTH was the result of transcriptional upregulation of Cx43 promoter. Stimulation of dye coupling and Cx43 gene transcription were reproduced by forskolin and 8Br-cAMP. Exposure to PGE2 for 30 min increased Cx43 abundance at appositional membranes in UMR 106-01, whereas total Cx43 protein levels increased only after 4-6 h of incubation with either PGE2 or PTH. Inhibition of protein synthesis by cycloheximide did not affect this early stimulation of dye coupling, but it significantly inhibited the sustained effect of PTH and forskolin on cell coupling. In summary, both PTH and PGE2, presumably through cAMP production, enhance gap junctional communication in osteoblastic cell cultures via two mechanisms: initial rapid redistribution of Cx43 to the cell membrane, and later stimulation of Cx43 gene expression. Modulation of intercellular communication represents a novel mechanism by which osteotropic factors regulate the activity of bone forming cells.

Animals↗
PubMed1998

Evolution of adaptive neural networks: the role of voltage-dependent K+ channels.

The vestibular pathway of the mollusk Hermissenda crassicornis mediates a reflexive, unconditioned response to disorientation, clinging, that has been conserved during evolution even to the emergence of our own species. This response becomes associated with a visual stimulus (mediated by a precisely ordered visual-vestibular synaptic network) according to principles of Pavlovian conditioning that are also followed in human learning. It is not entirely surprising therefore that molecular and biophysical cascades responsible for this associative learning appear to function in both mollusks and mammals. In brief, combinational elevation of (Ca2+)i, diacylglycerol, and arachidonic acid activates protein kinase C to phosphorylate the Ca2+ and guanosine triphosphate-binding protein, cp20 (now called calexcitin (Nelson T, et al. Proc Natl Acad Sci USA 1996;93:13808-13)), which potently inactivates postsynaptic voltage-dependent K+ currents and thereby increases synaptic weight. Longer term changes included rearrangement of synaptic terminals and modified protein synthesis. This cascade has also been implicated in other associative-learning paradigms (e.g., spatial maze, olfactory discrimination) and as a pathophysiologic target in early Alzheimer's disease. Recent molecular biologic experiments also demonstrate the dependence of associative memory (but not long-term potentiation) on voltage-dependent K+ currents. Theoretic learning models based on these findings focus on dendritic spine clusters and yield computer implementations with powerful pattern-recognition capabilities.

Adaptation, Physiological↗
PubMed1998

Leafbladeless1 is required for dorsoventrality of lateral organs in maize.

The maize leafbladeless1 (lbl1) mutant displays a variety of leaf and plant phenotypes. The most extreme manifestation in the leaf is the formation of radially symmetric, abaxialized leaves due to a complete loss of adaxial cell types. Less severe phenotypes, resulting from a partial loss of adaxial cell identity, include the formation of ectopic laminae at the boundary between abaxialized, mutant sectors on the adaxial leaf surface and the bifurcation of leaves. Ectopic laminae and bifurcations arise early in leaf development and result in an altered patterning of the leaf along the proximodistal axis, or in complete duplication of the developing organ. Leaf-like lateral organs of the inflorescences and flowers show similar phenotypes. These observations suggest that Lbl1 is required for the specification of adaxial cell identity within leaves and leaf-like lateral organs. Lbl1 is also required for the lateral propagation of leaf founder cell recruitment, and plays a direct or indirect role in the downregulation of the homeobox gene, knotted1, during leaf development. Our results suggest that adaxial/abaxial asymmetry of lateral organs is specified in the shoot apical meristem, and that formation of this axis is essential for marginal, lateral growth and for the specification of points of proximodistal growth. Parallels between early patterning events during lateral organ development in plants and animals are discussed.

Alleles↗
PubMed1998

Reducing risks to children in vehicles with passenger airbags.

This review examines the risk that passenger airbags pose for children and discusses behavioral and technologic measures aimed at protecting children from airbag deployment. Although airbags reduce fatal crash injuries among adult drivers and passengers, this safety technology increases mortality risk among children younger than age 12. The magnitude of the risk is multiplied when children are unrestrained or restrained improperly. As new vehicles are resold to buyers who tend to be less safety-conscious than new car owners, the number of children endangered by passenger airbag deployment may increase. For vehicles already in the fleet, strong measures are required to secure children in the rear seat and increase the proper use of appropriate restraint systems through police enforcement of laws. One promising strategy is to amend child passenger safety laws to require that parents secure children in the rear seats. For future vehicles, a mandatory performance standard should be adopted that suppresses airbag deployment automatically if a child is located in the front passenger seat. Other promising improvements in airbag design also are discussed. Major changes in passenger airbag design must be evaluated in a broad analytical framework that considers the welfare of adults as well as children.

Adult↗
PubMed1996

Field performance measurements of half-facepiece respirators--foundry operations.

A series of field studies was conducted to measure workplace protection factors (WPF) provided by elastomeric and disposable half-facepiece respirators against different particulate contaminants. The research protocol developed for the study has been described in a previous article. This article presents results from dust and fume exposures at three foundries. The major components of the airborne exposures in these foundries were zinc, lead, and silicon. The major components of the in-facepiece samples were zinc, chlorine, and lead. Significant differences were observed in ambient zinc and lead concentration levels among foundries; however, no significant difference was observed in the in-facepiece concentrations of these elements among foundries. Respirator performance varied within each foundry, but there was no difference in performance when pooling all foundry data. The 5th, 10th and 50th percentile estimates for the pooled foundry and respirator WPF data were about 9, 16, and 114 respectively. The infacepiece concentration data clearly indicate that dust-fume-mist (DFM) class half-facepiece respirators, when conscientiously used, worn, and maintained, in conjunction with other existing controls in these foundries, provided effective worker protection.

Aerosols↗
PubMed1996

Leaf permease1 gene of maize is required for chloroplast development.

Adjacent bundle sheath and mesophyll cells cooperate for carbon fixation in the leaves of C4 plants. Mutants with compromised plastid development should reveal the degree to which this cooperation is obligatory, because one can assay whether mesophyll cells with defective bundle sheath neighbors retain C4 characteristics or revert to C3 photosynthesis. The leaf permease1-mutable1 (lpe1-m1) mutant of maize exhibits disrupted chloroplast ultrastructure, preferentially affecting bundle sheath choroplasts under lower light. Despite the disrupted ultrastructure, the metabolic cooperation of bundle sheath and mesophyll cells for C4 photosynthesis remains intact. To investigate this novel mutation, the Activator transposon-tagged allele and cDNAs corresponding to the Lpe1 mRNA from wild-type plants were cloned. The Lpe1 gene encodes a polypeptide with significant similarity to microbial pyrimidine and purine transport proteins. An analysis of revertant sectors generated by Activator excision suggests that the Lpe1 gene product is cell autonomous and can be absent up to the last cell divisions in the leaf primordium without blocking bundle sheath chloroplast development.

Amino Acid Sequence↗
PubMed1996

Mixed neuronal-glial tumors (gangliogliomas) in children.

Mixed tumors account for about 10% of the childhood central nervous system tumors. Studies of the most common tumor, the ganglioglioma, in patients of all ages suggest that optimal therapy is total gross resection. There are few studies on these tumors in children. In our institution between 1984 and 1993, 28 children with gangliogliomas (4 of which were anaplastic) and 4 children with dysembryoplastic neuroepithelial tumors were treated and followed. Fourteen had local subarachnoid involvement. Total gross resection was usually curative, regardless of histology. Subarachnoid involvement was not indicative of a poorer prognosis.

Adolescent↗
PubMed1996

Abnormalities of ICP loudness adaptation at 1000 Hz associated with higher frequency (cochlear) loss.

Individuals with higher frequency hearing loss, when tested at 1000 Hz, showed more loudness adaptation at 40 dB HL and less at 60 dB HL (ISO) than the normal listeners. Adaptation was measured with the monaural method described by Weiler, Sandman and Pederson (1981), now called the Ipsilateral Comparison Paradigm (ICP) by Dange et al. (1993). Using the same method Korman (1986) had shown that a complex combination of stimulus conditions, including intensity, produced differences between a similar group with high frequency hearing loss and normals. The current results confirm the value of this method for studying adnormalities in the loudness function at middle intensities. Because it is a quick and reliable method we believe it has potential for clinical use but acknowledge considerable research and development is necessary.

Aged↗
PubMed1995

Imaging protein kinase C activation in living sea urchin eggs after fertilization.

The fluorescent dye NBD-phorbol acetate was used to visualize the activation of protein kinase C (PKC) in living Lytechinus pictus eggs during fertilization. The dye interacts directly with PKC as determined using a competitive binding assay. Quantitative image analysis of sequential images from laser-scanning confocal microscopy showed a significant reorganization of the signal in the vicinity of the cortical granules and the plasma membrane that began immediately following fertilization and persisted up to 1 hr (P<0.0001). At the concentrations employed, the NBD-phorbol dye was not capable of inducing a significant translocation of the fluorescent signal to the membrane, nor did it appear to interfere with the cell cycle. It therefore seems likely that the present in vivo results reflect the previously reported in vitro activation of protein kinase C immediately subsequent to fertilization. Such an interpretation is parsimonious with the results of parallel subcellular fractionation experiments using an N-terminal polyclonal antibody to sea urchin PKC which showed a significant (P<0.037) translocation of the enzyme from the cytosolic fraction to the membrane fraction 40 min subsequent to fertilization. This study supports and extends previous in vitro data suggesting that PKC activation subsequent to fertilization occurs at or near the egg plasma membrane, perhaps in association with arachadonic acid-rich cortical granules.

Animals↗
PubMed1995

C4 isoform of NADP-malate dehydrogenase. cDNA cloning and expression in leaves of C4, C3, and C3-C4 intermediate species of Flaveria.

In C4 plants of the NADP-malic enzyme type, an abundant, mesophyll cell-localized NADP-malate dehydrogenase (MDH) acts to convert oxaloacetate, the initial product of carbon fixation, to malate before it is shuttled to the bundle sheath. Since NADP-MDH has different but important roles in leaves of C3 and C4 plants, we have cloned and characterized a nearly full-length cDNA encoding NADP-MDH from Flaveria trinervia (C4) to permit comparative structure/expression studies within the genus flaveria. The dicot genus Flaveria includes C3-C4 intermediate species, as well as C3 and C4 species. We show that the previously noted differences in NADP-MDH activity levels among C3, C4, and C3-C4 Flaveria species are in part due to interspecific differences in mRNA accumulation. We also show that the NADP-MDH gene appears to be present as a single copy among different Flaveria species, suggesting that a pre-existing gene has been reregulated during the evolution from C3 to C4 plants to accommodate the abundance and localization requirements of the C4 cycle.

Amino Acid Sequence↗
PubMed1994

Controlled Ecological Life Support Systems (CELSS) flight experimentation.

The NASA CELSS program has the goal of developing life support systems for humans in space based on the use of higher plants. The program has supported research at universities with a primary focus of increasing the productivity of candidate crop plants. To understand the effects of the space environment on plant productivity, the CELSS Test Facility (CTF) has been been conceived as an instrument that will permit the evaluation of plant productivity on Space Station Freedom. The CTF will maintain specific environmental conditions and collect data on gas exchange rates and biomass accumulation over the growth period of several crop plants grown sequentially from seed to harvest. The science requirements of the CTF will be described, as will current design concepts and specific technology requirements for operation in micro-gravity.

Crops, Agricultural↗
PubMed1994

Progesterone administration induced impairment of insulin suppression of hepatic glucose production.

OBJECTIVE: To assess whether P administration impairs insulin-mediated glucose uptake. DESIGN: Two-step euglycemic hyperinsulinemic clamp studies. SETTING: Rats studied with (n = 11) or without (n = 10) P treatment. PARTICIPANTS: Conscious, unstressed, oophorectomized female rats. MAIN OUTCOME MEASURES: Plasma glucose and insulin levels and the rates of glucose turnover results. RESULTS: Fasting glucose (115 +/- 5 versus 109 +/- 4 mg/dL; conversion factor to SI units 0.05551) and insulin (1.67 +/- 0.24 versus 1.51 +/- 0.22 ng/mL; conversion factor to SI units 174.5) levels were not significantly different in the control and P treated groups, respectively. However, the basal rate of glucose turnover was significantly higher in P-treated rats (8.38 +/- 0.50 versus 6.59 +/- 0.35 mg/kg per minute in controls. During low-dose insulin infusion (2 mU/kg per minute), there was no difference in glucose or insulin levels, or the rate of glucose utilization; however, residual hepatic glucose production was significantly greater in the P group (5.34 +/- 0.68 versus 2.57 +/- 1.00 mg/kg per minute) in controls. At high-dose insulin infusion (10 mU/kg per minute), hepatic glucose production was completely suppressed in both groups; there was no difference in insulin sensitivity as assessed by the glucose utilization rate or the ratio of glucose uptake to insulin level. CONCLUSIONS: Chronic P therapy does not alter insulin-mediated glucose utilization in peripheral tissues but does reduce the ability of insulin to suppress endogenous hepatic glucose production.

Animals↗
PubMed1994

Increases in local cerebral blood flow associated with somatosensory activation are not mediated by NO.

Effects of inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME) on the increases in local cerebral blood flow (LCBF) produced in the whisker-to-barrel sensory pathway by vibrissal stimulation were studied in conscious rats with the autoradiographic iodo[14C]antipyrine method. Unilateral whisker stroking increased LCBF in the ipsilateral trigeminal spinal and principal sensory nuclei, contralateral ventral posteromedial thalamic nucleus, and contralateral somatosensory barrel cortex. Intravenous L-NAME (30 mg/kg) lowered baseline LCBF without altering the percent increases due to stimulation. Intracisternal infusions of L-NAME in doses about 10 times the molar content of free arginine in brain inhibited brain NO synthesis activity by 88%, but the percent augmentations of LCBF by stimulation remained unchanged. Chronic treatment with L-NAME (50 mg/kg ip twice daily for 4 days) inhibited NO synthase activity in brain by 84% but also failed to reduce the percent increases in LCBF due to stimulation. These results indicate that NO does not mediate the increases in LCBF associated with functional activation.

Amino Acid Oxidoreductases↗
PubMed1994

Developmental time courses in the brain and kidney of two enzymes that oxidize gamma-hydroxybutyrate.

The postnatal developmental profiles of two enzymes that oxidize gamma-hydroxybutyrate (GHB) were examined during the period when the brain concentration of GHB was changing from the higher fetal level (7 microM) to the lower adult level (2 microM). At 20 days of age, the maximal oxidative capacity (Vmax) of GBH dehydrogenase (GHB-D) in the brain reached a rate that was approximately 50% greater than either adult or 18-day fetal values. The Vmax for GBH-oxoacid transhydrogenase (GHB-T) in the brain was negligible at 18 days of gestation but increased 40-fold by 20 days and 100-fold by 70 days after birth. In contrast to the brain, the GHB concentration in the kidney remained at approximately 65% of the adult level from birth to 15 days of age and then rose to adult levels. The activities of both GHB-D and GHB-T were 20% of their adult values in the newborn kidney, and both enzymes increased to near adult activities by 20 days. It appears that GHB-D is the predominant catabolic enzyme for GHB in the fetal and neonatal brain, whereas in the kidney both enzymes participate from the earliest time examined.

Alcohol Oxidoreductases↗