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T A Anderson

Publications and source records attributed to T A Anderson.

At least 19 recordsLinked to original sources
PubMed2006

Evidence that miRNAs are different from other RNAs.

An examination of 513 known pre-miRNAs and 237 other RNAs (tRNA, rRNA, and mRNA) revealed that miRNAs were significantly different from other RNAs (p < 0.001). miRNA genes were less conserved than other RNA genes, although their mature miRNA sequences were highly conserved. The A+U content of pre-miRNAs was higher than non-coding RNA (p < 0.001), but lower than mRNAs. The nucleotides in pre-miRNAs formed more hydrogen bonds and base pairs than in other RNAs. miRNAs had higher negative adjusted minimal folding free energies than other RNAs except tRNAs (p < 0.001). The MFE index (MFEI) was a sufficient criterion to distinguish miRNAs from all coding and non-coding RNAs (p < 0.001). The MFEI for miRNAs was 0.97, significantly higher than tRNAs (0.64), rRNAs (0.59), or mRNAs (0.65). Our findings should facilitate the prediction and identification of new miRNAs using computational and experimental strategies.

Base Pairing↗
PubMed2004

Epitope repertoire of human CD4(+) T cells on the A3 domain of coagulation factor VIII.

Severe hemophilia A patients treated with factor (F)VIII may develop antibodies (Ab) that block FVIII function (inhibitors). Autoimmune inhibitors may develop in subjects without congenital hemophilia, and cause acquired hemophilia. Hemophiliacs without inhibitors and healthy subjects may also have small amounts of antiFVIII Ab. FVIII-specific CD4(+) T cells induce antiFVIII Ab synthesis. Here, we have examined their epitope repertoire in hemophilia patients and healthy subjects. We used overlapping synthetic peptides, spanning the sequence of the FVIII A3 domain, to challenge blood CD4(+) T cells in proliferation assays. The epitopes recognized in hemophilia A patients with or without inhibitors, acquired hemophilia patients, or healthy subjects overlapped, yet had characteristic differences. Most members of one or more study groups recognized the sequence regions 1691-1710, 1801-1820, 1831-1850, and 1941-60. In the proposed three-dimensional structure of the A3 domain, these sequences are largely exposed to the solvent and flanked by flexible sequence loops: these are structural features characteristic of 'universal' CD4(+) T epitopes. Hemophilia A patients with inhibitors recognized prominently only the sequence 1801-1820, which overlaps a known inhibitor binding site. This is consistent with the possibility that CD4(+) T cells recognizing epitopes within residues 1801-1820 have a role in inducing inhibitor synthesis. In contrast, CD4(+) T cells sensitized to sequences 1691-1710 and 1941-60, which are recognized by healthy subjects and hemophilia A patients without inhibitors, might curb inhibitor synthesis.

Antibodies↗
PubMed2003

Human CD4+ T-cell epitope repertoire on the C2 domain of coagulation factor VIII.

Approximately 25% of severe hemophilia A patients develop antibodies (Ab) that neutralize the procoagulant function of factor (F)VIII (inhibitors). Autoimmune FVIII inhibitors may develop in individuals without congenital FVIII deficiency and cause acquired hemophilia. Low titers of anti-FVIII Ab may be present in hemophilia A patients without inhibitors and in healthy blood donors. FVIII-specific CD4+ T-cells drive the synthesis of anti-FVIII Ab. We examined the epitope repertoire of CD4+ T-cells from 15 healthy subjects, 10 hemophilia A patients without inhibitors, 11 hemophilia A patients with inhibitors, and six acquired hemophilia patients. Blood CD4+ T-cells were challenged in proliferation assays with a panel 16 overlapping synthetic peptides, spanning the sequence of the FVIII C2 domain. The sequence region 2291-2330 contained the most frequently and strongly recognized peptides in each of the four subject groups. Crystallographic B factor data and the location of these peptides within the three-dimensional structure of the C2 domain confirm that this region has a high degree of solvent exposure and flexibility within the peptide backbone, which are structural features typical of immunodominant universal CD4+ epitopes. Furthermore, this sequence region overlaps inhibitor-binding sites, suggesting that CD4+ T-cells recognizing peptide sequences within this region might be involved in inhibitor synthesis. The sequence regions 2191-2210 (recognized strongly by each study group except hemophilia A patients with inhibitors) and 2241-2290 (recognized primarily by acquired hemophilia patients and healthy subjects) share the same structural features, and also overlap inhibitor-binding sites. Although similar, there appear to be important differences in the CD4+ epitope repertoires of congenital and acquired hemophilia patients.

Binding Sites↗
PubMed2002

Mercury in Morelet's crocodile eggs from northern Belize.

Recent studies have examined mercury accumulation in crocodilians. However, though most researchers have focused on tissue concentrations, few have examined mercury levels in crocodilian eggs. In July 1995, we analyzed mercury in 31 nonviable Morelet's crocodile ( Crocodylus moreletii) eggs collected from eight nests across three localities in northern Belize. All eggs were found to contain mercury. Based on an individual egg basis, mean concentration of mercury for all three localities was among the lowest reported for any crocodilian species. When localities were examined separately, mean concentrations for Laguna Seca and Gold Button Lagoon were comparable to those observed in other studies, and the mean for Sapote Lagoon was the lowest ever reported. Based on mean nest concentrations, mercury in eggs from Laguna Seca was approximately two- and tenfold higher than for Gold Button Lagoon and Sapote Lagoon, respectively. Variability in mercury concentrations among localities is likely the result of site-specific differences in mercury input, bioavailabilty, and bioaccumulation. Mercury concentrations were relatively uniform in eggs from the same nest and among nests from the same localities. The presence of mercury in Morelet's crocodile eggs suggests exposure in adult females, developing embryos, and neonates. However, crocodiles in these areas show no overt signs of mercury toxicity, and no indication of population decline is evident. A paucity of data on the effects of mercury on crocodilians precludes meaningful speculation as to the biological significance of tissue and egg concentrations. Controlled laboratory studies and long-term population monitoring are needed to address these questions.

Alligators and Crocodiles↗
PubMed2001

Preliminary assessment of perchlorate in ecological receptors at the Longhorn Army Ammunition Plant (LHAAP), Karnack, Texas.

There have been increasing human health and ecological concerns about ionic perchlorate (ClO4-) since it was detected in drinking water sources in 1997. Perchlorate is known to affect thyroid function, causing subsequent hormone disruption and potential perturbations of metabolic activities. According to current estimates, perchlorate is found in the surface of groundwater of 14 states, including Texas. Longhorn Army Ammunition Plant, located in east central Texas, was a facility historically associated with perchlorate-containing propellants and rocket motors. Subsequently, perchlorate contamination in ground and surface waters at the facility has been reported. Soil, sediment, water, vegetation, and animal tissue samples were collected from several locations within the plant for a preliminary site assessment of perchlorate contamination. Perchlorate concentrations ranged from 555-5,557,000 ppb in vegetation, 811-2038 ppb in aquatic insects, below detection limits (ND) to 207 ppb in fish, ND-580 ppb in frogs, and ND-2328 ppb in mammals. Consistent with our hypothesis, aquatic organisms inhabiting perchlorate-contaminated surface water bodies contained detectable concentrations of perchlorate. Additionally, terrestrial organisms were exposed through pathways not necessarily related to contaminated surface waters. Therefore, these data demonstrate that aquatic and terrestrial species are exposed to perchlorate in the environment. To our knowledge, this represents the first incidence of perchlorate exposure among wild animals reported in the scientific literature.

Amphibians↗
PubMed2000

A mechanism of membrane neutral lipid acquisition by the microsomal triglyceride transfer protein.

The microsomal triglyceride transfer protein (MTP) and apolipoprotein B (apoB) belong to the vitellogenin (VTG) family of lipid transfer proteins. MTP is essential for the intracellular assembly and secretion of apoB-containing lipoproteins, the key intravascular lipid transport proteins in vertebrates. We report the predicted three-dimensional structure of the C-terminal lipid binding cavity of MTP, modeled on the crystal structure of the lamprey VTG gene product, lipovitellin. The cavity in MTP resembles those found in the intracellular lipid-binding proteins and bactericidal/permeability-increasing protein. Two conserved helices, designated A and B, at the entrance to the MTP cavity mediate lipid acquisition and binding. Helix A (amino acids 725-736) interacts with membranes in a manner similar to viral fusion peptides. Mutation of helix A blocks the interaction of MTP with phospholipid vesicles containing triglyceride and impairs triglyceride binding. Mutations of helix B (amino acids 781-786) and of N780Y, which causes abetalipoproteinemia, have no impact on the interaction of MTP with phospholipid vesicles but impair triglyceride binding. We propose that insertion of helix A into lipid membranes is necessary for the acquisition of neutral lipids and that helix B is required for their transfer to the lipid binding cavity of MTP.

Amino Acid Sequence↗
PubMed2000

Organochlorine contaminants in Morelet's crocodile (Crocodylus moreletii) eggs from Belize.

Non-viable eggs of Morelet's crocodile (Crocodylus moreletii) were collected from Gold Button (GBL) and New River lagoons (NRL) in northern Belize and screened for organochlorine (OC) compounds using gas chromatography (GC) with electron capture detection (ECD). All egg samples from both lagoons (n = 24) tested positive for one or more OCs. Primary contaminants were p,p-DDE and methoxychlor, detected in 100% and 29% of the eggs examined, respectively. Concentrations of individual OC contaminants ranged from 1 ppb (ng chemical/g egg) to > 0.5 ppm (microgram chemical/g egg). Total concentrations of OCs (sum of all OCs) for one egg collected from a nest at GBL reached as high as 0.7 ppm. Sediment samples from both lagoons also tested positive for OCs (lindane, aldrin, methoxychlor, heptachlor epoxide, p,p-DDT, among others). Nest media (soil and plant material) collected from crocodile nests at GBL were positive for p,p-DDT, methoxychlor, aldrin, endosulfan II, and endrin aldehyde. Based on the 24 egg samples analyzed to date, crocodiles from both lagoons are being exposed to OCs. Such exposure may present a health threat to populations of crocodiles in Central America.

Aldrin↗
PubMed2000

DDE in eggs of two crocodile species from Belize.

Organochlorine (OC) residues were recently detected in nonviable Morelet's crocodile (Crocodylus moreletii) eggs from northern Belize. To further the assessment of contaminant exposure in Belizean crocodiles, nonviable Morelet's crocodile eggs (n = 11) from southern Belize and American crocodile (Crocodylus acutus) eggs (n = 12) from the coastal zones of Belize were screened for 20 OCs. Results indicated p,p-DDE to be the most prevalent OC (96% occurrence) in eggs examined, with concentrations ranging from 5 to 372 ng/g. These concentrations are similar to those observed in crocodile eggs (10-180 ng/g) from northern Belize. A general trend toward higher DDE concentrations in Morelet's crocodile eggs (mean = 103 ppb) compared with American crocodile eggs (mean = 31 ppb) was observed. However, this trend may be due to site-specific contamination rather than differences in interspecific susceptibility to chemical exposure. Other OCs detected in crocodile eggs included the parent compound, p,p-DDT, and its metabolite, p, p-DDD.

Alligators and Crocodiles↗
PubMed2000

Degradation of atrazine, metolachlor, and pendimethalin in pesticide-contaminated soils: effects of aged residues on soil respiration and plant survival.

This study was conducted to determine the effects of pesticide mixtures on degradation patterns of parent compounds as well as effects on soil microbial respiration. Bioavailability of residues to sensitive plant species was also determined. Soil for this study was obtained from a pesticide-contaminated area within an agrochemical dealer site. Degradation patterns were not affected by the presence or absence of other herbicides in this study. Atrazine concentrations were significantly lower at 21 through 160 days aging time compared to day 0 concentrations. Metolachlor and pendimethalin concentrations were not significantly different over time and remained high throughout the study. Microbial respiration was suppressed in treated soils from day 21 to day 160. Soybean and canola were the most successful plant species in the germination and survival tests. Generally, with increased aging of pesticides in soil, germination time decreased. Survival time of plants increased over time for some treatments indicating possible decreased bioavailability of pesticide residues. In some cases, survival time decreased at the longer 160-day aging period, possibly indicating a change in bioavailability, perhaps as the result of formation of more bioavailable and phytotoxic metabolites. No interactive effects were noted for mixtures of pesticides compared to individually applied pesticides in terms of degradation of the parent compound or on seed germination, plant survival, or microbial respiration.

Acetamides↗
PubMed1999

A common binding site on the microsomal triglyceride transfer protein for apolipoprotein B and protein disulfide isomerase.

The assembly of triglyceride-rich lipoproteins requires the formation in the endoplasmic reticulum of a complex between apolipoprotein B (apoB), a microsomal triglyceride transfer protein (MTP), and protein disulfide isomerase (PDI). In the MTP complex, the amino-terminal region of MTP (residues 22-303) interacts with the amino-terminal region of apoB (residues 1-264). Here, we report the identification and characterization of a site on apoB between residues 512 and 721, which interacts with residues 517-603 of MTP. PDI binds in close proximity to this apoB binding site on MTP. The proximity of these binding sites on MTP for PDI and amino acids 512-721 of apoB was evident from studies carried out in a yeast two-hybrid system and by co-immunoprecipitation. The expression of PDI with MTP and apoB16 (residues 1-721) in the baculovirus expression system reduced the amount of MTP co-immunoprecipitated with apoB by 73%. The interaction of residues 512-721 of apoB with MTP facilitates lipoprotein production. Mutations of apoB that markedly reduced this interaction also reduced the level of apoB-containing lipoprotein secretion.

Amino Acid Sequence↗
PubMed1999

The structure of vitellogenin provides a molecular model for the assembly and secretion of atherogenic lipoproteins.

The assembly of atherogenic lipoproteins requires the formation in the endoplasmic reticulum of a complex between apolipoprotein (apo)B, a microsomal triglyceride transfer protein (MTP) and protein disulphide isomerase (PDI). Here we show by molecular modelling and mutagenesis that the globular amino-terminal regions of apoB and MTP are closely related in structure to the ancient egg yolk storage protein, vitellogenin (VTG). In the MTP complex, conserved structural motifs that form the reciprocal homodimerization interfaces in VTG are re-utilized by MTP to form a stable heterodimer with PDI, which anchors MTP at the site of apoB translocation, and to associate with apoB and initiate lipid transfer. The structural and functional evolution of the VTGs provides a unifying scheme for the invertebrate origins of the major vertebrate lipid transport system.

Amino Acid Sequence↗
PubMed1998

The structural basis of lipid interactions in lipovitellin, a soluble lipoprotein.

BACKGROUND: The conformation and assembly of lipoproteins, protein containing large amounts of noncovalently bound lipid, is poorly understood. Lipoproteins present an unusual challenge as they often contain varying loads of lipid and are not readily crystallized. Lipovitellin is a large crystallizable oocyte protein of approximately 1300 residues that contains about 16% w/w lipid. Lipovitellin contains two large domains that appear to be conserved in both microsomal triglyceride transfer protein and apolipoprotein B-100. To gain insight into the conformation of a lipoprotein and the potential modes of binding of both neutral and phospholipid, the crystal structure of lamprey lipovitellin has been determined. RESULTS: We report here the refined crystal structure of lipovitellin at 2.8 A resolution. The structure contains 1129 amino acid residues located on five peptide chains, one 40-atom phosphatidylcholine, and one 13-atom hydrocarbon chain. The protein contains a funnel-shaped cavity formed primarily by two beta sheets and lined predominantly by hydrophobic residues. CONCLUSIONS: Using the crystal structure as a template, a model for the bound lipid is proposed. The lipid-binding cavity is formed primarily by a single-thickness beta-sheet structure which is stabilized by bound lipid. This cavity appears to be flexible, allowing lipid to be loaded or unloaded.

Amino Acid Sequence↗
PubMed1998

Tumorigenicity of sodium ascorbate in male rats.

Sodium ascorbate, like other sodium salts such as saccharin, glutamate, and bicarbonate, produces urinary alterations when fed at high doses to rats, which results in mild superficial urothelial cytotoxicity and regeneration but not tumors in a standard 2-year bioassay. Sodium saccharin was shown to produce a low incidence of bladder tumors in rats if administered in a two-generation bioassay. In the present study, we evaluated sodium ascorbate in a two-generation bioassay that involved feeding to the male and female parental F344 rats for 4 weeks before mating, feeding the dams during gestation and lactation, and then feeding the weaned (at 28 days of age) male F1 generation rats for the remainder of their lifetime (up to 128 weeks of the experiment). Dietary levels of 1.0, 5.0, and 7.0% sodium ascorbate were tested. At 5.0 and 7.0% sodium ascorbate, there was an increase in urinary bladder urothelial papillary and nodular hyperplasia and the induction of a few papillomas and carcinomas. There was a dose-responsive increase in renal pelvic calcification and hyperplasia and inhibition of the aging nephropathy of rats even at the level of 1% sodium ascorbate. Because the short-term urothelial effects of sodium ascorbate in rats are inhibited by treatments producing urinary acidification to pH < 6.0, we coadministered high doses of long-term NH4Cl to groups of rats with 5.0 or 7.0% sodium ascorbate to evaluate the long-term effects. The combination of 7.0% sodium ascorbate plus 2.78% NH4Cl in the diet was toxic, and the group was terminated early during the course of the experiment. The group fed 5.0% sodium ascorbate plus 2.04% NH4Cl showed complete inhibition of the urothelial effects of sodium ascorbate and significant inhibition of its renal effects. We also demonstrated the presence of a calcium phosphate-containing urinary precipitate in rats fed sodium ascorbate at all doses, in a dose-responsive manner. The formation of the precipitate was inhibited by coadministration with NH4Cl. The proliferative effects of sodium ascorbate on the male rat urinary tract in this study are similar to those seen with sodium saccharin when administered in a two-generation bioassay. Mechanistic information suggests that this is a high-dose, rat-specific phenomenon.

Ammonium Chloride↗
PubMed1997

Enhanced degradation of deethylatrazine in an atrazine-history soil of Iowa.

The degradation of deethylatrazine (DEA), a major metabolite of atrazine, was studied by using radiotracers in soils with two different atrazine histories. DEA degradation was enhanced in soils which had received long-term exposure to atrazine (atrazine-history soil) compared with soils that had not received long-term atrazine exposure (no-history soil). After 60 days of incubation, mineralization of DEA to 14CO2 in the atrazine-history surface soil was twice that in the no-history surface soils, with 34% and 17% of the applied 14C-DEA as CO2, respectively. In surface soils, 25% of the applied 14C remained as DEA in the atrazine-history soil, compared with 35% in the no-history soil. Microbial plate counts indicated an increase in numbers of bacteria and fungi in soils incubated with DEA compared to control soils. No significant difference in total microbial respiration was seen among atrazine-history and no-history soils incubated with DEA, but DEA-treated soils had greater microbial respiration than untreated control soils after 6 days. A 14C-most-probable-number procedure was used to enumerate specific DEA degraders. A greater number of DEA degraders were indicated in atrazine-history subsurface soil compared with all other soils in this study (p < 0.05). From this study, it appears that an increase in microbial activity contributes to decreased persistence and increased degradation of DEA in soils that have had long-term exposure to atrazine at field application rates, compared to soils with no long-term exposure. Decreased persistence of this major metabolite of atrazine in atrazine-history soils is important in that there will be less available for movement in surface runoffs.

Atrazine↗
PubMed1997

Nutritional regulation of insulin-like growth factor-I mRNA expression in barramundi, Lates calcarifer.

The effect of nutritional status on IGF-I mRNA expression in the liver and brain of juvenile barramundi (Lates calcarifer) was investigated. Fish were either fed a satiety ration (SAT) or starved (STV) for 6 weeks. Starved fish demonstrated significantly lower condition factor and hepatic IGF-I mRNA expression at 3 and 6 weeks, when compared with the SAT group. IGF-I mRNA expression in the brain was 10 fold lower than the liver and was not affected by ration size. These results suggest the liver is the major site of IGF-I mRNA synthesis and hepatic but not brain IGF-I mRNA expression is regulated by food availability in juvenile barramundi.

Animals↗