Early childhood educational intervention and long-term developmental outcomes.
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Adolescent↗
Biomedical subjects
M D Thompson
Publications and source records attributed to M D Thompson.
Chloroplast transformation in Euglena gracilis: splicing of a group III twintron transcribed from a transgenic psbK operon.
The Escherichia coli aadA gene product, which confers resistance to spectinomycin and streptomycin, has been widely used as a dominant selectable marker for chloroplast transformation of Chlamydomonas and tobacco. An aadA transformation cassette was adapted for expression in Euglena gracilis chloroplasts by replacing the Chlamydomonas promoter and 3' untranslated region (UTR) with the E. gracilis psbA promoter and 3' UTR. Transgenic DNA was introduced into E. gracilis chloroplasts by biolistic transformation. Streptomycin- and spectinomycin-resistant colonies were obtained, which screened positively for the presence of the transforming vector by PCR amplification. Although integration of the transforming DNA into the chloroplast genome was not detected, transforming DNA was stably maintained in the chloroplast as an episomal element during continuous selection on antibiotics. The aadA cassette was also inserted into a transformation vector which contained the independently expressed psbK operon from either E. gracilis or a closely related species, E. stellata. The psbK operon contained at least two group III introns and a group III twintron, was highly expressed, and was only 1.5 kb in length. In transgenic E. gracilis chloroplasts, a truncated E. stellata psbK operon was transcribed, and the resultant pre-mRNA was accurately spliced. This system should allow the first direct analysis of group II and group III intron-splicing mechanisms. In addition, it could prove useful in the study of many other Euglena transcription and processing events.
Animals↗
Comparison of psbK operon organization and group III intron content in chloroplast genomes of 12 Euglenoid species.
A novel mixed operon has been identified in the photosynthetic protist E. gracilis. The genes for psbK, ycf12, psaM, and trnR are co-transcribed. The resulting tetracistronic transcripts are processed through endonucleolytic cleavage of the intergenic spacers and intron splicing to form three mature monocistronic mRNAs and a tRNA. A group III twintron and a group III intron are located in psbK. Another group III intron is found in ycf12. The psbK operon has been cloned by PCR amplification from nine related Euglenoid species. In each species, the gene order and content of the psbK operon is conserved. The psbK operons contain phylogenetically conserved eubacterial promoter, translational, and 3' processing elements. Intron content varies significantly from species to species. Based on a comparison of the intron content with the results of phylogenetic analysis, group III intron evolution within the Euglenoid lineage is much more complex than previously believed.
Algal Proteins↗
Serotonin transporter gene polymorphisms in alcohol dependence.
The serotonin transporter (5-HTT) gene is a candidate gene in alcohol dependence because serotonin reuptake inhibitors (SRIs) can alleviate alcohol withdrawal. Studies of the 5-HTT gene in alcohol dependence have not resulted in a consensus. Recent studies have examined the transcriptionally active promoter polymorphism, a 44-bp deletion resulting in short (S) or long (L) alleles. In this study, 131 alcohol-dependent patients of Northern and Western European descent were genotyped. Seventy of these patients were diagnosed with alcohol dependence without comorbid disorders. Sixty-one patients were diagnosed with alcohol dependence comorbid with Tourette syndrome (alcoholic-TS). We found an excess of the S allele in alcohol-dependent patients (47%) compared with 125 ethnically matched controls (39%). A similar trend was found in 150 ethnically matched TS patients without alcohol dependence comorbidity (51%). However, the statistical significance of this trend in the data was not present after Bonferroni correction. The data presented suggests a trend toward increased frequency of the S promoter allele in alcohol-dependent, alcoholic-TS and TS patients.
Adult↗
Human dopamine transporter gene: coding region conservation among normal, Tourette's disorder, alcohol dependence and attention-deficit hyperactivity disorder populations.
The dopamine transporter (DAT) provides major regulation of the synaptic levels of dopamine and is a principal target of psychostimulant drugs. Associations between DAT gene polymorphisms and human disorders with possible links to dopaminergic neurotransmission, including attention-deficit/hyperactivity disorder (ADHD) and consequences of cocaine and alcohol administration, have been reported. We now report approximately 60000 bp of genomic sequence containing the entire DAT gene. This sequence was used to amplify each of the 15 DAT gene exons and several introns and analyze these amplification products by single-stranded sequence conformation (SSCP) and/or direct sequencing. These results define silent allelic single nucleotide sequence variants in DAT gene exons 2, 6, 9 and 15. Rare conservative mutations are identified in amino acids encoded by DAT exons 2 and 8. Analyses of the common nucleotide variants and the previously reported VNTR in the non-coding region of exon 15 define the pattern of linkage disequilibrium across the DAT locus. These comprehensive analyses, however, fail to identify any common protein coding DAT sequence variant in more than 150 unrelated individuals free of neuropsychiatric disease, 109 individuals meeting City of Hope criteria for Tourette's syndrome, 64 individuals with DSM-IV diagnoses of ethanol dependence, or 15 individuals with ADHD. These data are consistent with substantial evolutionary conservation of the DAT protein sequence. They suggest that gene variants that alter levels of DAT expression provide the best current candidate mechanism for reported associations between DAT gene markers, ADHD and other more tentatively associated neuropsychiatric disorders.
Adolescent↗
The effect of chronic dexamethasone-induced hyperglycemia and its acute treatment with insulin on brain glucose and glycogen concentrations in rats.
BACKGROUND: In the rat model of forebrain ischemia, long-term dexamethasone treatment is reported to cause hyperglycemia and worsen postischemic functional and histologic injury. This effect was assumed to result from glucose enhancement of intraischemic lactic acidosis within the brain. Short-term insulin therapy restored normoglycemia but did not return histologic injury completely to baseline values. Using a nonischemic rat model, the current study attempted to identify a metabolic basis for such outcome data. METHODS: Fifty-eight halothane-anesthetized (1.3% inspired) Sprague-Dawley rats were assigned randomly to be administered either no treatment (N = 18) or 2 mg/kg intraperitoneal dexamethasone (N = 40). The latter were administered dexamethasone 3 h before the study only (N = 8) or for 3 h before the study plus daily for 1 day (N = 8), 2 days (N = 8), or 4 days (N = 16). Of the rats treated with dexamethasone for 4 days, one half (N = 8) were administered an insulin-containing saline infusion subsequently to restore normoglycemia short-term. All other rats (N = 50) were administered an infusion of saline without insulin. Plasma glucose was quantified, and brains were excised after in situ freezing. Brain glucose and glycogen concentrations were measured using enzymatic fluorometric analyses. RESULTS: After 4 days of dexamethasone treatment, plasma glucose was 159% greater than in rats administered placebo (i.e., 22.01 +/- 4.66 vs. 8.51 +/- 1.65 micromol/ml; mean +/- SD; P < 0.0001). Brain glucose concentrations increased parallel to plasma glucose. An insulin infusion for 27 +/- 5 min restored normoglycemia but resulted in a brain-to-plasma glucose ratio that was 32% greater than baseline values (P < 0.01). Neither dexamethasone nor the combination of dexamethasone plus insulin affected brain glycogen concentrations. CONCLUSIONS: In a nonischemic rat model, dexamethasone alone had no independent effect on the brain-to-plasma glucose ratio. However, short-term insulin therapy caused a dysequilibrium between plasma and brain glucose, resulting in an underestimation of brain glucose concentrations when normoglycemia was restored. The dysequilibrium likely was caused by the rapid rate of glucose reduction. The magnitude of the effect may account for the failure of insulin to reverse dexamethasone enhancement of neurologic injury completely in a previous report that used the rat model of forebrain ischemia.
Animals↗
Clinical utility of the Trail Making Test practice time.
The Trail Making Test (TMT) is one of the most frequently used measures in clinical neuropsychology. Data obtained from the TMT practice times were analyzed to determine their utility in predicting success and failure on the full version of the test and to allow establishment of criteria by which to judge administration or discontinuation of the full test. Results indicated that TMT practice times were useful in predicting successful completion of Part A and B of the TMT. Tables are provided which describe the classification accuracy of various TMT practice times. These tables allow clinicians to select a practice-time cutoff and then use the cutoff as a heuristic to assist in the decision to administer the remainder of that particular part of the TMT or discontinue the test. A 20-s cutoff resulted in optimal prediction of successful completion (< 180 s) of TMT Part A. A cutoff of 30 s optimally predicted successful completion (< 300 s) of TMT Part B.
Adult↗
Epidural blockade for labor and cesarean section with associated L4-5 lipomyelocele.
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Adult↗
Surgical aspects of an outbreak of Yersinia enterocolitis.
Eleven patients with Yersinia enterocolitica infections were identified in the Upper Valley of New Hampshire and Vermont during October and November of 1995. Three children presented with an appendicitis-like picture. Two underwent appendectomy, one of whom was the outbreak's index case. Both appendectomy patients presented with lower abdominal pain, fever, vomiting, and a right lower quadrant mass associated with leukocytosis. Both had terminal ileitis, and in both, cultures of peritoneal fluid and a mesenteric lymph node grew Y. enterocolitica. Even during an outbreak there is no consistently reliable nonoperative way to separate a sporadic case of appendicitis from one whose appendicitis-like symptoms are due to Yersinia. In addition, a small percentage of Yersinia patients will present with true appendicitis as a complication of their disease.
Adolescent↗
Olfaction in persons with Alzheimer's disease.
The need for low cost, noninvasive procedures for aiding in the diagnosis and understanding of Alzheimer's Disease (AD) has led to theories and procedures examining the role of olfactory disorders because of the finding that the brains of AD patients invariably exhibit neuropathology in the hippocampus and entorhinal cortex. This loss correlates with the increase in the number of plaques and tangles and with the severity of dementia. Considered together, these findings suggest that brain structures closely related to the olfactory system demonstrate significant histopathology in AD. A comprehensive review of the literature pertaining to olfaction in persons with AD revealed that the olfactory identification ability of patients with memory disorders is impaired relative to controls. Consistency is lacking, however, when olfactory detection thresholds are investigated. Also, there is inconsistency in regards to severity of illness and olfactory function. In addition to differentiating AD patients from normals, the olfactory paradigm has shown some limited usefulness in differentiating AD patients from some other demented patients.
Aged↗
A maturase-encoding group III twintron is conserved in deeply rooted euglenoid species: are group III introns the chicken or the egg?
The fourth intron of the Euglena gracilis chloroplast photosystem II gene, psbCi4, is a 1,605-bp twintron composed of two group III introns and a coding locus for a 458-aa polypeptide, mat1, located in the internal intron. psbCi4 homologs have been identified in seven euglenoids, including E. myxocylindracea, E. viridis, E. deses, E. pisciformis, Cryptoglena pigra, Eutreptia sp., and Lepocinclis beutschlii. All of the species examined contain both the group III twintron and the mat1 locus, revealing a more widespread occurrence of group III introns than previously known. The L. beutschlii mat1 locus is interrupted by two novel mini-group II introns of 224 and 258 nt, the smallest group II introns yet identified. Reverse transcriptase polymerase chain reaction analysis confirmed the splicing boundaries of the external and internal E. myxocylindracea, E. viridis, and E. deses introns as well as the novel L. beutschlii mat1 introns. As determined by comparative phylogenetic analysis, group III introns contain a structural homolog of group II intron domain VI. The mat1 loci encode peptide motifs characteristic of group II intron maturases. A group III intron-encoded protein whose predicted sequence is similar to group II intron-encoded maturases and a bona fide domain VI within group III introns are compelling evidence for a common ancestor of group II and group III introns.
Amino Acid Sequence↗
Synthesis and evaluation of 6-(dibromomethyl)-5-nitropyrimidines as potential antitumor agents.
A series of 2,4,6-trisubstituted-5-nitropyrimidines have been prepared and evaluated for inhibition of proliferation of L1210 and H.Ep.2 cells in vitro. The most potent compound was 6-(dibromomethyl)-2-methoxy-4-morpholino-5-nitropyrimidine (11) (L1210, IC50 = 0.32 microM; H.Ep.2, IC50 = 1.6 microM). Of the 6-substituents incorporated, only CHBr2, CH2Br, and CHO were compatible with antiproliferative activity, while a wider variety of 4-substituents were tolerated. At concentrations near the IC50 for antiproliferative activity, a delayed resumption of cell proliferation in L1210 cultures indicated that the activity of the compounds was short-lived and suggested they might act by an alkylation mechanism.
Animals↗
Two new group-II twintrons in the Euglena gracilis chloroplast are absent in basally branching Euglena species.
Studies of the phylogeny and chloroplast intron content of selected Euglena species have led to insights in our understanding of the timing of intron acquisition. In the current study, two new twintrons, found in E. gracilis, have been characterized by the analysis of partially spliced pre-mRNAs. Intron 1 of atpE is a 463-nt group-II intron interrupted by a second group-II intron 320 nt long. Intron 1 of psbD is also a group-II twintron with external and internal introns of 635 nt and 463 nt, respectively. The two introns composing the psbD twintron, as well as six additional group-II introns found in the E. gracilispsbD gene, are not present in several basally branching Euglena species, including E. myxocylindracea, E. stellata and E. viridis. The distribution of psbD introns in Euglena is consistent with a late evolutionary acquisition of group-II introns in this lineage.
Animals↗
Extensive structural conservation exists among several homologs of two Euglena chloroplast group II introns.
82 of the 155 chloroplast introns in Euglena gracilis have been categorized as group II introns. Because they are shorter and more divergent than group II introns from other organisms, the assignment of these Euglena introns to the group II class has been questioned. In the current study, two homologs of E. gracilis petB intron 1 and four homologs of psbC intron 2 have been isolated from related species and characterized. Based on a comparative sequence analysis of intron homologs, the intron core and four of the six helical domains present in the canonical group II intron structural model are conserved in E. gracilis petB intron 1 and psbC intron 2 and all of their homologs. Distal portions of domain I, which are involved in most of the tertiary interactions, are less well conserved than the central core.
Animals↗
Preparation and characterization of polymorphs for an LTD4 antagonist, RG 12525.
This report describes the preparation and characterization of two polymorphic forms of RG 12525, a leukotriene D4 (LTD4) antagonist. Polymorph I is prepared by recrystallization from methanol or titration of the sodium salt of RG 12525 with citric acid. Polymorph II is prepared by recrystallization from methanol or titration of the ammonium salt of RG 12525 with citric acid. The polymorphic system is enantiotropic, with pure form I melting at 154 degrees C, 3 deg less than the melting temperature of form II. Form I is thermodynamically more stable than form II at room temperature. These polymorphic forms are differentiated using microscopy, differential scanning calorimetry (DSC), infrared spectroscopy (IR), and powder X-ray diffraction (XRD) analysis. Solubility properties from 31 to 72 degrees C were determined to be similar for both forms. The calculated solubilities at 25 degrees C are 7.6 and 9.8 microM for forms I and II, respectively. The free energy change from form II to form I at 25 degrees C is -0.15 kcal/mol. Thermodynamic properties of the system are summarized using a schematic free energy diagram.
Calorimetry, Differential Scanning↗
Evidence for the late origin of introns in chloroplast genes from an evolutionary analysis of the genus Euglena.
The origin of present day introns is a subject of spirited debate. Any intron evolution theory must account for not only nuclear spliceosomal introns but also their antecedents. The evolution of group II introns is fundamental to this debate, since group II introns are the proposed progenitors of nuclear spliceosomal introns and are found in ancient genes from modern organisms. We have studied the evolution of chloroplast introns and twintrons (introns within introns) in the genus Euglena. Our hypothesis is that Euglena chloroplast introns arose late in the evolution of this lineage and that twintrons were formed by the insertion of one or more introns into existing introns. In the present study we find that 22 out of 26 introns surveyed in six different photosynthesis-related genes from the plastid DNA of Euglena gracilis are not present in one or more basally branching Euglena spp. These results are supportive of a late origin for Euglena chloroplast group II introns. The psbT gene in Euglena viridis, a basally branching Euglena species, contains a single intron in the identical position to a psbT twintron from E.gracilis, a derived species. The E.viridis intron, when compared with 99 other Euglena group II introns, is most similar to the external intron of the E.gracilis psbT twintron. Based on these data, the addition of introns to the ancestral psbT intron in the common ancester of E.viridis and E.gracilis gave rise to the psbT twintron in E.gracilis.
Animals↗
Chlamydomonas transcripts encoding three divergent plastid chaperonins are heat-inducible.
Three cDNAs encoding plastid cpn60 chaperonin subunits have been isolated from the unicellular green alga Chlamydomonas reinhardtii. Based on comparisons of the predicted amino acid sequences, we conclude that Chlamydomonas, like higher plants, contains divergent plastid cpn60-alpha and cpn60-beta subunits. The predicted amino acid sequences of the two Chlamydomonas cpn60-beta subunits differ significantly (24% divergent), indicating that the two cpn60-beta subunits have been selectively maintained for a considerable period of time. Unlike plastid chaperonin transcripts in higher plants, heat shock conditions (42 degrees C) lead to a rapid increase (10- to 30-fold) in the level of each of the three plastid transcripts.
Amino Acid Sequence↗
Characterization of rps17, rp19 and rpl15: three nucleus-encoded plastid ribosomal protein genes.
Approximately two-thirds of the 55 to 60 plastid ribosomal proteins are encoded in the nucleus. Since the protein products of each of these genes are needed in equal amounts for ribosome assembly, their expression may be coordinately regulated by common mechanisms. To begin to understand how the expression of these genes is regulated, we have isolated cDNA and genomic clones for three plastid ribosomal protein genes from an Arabidopsis thaliana library. The genes rps17, rpl9 and rpl15, encoding plastid ribosomal proteins CS17, CL9 and CL15, respectively, are located in the nuclear genome and Southern blot data suggest that each is a single copy gene in A. thaliana. Northern blot data show that transcripts from rps17, rpl9 and rpl15 are much more abundant in leaves and stems than they are in roots. The nucleotide sequences of each of these three genes were determined and their transcriptional initiation sites identified. rps17 transcripts have multiple 5' ends suggesting that they are initiated at multiple sites or are post-transcriptionally processed at their 5' end. rpl9 and rpl15 apparently have unique transcriptional initiation sites but are post-transcriptionally processed to remove six and three introns, respectively, from their primary transcripts. We have examined the genomic sequences for motifs that may be important for the proper expression of these genes. A 7 bp sequence motif, whose consensus is 5'-AGGCCCA-3', flanked by AT-rich regions was identified between 38 and 73 nucleotides upstream of the rps17, rpl9 and rpl15 transcriptional initiation sites.
Amino Acid Sequence↗