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1.
Nat Commun ; 11(1): 5756, 2020 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-33188210

RESUMEN

In quantizing magnetic fields, graphene superlattices exhibit a complex fractal spectrum often referred to as the Hofstadter butterfly. It can be viewed as a collection of Landau levels that arise from quantization of Brown-Zak minibands recurring at rational (p/q) fractions of the magnetic flux quantum per superlattice unit cell. Here we show that, in graphene-on-boron-nitride superlattices, Brown-Zak fermions can exhibit mobilities above 106 cm2 V-1 s-1 and the mean free path exceeding several micrometers. The exceptional quality of our devices allows us to show that Brown-Zak minibands are 4q times degenerate and all the degeneracies (spin, valley and mini-valley) can be lifted by exchange interactions below 1 K. We also found negative bend resistance at 1/q fractions for electrical probes placed as far as several micrometers apart. The latter observation highlights the fact that Brown-Zak fermions are Bloch quasiparticles propagating in high fields along straight trajectories, just like electrons in zero field.

2.
Clin Obes ; 7(4): 216-221, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28397375

RESUMEN

As childhood obesity increases, it is becoming important to understand the complications of obesity in children and develop novel biomarkers. Evidence indicates that microRNAs (miRNA) are dys-regulated in obesity and may serve as sensitive and specific circulating biomarkers. Non-alcoholic fatty liver disease (NAFLD) is a complication of obesity that ultimately requires a liver biopsy to determine disease severity. While studies have been conducted in adults, no study to date has examined circulating miRNAs in children with obesity and NAFLD. The goal of this study was to evaluate a panel of selected circulating miRNAs in obese children compared to healthy controls. We present here an analysis of a pre-selected panel of 20 candidate miRNAs in obese children compared to healthy controls. The miRNAs were chosen based on having been previously reported to be involved in NAFLD. We found that 16 out of 20 miRNAs tested were elevated at least twofold in children with obesity compared to controls. miR-122 and miR-199a showed the greatest increase in children with obesity versus controls. Both also had a high area under the curve when receiver-operator curves were plotted. Several circulating miRNAs correlated with body mass index (BMI) or serum transaminases. This study provides initial evidence that circulating miRNAs can be measured in the paediatric population and provides several diagnostic candidates increased in children with obesity that may be relevant to NAFLD.


Asunto(s)
MicroARNs/sangre , Obesidad Pediátrica/sangre , Adolescente , Biomarcadores , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Obesidad Pediátrica/complicaciones
3.
Nat Commun ; 8: 14552, 2017 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-28211517

RESUMEN

An energy gap can be opened in the spectrum of graphene reaching values as large as 0.2 eV in the case of bilayers. However, such gaps rarely lead to the highly insulating state expected at low temperatures. This long-standing puzzle is usually explained by charge inhomogeneity. Here we revisit the issue by investigating proximity-induced superconductivity in gapped graphene and comparing normal-state measurements in the Hall bar and Corbino geometries. We find that the supercurrent at the charge neutrality point in gapped graphene propagates along narrow channels near the edges. This observation is corroborated by using the edgeless Corbino geometry in which case resistivity at the neutrality point increases exponentially with increasing the gap, as expected for an ordinary semiconductor. In contrast, resistivity in the Hall bar geometry saturates to values of about a few resistance quanta. We attribute the metallic-like edge conductance to a nontrivial topology of gapped Dirac spectra.

5.
Curr Genet ; 39(1): 49-60, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11318107

RESUMEN

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.


Asunto(s)
Cloroplastos/genética , Euglena gracilis/genética , Transformación Genética , Animales , Chlamydomonas/genética , Clonación Molecular , Euglena gracilis/efectos de los fármacos , Intrones , Modelos Genéticos , Estructura Molecular , Operón , Reacción en Cadena de la Polimerasa , Empalme del ARN , ARN Mensajero/genética , Transgenes
6.
Mol Gen Genet ; 264(5): 682-90, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11212923

RESUMEN

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.


Asunto(s)
Proteínas Algáceas , Cloroplastos/genética , Euglena/genética , Intrones , Operón/genética , Proteínas del Complejo del Centro de Reacción Fotosintética/metabolismo , Complejo de Proteína del Fotosistema II , Proteínas de Plantas/metabolismo , Proteínas Protozoarias , Animales , Secuencia de Bases , Northern Blotting , Clonación Molecular , ADN Complementario/metabolismo , Evolución Molecular , Exones , Genoma , Modelos Genéticos , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Filogenia , ARN Mensajero/metabolismo , ARN de Transferencia/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Homología de Secuencia de Ácido Nucleico
7.
Alcohol ; 22(2): 61-7, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11113619

RESUMEN

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.


Asunto(s)
Alcoholismo/genética , Proteínas Portadoras/genética , Glicoproteínas de Membrana/genética , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso , Polimorfismo Genético , Adulto , Alcoholismo/complicaciones , Alelos , Frecuencia de los Genes , Genotipo , Humanos , Desequilibrio de Ligamiento , Persona de Mediana Edad , Repeticiones de Minisatélite/genética , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Síndrome de Tourette/complicaciones , Síndrome de Tourette/genética
8.
Anesthesiology ; 93(5): 1279-84, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11046217

RESUMEN

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.


Asunto(s)
Encéfalo/metabolismo , Dexametasona/toxicidad , Glucocorticoides/toxicidad , Glucosa/metabolismo , Glucógeno/metabolismo , Hiperglucemia/metabolismo , Hipoglucemiantes/farmacología , Insulina/farmacología , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Encéfalo/efectos de los fármacos , Hiperglucemia/inducido químicamente , Hiperglucemia/tratamiento farmacológico , Masculino , Ratas , Ratas Sprague-Dawley
9.
Mol Psychiatry ; 5(3): 283-92, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10889531

RESUMEN

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.


Asunto(s)
Alcoholismo/genética , Trastorno por Déficit de Atención con Hiperactividad/genética , Proteínas Portadoras/genética , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso , Trastornos Relacionados con Sustancias/genética , Síndrome de Tourette/genética , Adolescente , Secuencia de Bases , Niño , Secuencia Conservada , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Exones , Variación Genética , Humanos , Intrones , Desequilibrio de Ligamiento , Repeticiones de Minisatélite , Polimorfismo Conformacional Retorcido-Simple
11.
Clin Neuropsychol ; 13(4): 450-5, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10806458

RESUMEN

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.


Asunto(s)
Encefalopatías/psicología , Trastornos Mentales/psicología , Práctica Psicológica , Prueba de Secuencia Alfanumérica , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Psicometría , Valores de Referencia , Sensibilidad y Especificidad
12.
Neuropsychol Rev ; 8(1): 11-23, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9585920

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Trastornos del Olfato/etiología , Trastornos de la Percepción/etiología , Olfato/fisiología , Anciano , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/fisiopatología , Demencia/complicaciones , Demencia/fisiopatología , Discriminación en Psicología/fisiología , Evaluación Geriátrica , Humanos , Pruebas Neuropsicológicas , Trastornos del Olfato/fisiopatología , Vías Olfatorias/fisiología , Trastornos de la Percepción/fisiopatología , Umbral Sensorial/fisiología , Índice de Severidad de la Enfermedad
13.
Mol Biol Evol ; 15(1): 76-86, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9491607

RESUMEN

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.


Asunto(s)
ADN de Cloroplastos/genética , ADN Protozoario/genética , Euglénidos/genética , Evolución Molecular , Genes Sobrepuestos , Genes de Plantas/genética , Genes Protozoarios/genética , Intrones/genética , Nucleotidiltransferasas/genética , Proteínas del Complejo del Centro de Reacción Fotosintética/genética , Complejo de Proteína del Fotosistema II , Proteínas de Plantas/genética , Proteínas Protozoarias/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN de Cloroplastos/química , ADN Protozoario/química , Euglénidos/clasificación , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Filogenia , Empalme del ARN , Alineación de Secuencia , Homología de Secuencia de Ácido Nucleico , Especificidad de la Especie
14.
Pediatr Surg Int ; 13(1): 2-5, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9391192

RESUMEN

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.


Asunto(s)
Brotes de Enfermedades , Enterocolitis/microbiología , Yersiniosis/epidemiología , Adolescente , Adulto , Niño , Preescolar , Femenino , Microbiología de Alimentos , Humanos , Lactante , New Hampshire/epidemiología , Vermont/epidemiología , Yersiniosis/diagnóstico
15.
J Med Chem ; 40(5): 766-70, 1997 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-9057863

RESUMEN

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.


Asunto(s)
Antineoplásicos/farmacología , Antivirales/farmacología , Nucleósidos de Purina/farmacología , Pirimidinas/síntesis química , Pirimidinas/farmacología , Ribonucleósidos/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Antivirales/síntesis química , Antivirales/química , División Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Nucleósidos de Purina/síntesis química , Nucleósidos de Purina/química , Pirimidinas/química , Ribonucleósidos/síntesis química , Ribonucleósidos/química , Relación Estructura-Actividad , Células Tumorales Cultivadas
16.
Curr Genet ; 31(1): 89-95, 1997 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9000385

RESUMEN

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.


Asunto(s)
Cloroplastos/genética , Euglena gracilis/genética , Euglena/genética , Intrones , Animales , Mapeo Cromosómico , Clonación Molecular , ADN Complementario/análisis , ADN Complementario/genética , Electroforesis en Gel de Agar , Estructura Molecular , Proteínas del Complejo del Centro de Reacción Fotosintética/genética , Complejo de Proteína del Fotosistema II , Filogenia , Reacción en Cadena de la Polimerasa , Empalme del ARN , ARN Mensajero/genética
17.
Mol Gen Genet ; 257(1): 45-54, 1997 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9439568

RESUMEN

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.


Asunto(s)
Cloroplastos/genética , Euglena/genética , Intrones , Complejo de Proteína del Fotosistema II , Animales , Secuencia de Bases , Secuencia Conservada , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Proteínas del Complejo del Centro de Reacción Fotosintética/genética , Proteínas de Plantas/genética , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico
18.
J Pharm Sci ; 85(5): 461-7, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8742935

RESUMEN

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.


Asunto(s)
Leucotrieno D4/antagonistas & inhibidores , Quinolinas/síntesis química , Tetrazoles/síntesis química , Rastreo Diferencial de Calorimetría , Fenómenos Químicos , Química Física , Estabilidad de Medicamentos , Calefacción , Microscopía , Quinolinas/química , Quinolinas/farmacología , Solubilidad , Tetrazoles/química , Tetrazoles/farmacología , Termodinámica , Difracción de Rayos X
19.
Nucleic Acids Res ; 23(23): 4745-52, 1995 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-8532514

RESUMEN

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.


Asunto(s)
Evolución Biológica , Cloroplastos/genética , ADN de Cloroplastos/genética , ADN Complementario/genética , Euglena/genética , Genes Protozoarios/genética , Intrones/genética , Estructura Secundaria de Proteína , Animales , Secuencia de Bases , ADN de Cloroplastos/química , ADN Complementario/química , Euglena gracilis/química , Euglena gracilis/genética , Datos de Secuencia Molecular , Filogenia
20.
Plant Mol Biol ; 27(5): 1031-5, 1995 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7766872

RESUMEN

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.


Asunto(s)
Chaperoninas/biosíntesis , Chlamydomonas/genética , Chlamydomonas/metabolismo , Regulación de la Expresión Génica de las Plantas , Filogenia , Plastidios/metabolismo , Transcripción Genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Chaperoninas/genética , Calor , Cinética , Mitocondrias/metabolismo , Datos de Secuencia Molecular , Plantas/metabolismo , ARN de Planta/biosíntesis
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