RESUMEN
Delimiting species can be challenging, but is a key step for the critical examination of evolutionary history and for prioritizing conservation efforts. Because systematic relationships are often determined iteratively using tests based on taxonomy, such methods can fail to detect cryptic variation and result in biased conclusions. Conversely, discovery-based approaches provide a powerful way to define operational taxonomic units and test species boundaries. We compare both approaches (taxonomy-based delimitation - TBD and discovery-based delimitation - DBD) within North American jumping mice (Zapodinae) using broad sampling, multilocus analyses, and ecological tests. This group diversified through the dynamic glacial-interglacial periods of the Quaternary and phylogeographic tests reveal 28 lineages that correspond poorly with current taxonomy (4 species, 32 nominal subspecies). However, neither the 4-species or 28-lineage hypotheses are optimal for species-level classification. Rather, information theoretic approaches (Bayes Factors) indicate a 15-species hypothesis is best for characterizing genetic variation in this group, with subsequent iterative pairwise ecological tests failing to confirm four species pairs. Taken together, evolutionary and ecological tests capture divergence among 11 putative species that, if upheld by additional tests, will lead to taxonomic revision and reevaluation of conservation plans.
Asunto(s)
Roedores/clasificación , Animales , Apolipoproteínas B/clasificación , Apolipoproteínas B/genética , Proteína BRCA1/clasificación , Proteína BRCA1/genética , Teorema de Bayes , Citocromos b/clasificación , Citocromos b/genética , Variación Genética , Filogenia , Filogeografía , Roedores/genética , Especificidad de la Especie , Estados UnidosRESUMEN
OBJECTIVE: Young women with T1D develop CHD without any apparent lipid related risk factor. To determine whether abnormalities in the five immunochemically defined apoB-containing lipoprotein subclasses might influence this risk, we have measured these subclasses in T1D subjects. RESEARCH DESIGN AND METHODS: ApoA- and B-containing lipoprotein subclasses were isolated immunochemically and quantitated in 37 young (mean age 31.8+/-12.7 years) otherwise healthy subjects (16 males; 21 females) with T1D (HbA1c=8.2+/-1.7%) treated conventionally with subcutaneous insulin. RESULTS: T1D women had significantly more cholesterol-rich Lp-B particles (T1D: 55.9+/-4.5 vs. control 46.8+/-11.1mg apoB/dL; p<.01) which were over-represented in the apolipoprotein B particle pool (apoB/Lp-B: T1D: 1.49+/-.19 vs. control: 1.67+/-.22; p<.01). HbA1c correlated with Lp-B (r=0.60; p<.001) and the mass of apoB subclasses containing apoC-III (r=0.69; p<.001). CONCLUSIONS: Women with T1D have a disturbance in the transport of Lp-B particles manifested by both an absolute and relative increase in their number that may result from portal hypoinsulinemia and reduced LDL B,E receptor activity. This pathway may enhance CHD risk in T1D women when of LDL and apoB levels are normal.
Asunto(s)
Apolipoproteínas B/sangre , Diabetes Mellitus Tipo 1/sangre , Adolescente , Adulto , Apolipoproteína C-III/sangre , Apolipoproteínas B/clasificación , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Femenino , Hemoglobina Glucada/metabolismo , Índice Glucémico , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Valores de Referencia , Adulto JovenRESUMEN
According to the concept of apolipoprotein (apo)-defined lipoproteins, apoA-I-containing lipoproteins consist of two subclasses referred to as lipoprotein A-I (LpA-I) and lipoprotein A-I:A-II (LpA-I:A-II), and apoB-containing lipoproteins of five subclasses, namely lipoprotein B (LpB), lipoprotein B:C (LpB:C), lipoprotein B:E (LpB:E), lipoprotein B:C:E (LpB:C:E), and lipoprotein A-II:B:C:D:E (LpA-II:B:C:D:E). The purpose of this study was to determine the levels of apoA-I- and apoB-containing lipoprotein subclasses before and after fluvastatin treatment of patients with chronic renal insufficiency. ApoA-I- and apoB-containing lipoprotein subclasses were measured in 15 patients with chronic renal failure and 15 asymptomatic subjects. The effect of fluvastatin on lipoprotein subclasses was determined in a randomized, double-blind, placebo-controlled, two-way, treatment period crossover study. Patients were administered fluvastatin 40 mg/day or placebo during 8 weeks in a randomized order. Patients were characterized by significantly higher levels of LpB (P < 0.001), LpB:C (P < 0.001), and LpB:E (P < 0.05), and slightly higher levels of LpB:C:E and LpA-II:B:C:D:E than controls. The levels of LpA-I:A-II were significantly lower (P < 0.01) in patients than controls. Fluvastatin treatment reduced all apoB-containing subclasses, but only the reduced level of LpB subclass was statistically significant (P < 0.02). The levels of LpA-I and LpA-I:A-II were not affected. Fluvastatin treatment reduced and normalized LpB and LpB:E subclasses. Although slightly reduced, the levels of markedly atherogenic LpB:C subclass were not normalized. The potential role of LpB:C on the progression of coronary artery disease in chronic renal insufficiency remains to be determined in future studies.
Asunto(s)
Apolipoproteínas B/efectos de los fármacos , Ácidos Grasos Monoinsaturados/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Indoles/uso terapéutico , Fallo Renal Crónico/tratamiento farmacológico , Anciano , Apolipoproteínas B/sangre , Apolipoproteínas B/clasificación , Estatura , Índice de Masa Corporal , Estudios de Cohortes , Estudios Cruzados , Método Doble Ciego , Ácidos Grasos Monoinsaturados/administración & dosificación , Femenino , Fluvastatina , Tasa de Filtración Glomerular , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Indoles/administración & dosificación , Fallo Renal Crónico/sangre , Lipoproteínas/sangre , Lipoproteínas/clasificación , Lipoproteínas/efectos de los fármacos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the contribution of albumin synthetic and catabolic rates to steady state levels in a patient with idiopathic hypoalbuminemia. METHODS: Using L-[1-(13)C] valine, both FSR (fractional synthesis rate) as well as FCR (fractional catabolic rate) were studied. Human albumin cDNA analysis and determination of the exact albumin mass by electrospray mass spectrometry were performed. RESULTS: Compared with controls, plasma albumin concentration in the patient was reduced (6.7 vs. 37.0 +/- 2.6 g/L). Albumin FSR (= FCR in steady state) was increased compared to controls. The ASR (absolute synthesis rate) of albumin was decreased based on the enrichment in plasma valine and KIV, but estimated to be normal based on VLDL apoB100 at plateau compared to controls. Direct estimation of albumin FCR rejected the latter. No mutation was found in the transcribed region of albumin gene. The exact mass of albumin (66.493 Da) was not different from controls. CONCLUSION: The hypoalbuminemia was a result of accelerated clearance of albumin from plasma in addition to defective albumin synthesis. This study also shows that the chosen method of the precursor pool could lead to misinterpretation of data in hepatic protein synthesis.
Asunto(s)
Hipoalbuminemia/metabolismo , Albúmina Sérica/metabolismo , Adulto , Aminoácidos/aislamiento & purificación , Aminoácidos/metabolismo , Apolipoproteínas B/clasificación , Apolipoproteínas B/aislamiento & purificación , Apolipoproteínas B/metabolismo , Electroforesis de las Proteínas Sanguíneas , Isótopos de Carbono , Grupos Control , ADN/análisis , ADN/genética , ADN/metabolismo , Humanos , Cinética , Masculino , Modelos Biológicos , Ácidos Pentanoicos/aislamiento & purificación , Ácidos Pentanoicos/metabolismo , Albúmina Sérica/genética , Espectrometría de Masa por Ionización de Electrospray , Valina/metabolismo , Valina/farmacocinéticaRESUMEN
We develop a hypothesis of lipid transport in blood which differs significantly from commonly used one. In any organism hydrophobic substances transport in aqueous medium functions on the base of the some principles. Hence: (a) lipoproteins transport mainly fatty acids; (b) lopoprotein structure are based on the protein chemistry principles; (c) all lipiproteins are build up according to a single principle and are bilayers--protein: lipid; (d) apolipoprotein is a protein which binds one lipid class, determines the peculiarities of structure and function of transporting macromolecule and disturbs fatty acids transport in blood at inherent synthesis absence or change of apoprotein primary structure; (e) only fatty acids and all their derivatives are lipids. Thus cholesterol being an alcohol is nor a lipid, but cholesrteryl esters with fatty acids are complicated lipids. Thus triacylycerides in blood are the transporting form of saturated fatty acids, but phospholipids--the transporting form of polyenic fatty acids. High density lipoproteins transfer fatty acids in polar esters only, but apoB macromolecules--only in nonpolar. At first, cholesterol is a factor of short-time adaptation to medium change. At second, cholesterol provides active transport of polyenoic fatty acids to cell forming functional circulation of cholesterol. Blood cholesterol is the test of cell deficiency of polyenoic omega-3 fatty acids.
Asunto(s)
Ácidos Grasos/sangre , Lipoproteínas/sangre , Animales , Apolipoproteína B-100 , Apolipoproteínas/sangre , Apolipoproteínas B/sangre , Apolipoproteínas B/clasificación , Transporte Biológico Activo , Ácidos Grasos Omega-3/sangre , Humanos , Sustancias Macromoleculares , Receptores de Lipoproteína/sangreRESUMEN
Impaired postprandial lipoprotein metabolism has been found to be related to the extent of coronary artery disease. Moreover, since dyslipoproteinemias are associated with impaired hemorrheology, we investigated the effect of postprandial hypertriglyceridemia on hemorrheological parameters before and after triglyceride-lowering therapy. Triglyceride-rich lipoproteins (TRLs) separated by ultracentrifugation (d < 1.006 g/dL) and chylomicrons and chylomicron remnants (quantified by apolipoprotein [apo] B-48 determination) were determined after a fat load in 10 patients with familial hypertriglyceridemia before and after therapy with gemfibrozil (900 mg daily). Lipid and hemorrheological parameters (plasma and whole-blood viscosity [PV and BV], red cell aggregation [RCA], hematocrit, and fibrinogen) were determined at baseline and every hour up to 6 hours postprandially. Fasting total triglycerides and TRL triglycerides significantly decreased with gemfibrozil therapy (P < .01). Total triglycerides postprandially increased from 9.53 +/- 1.72 to 14.47 +/- 2.07 mmol/L (TRL triglycerides by 61%) before therapy (P < .05) and from 4.61 +/- 1.28 to 7.17 +/- 0.99 mmol/L (TRL triglycerides by 57%) after therapy (P < .05). The postprandial TRL apo B increase was reduced with gemfibrozil (from 11.6 +/- 2.8 to 20.7 +/- 5.0 mg/dL with therapy v 19.0 +/- 7.6 to 33.0 +/- 12.5 mg/dL before therapy, P < .05, respectively) with a proportionally greater increase in apo B-48 (119% and 169%, respectively) compared with apo B-100 (64% and 64%, respectively). Fasting RCA was improved with lipid-lowering therapy (P < .05), but PV, BV, RCA, and fibrinogen did not show any statistically significant postprandial changes either before or after lipid-lowering therapy. In summary, we did not find any statistically significant changes in hemorrheological parameters, despite a strong postprandial increase of triglycerides. In particular, these findings were independent of fasting triglyceride levels. We conclude that triglyceride-lowering therapy by gemfibrozil had no substantial beneficial effects with respect to hemorrheology in patients with familial hypertriglyceridemia.
Asunto(s)
Apolipoproteínas B/sangre , Hiperlipoproteinemia Tipo IV/sangre , Lípidos/sangre , Triglicéridos/sangre , Adulto , Apolipoproteínas B/clasificación , Apolipoproteínas B/efectos de los fármacos , Apolipoproteínas B/metabolismo , Ayuno/sangre , Femenino , Gemfibrozilo/administración & dosificación , Hematócrito , Humanos , Hiperlipoproteinemia Tipo IV/tratamiento farmacológico , Hiperlipoproteinemia Tipo IV/metabolismo , Hipolipemiantes/administración & dosificación , Metabolismo de los Lípidos , Masculino , Periodo Posprandial , Reología , Factores de Tiempo , Triglicéridos/metabolismoRESUMEN
Circulating apolipoprotein B (apoB) exists in two forms; apoB-100 and apoB-48. ApoB-48 is a truncated form of apoB resulting from RNA editing. The editing enzyme, called apobec-1, converts a cytidine (C) at nucleotide 6666 in apoB 100 mRNA to a uridine (U) and changes a CAA codon to an in-frame stop codon, UAA. We have produced a specific rabbit polyclonal antiserum against apobec-1 by genetic immunization. The cDNA of mouse apobec-1 was inserted downstream and in-frame at the BamH I site in the last exon of human growth hormone cDNA driven by a cytomegalovirus promoter. This plasmid was injected together with another plasmid expressing granulocyte macrophage colony-stimulating factor into the thigh muscles of a rabbit. The resulting antiserum demonstrated high specificity on Western blots, and inhibited the apoB mRNA editing activity of mouse liver extract in a dose-dependent manner. This report demonstrates that DNA immunization is a powerful technique that can be readily applied to other sparse or difficult-to-purify proteins in lipid metabolism.
Asunto(s)
Anticuerpos/farmacología , Citidina Desaminasa/antagonistas & inhibidores , Inmunización/métodos , Desaminasas APOBEC-1 , Adenoviridae/metabolismo , Animales , Anticuerpos/aislamiento & purificación , Apolipoproteínas B/sangre , Apolipoproteínas B/clasificación , Apolipoproteínas B/genética , Western Blotting , Citidina Desaminasa/inmunología , Citidina Desaminasa/metabolismo , ADN Complementario/genética , ADN Complementario/inmunología , Epítopos/química , Epítopos/inmunología , Genes Reporteros , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Hormona del Crecimiento/genética , Hígado/enzimología , Ratones , Plásmidos/genética , Plásmidos/inmunología , Edición de ARN/genética , Edición de ARN/inmunología , ARN Mensajero/metabolismo , Conejos , Transformación GenéticaRESUMEN
La utilización de la cromatografía de afinidad con concanavalina A o de cromatografía de inmunoafinidad con anticuerpos anti apoB permite obtener dos grupos de lipoproteínas: las que contienen apoA y las que contienen apoB. El subfraccionamiento por cromatografía de inmunoafinidad secuencial de las partículas lipoproteicas que contienen apoA permite obtener a su vez tres mayores partículas lipoproteicas: LP-A-I, LP-A-I:A-II y LP-A-II. El subfraccionamiento a través de inmunoprecipitación secuencial o cromatografía de inmunoafinidad secuencial de las partículas lipoproteicas que contienen apoB permite obtener cinco mayores grupos de partículas: LP-B, LP-B:C, LP-B:E, LP-B:C:E y LP-A-II:B. La diferencia entre normo e hiperlipoproteinémicos sería el resultado de cambios cuantitativos (y no cualitativos) de las partículas lipoproteicas. En hipercolesterolémicos se destaca un aumento de LP-B en tanto que en hipertrigliceridémicos aumentan la LP-B-C y LP-B:C:E. Las drogas hipolipemiantes, independientemente de su mecanismo de acción, afectan en diferentes sentidos las concentraciones de las partículas lipoproteicas que contienen apoA y apoB. Bajas concentraciones de LP-A-I y elevadas de LP-B:C y LP-B:C:E se asocian con riesgo aterogénico
Asunto(s)
Humanos , Masculino , Femenino , Apolipoproteínas A/aislamiento & purificación , Apolipoproteínas B/aislamiento & purificación , Apolipoproteínas/aislamiento & purificación , Cromatografía de Afinidad/normas , Reacción de Inmunoadherencia/normas , Apolipoproteínas A/clasificación , Apolipoproteínas B/clasificación , Apolipoproteínas B/metabolismo , Apolipoproteínas/clasificación , Apolipoproteínas/sangre , Aterosclerosis/fisiopatología , Fraccionamiento Químico , Gemfibrozilo/uso terapéutico , Hiperlipoproteinemias/diagnóstico , Hiperlipoproteinemias/tratamiento farmacológicoRESUMEN
La utilización de la cromatografía de afinidad con concanavalina A o de cromatografía de inmunoafinidad con anticuerpos anti apoB permite obtener dos grupos de lipoproteínas: las que contienen apoA y las que contienen apoB. El subfraccionamiento por cromatografía de inmunoafinidad secuencial de las partículas lipoproteicas que contienen apoA permite obtener a su vez tres mayores partículas lipoproteicas: LP-A-I, LP-A-I:A-II y LP-A-II. El subfraccionamiento a través de inmunoprecipitación secuencial o cromatografía de inmunoafinidad secuencial de las partículas lipoproteicas que contienen apoB permite obtener cinco mayores grupos de partículas: LP-B, LP-B:C, LP-B:E, LP-B:C:E y LP-A-II:B. La diferencia entre normo e hiperlipoproteinémicos sería el resultado de cambios cuantitativos (y no cualitativos) de las partículas lipoproteicas. En hipercolesterolémicos se destaca un aumento de LP-B en tanto que en hipertrigliceridémicos aumentan la LP-B-C y LP-B:C:E. Las drogas hipolipemiantes, independientemente de su mecanismo de acción, afectan en diferentes sentidos las concentraciones de las partículas lipoproteicas que contienen apoA y apoB. Bajas concentraciones de LP-A-I y elevadas de LP-B:C y LP-B:C:E se asocian con riesgo aterogénico
Asunto(s)
Humanos , Masculino , Femenino , Apolipoproteínas/aislamiento & purificación , Apolipoproteínas A/aislamiento & purificación , Apolipoproteínas B/aislamiento & purificación , Cromatografía de Afinidad/normas , Reacción de Inmunoadherencia/normas , Apolipoproteínas/clasificación , Apolipoproteínas/sangre , Apolipoproteínas A/clasificación , Apolipoproteínas B/clasificación , Apolipoproteínas B/metabolismo , Fraccionamiento Químico/métodos , Hiperlipoproteinemias/diagnóstico , Hiperlipoproteinemias/tratamiento farmacológico , Aterosclerosis/fisiopatología , Gemfibrozilo/uso terapéuticoRESUMEN
A monoclonal antibody (MB-19) was used to investigate the polymorphism of apolipoprotein B in a large East Finnish family and in unrelated subjects. Apolipoprotein B was shown to exhibit high, intermediate or low affinity binding to this antibody. Thus, MB-19 bound strongly to the Ag(c) epitope, an Ag antigenic domain previously characterized by human antisera, while it bound only weakly to the allelic epitope Ag(g). It proved useful for the detection of the two corresponding allelic apoB species designated apoBc (= high affinity binding) and apoBg (= low affinity binding), and for confirming their co-dominant transmission. Intermediate binding resulted from the presence of a mixture of both apoB populations in heterozygous subjects.