RESUMEN
XIAP, a member of the inhibitor of apoptosis family of proteins, is a critical regulator of apoptosis. Inhibition of the BIR domain-caspase interaction is a promising approach towards treating cancer. Previous work has been directed towards inhibiting the BIR3-caspase-9 interaction, which blocks the intrinsic apoptotic pathway; selectively inhibiting the BIR2-caspase-3 interaction would also block the extrinsic pathway. The BIR2 domain of XIAP has successfully been crystallized; peptides and small-molecule inhibitors can be soaked into these crystals, which diffract to high resolution. Here, the BIR2 apo crystal structure and the structures of five BIR2-tetrapeptide complexes are described. The structural flexibility observed on comparing these structures, along with a comparison with XIAP BIR3, affords an understanding of the structural elements that drive selectivity between BIR2 and BIR3 and which can be used to design BIR2-selective inhibitors.
Asunto(s)
Caspasa 3/química , Caspasa 3/metabolismo , Inhibidores de Caspasas/química , Proteínas Inhibidoras de la Apoptosis/química , Nucleopoliedrovirus/química , Proteínas Virales/química , Proteína Inhibidora de la Apoptosis Ligada a X/química , Secuencia de Aminoácidos , Apoproteínas/química , Apoproteínas/genética , Apoptosis/genética , Cristalografía por Rayos X , Humanos , Proteínas Inhibidoras de la Apoptosis/genética , Datos de Secuencia Molecular , Familia de Multigenes/genética , Nucleopoliedrovirus/genética , Oligopéptidos/química , Oligopéptidos/genética , Mapeo de Interacción de Proteínas , Estructura Terciaria de Proteína/genética , Proteínas Virales/genética , Proteína Inhibidora de la Apoptosis Ligada a X/genéticaRESUMEN
Anthropogenic activities accelerate fluoride contamination in groundwater, which largely affects public health. Though biochars have been explored for defluoridation, the plasma technology-based production of biochars has not received as considerable attention as other methods and it is also important that biochars be tested on groundwater samples. In the present study, for the first time, we report the preparation of biochars from different parts of Moringa oleifera using thermal plasma processing and demonstrate fluoride adsorption in both synthetic and contaminated groundwater. Water samples were collected from different locations in Nuapada district of Odisha such as Kotamal-Makardampada (20°24'46''N 82°37'19''E), Pandrapathar (20°34'41''N 82°39'25''E), Karlakot-Kadobhata (20°22'52''N 82°37'24''E), Kotamal-Jhakarpada (20°24'35''N 82°37'20''E), and Dohelpada (20°33'50''N 82°38'57''E). The Moringa leaf samples are processed at 1600 °C for 3 min in an inert atmosphere under a continuous flow of argon to get suitable biochars. The plasma-synthesized biochars contain larger exposed surfaces, which are efficient for the adsorption of fluoride. The prepared biochars were highly porous, amorphous, and contain > 72% carbon, which increases the efficiency of defluoridation due to the surface adsorbate site exposed. XRD of the samples showed the presence of calcium hydroxide, magnesium oxide, and calcium oxide, and large peaks of carbon. Raman data showed the double bond of carbon with oxygen in the form of carbonyl bonds, thioether, and sulfhydryl bonds, which contribute to the protonated site for the adsorption of fluoride, and assist in water penetration and swelling of biochars. The biochar of Moringa oleifera is very efficient for the adsorption of fluoride from standard samples as well as groundwater samples up to a concentration of 6 ppm. Conclusively, the present investigation shows that Moringa oleifera leaves are a good alternative adsorbent that could be used for the removal of fluoride from groundwater samples with > 85% removal in 18 h using 1 g biochar for 100 mL or 10 g biochar for 1 L water containing 4 ppm fluoride. To our knowledge, this is the first report on the thermal plasma-based production of Moringa biochars for the removal of fluoride from drinking water.
RESUMEN
OBJECTIVE: In India, Hepatitis B vaccination is recommended at 6 wk except for hospital-deliveries. The authors examined protection afforded by the birth dose. METHODS: A case-control study was done. HBsAg and HBcAb were tested in 2671 children, 1 to 5 y and HBsAb was evaluated in a subset of 1413 children. Vaccination history was recorded. Cases were HBsAg carriers. In another analysis, children who got infected (HBsAg and/or HBcAb positive) were considered as cases. Exposed were the unvaccinated. In another analysis, exposed were those vaccinated without the birth dose. RESULTS: The odds ratio (OR) for HBsAg positivity with birth vaccination was 0.35 (95% CI 0.19-0.66); while with vaccination at 6 wk was 0.29 (95%CI 0.14-0.61), both compared to unvaccinated. Birth vaccination has no added protection when compared to the unvaccinated. Unvaccinated children in index study had HBsAg positivity of 4.38%. The number needed to treat (NNT) to prevent one case of HBsAg positivity was 32.6 (95% CI, 20.9 to 73.6). The odds of getting HBV infection was 0.42 (CI 0.25-0.68) with birth dose and 0.49 (CI 0.30-0.82) without the birth dose compared to the unvaccinated. Protective antibody (HBsAb) was present in about 70% of the vaccinated. In the unimmunised, in the first 2 y HBsAb protection was present in 40%. The odds ratio (OR) for HBsAb in the fully vaccinated between 4 and 5 y was 1.4 (95%CI 0.9-2.18) compared to the unvaccinated. CONCLUSIONS: The present study lends support to the pragmatic approach of the Government to vaccinate babies born at home starting at 6 wk.
Asunto(s)
Vacunas contra Hepatitis B/uso terapéutico , Hepatitis B/prevención & control , Estudios de Casos y Controles , Preescolar , Femenino , Antígenos de Superficie de la Hepatitis B/análisis , Virus de la Hepatitis B , Humanos , India , Lactante , Masculino , VacunaciónRESUMEN
BACKGROUND: ACOG states meconium stained amniotic fluid (MSAF) as one of the historical indicators of perinatal asphyxia. Thick meconium along with other indicators is used to identify babies with severe intrapartum asphyxia. Lactate creatinine ratio (L:C ratio) of 0.64 or higher in first passed urine of babies suffering severe intrapartum asphyxia has been shown to predict Hypoxic Ischaemic Encephalopathy (HIE). Literature review shows that meconium is passed in distress and thin meconium results from mixing and dilution over time, which may be hours to days. Thin meconium may thus be used as an indicator of antepartum asphyxia. We tested L:C ratios in a group of babies born through thin and thick meconium, and for comparison, in a group of babies without meconium at birth. METHODS: 86 consecutive newborns, 36 to 42 weeks of gestation, with meconium staining of liquor, were recruited for the study. 52 voided urine within 6 hours of birth; of these 27 had thick meconium and 25 had thin meconium at birth. 42 others, who did not have meconium or any other signs of asphyxia at birth provided controls. Lactate and creatinine levels in urine were tested by standard enzymatic methods in the three groups. RESULTS: Lactate values are highest in the thin MSAF group followed by the thick MSAF and controls. Creatinine was lowest in the thin MSAF, followed by thick MSAF and controls. Normal babies had an average L:C ratio of 0.13 (+/- 0.09). L:C ratio was more among thin MSAF babies (4.3 +/- 11.94) than thick MSAF babies (0.35 +/- 0.35). Median L:C ratio was also higher in the thin MSAF group. Variation in the values of these parameters is observed to be high in the thin MSAF group as compared to other groups. L:C ratio was above the cutoff of 0.64 of Huang et al in 40% of those with thin meconium. 2 of these developed signs of HIE with convulsions (HIE Sarnat and Sarnat Stage II) during hospital stay. One had L:C Ratio of 93 and the other of 58.6. A smaller proportion (20%) of those with thick meconium had levels above the cutoff and 2 developed HIE and convulsions with L:C ratio of 1.25 and 1.1 respectively. CONCLUSION: In evolving a cutoff of L:C ratios that would be highly sensitive and specific (0.64), Huang et al studied it in a series of babies with severe intrapartum asphyxia. Our study shows that the specificity may not be as good if babies born through thin meconium are also included. L:C ratios are much higher in babies with thin meconium. It may be that meconium alone is not a good indicator of asphyxia and the risk of HIE. However, if the presence of meconium implies asphyxia then perhaps a higher cut-off than 0.64 is needed. L:C ratios should be tested in a larger sample that includes babies with thin meconium, before L:C ratios can be applied universally.
Asunto(s)
Líquido Amniótico/química , Asfixia Neonatal/diagnóstico , Creatinina/orina , Ácido Láctico/orina , Meconio/química , Puntaje de Apgar , Asfixia Neonatal/complicaciones , Femenino , Edad Gestacional , Humanos , Hipoxia-Isquemia Encefálica/etiología , Recién Nacido , Masculino , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To assess the usefulness of clinical risk index of babies (CRIB score) in predicting neonatal mortality in extremely preterm neonates, compared to birth weight and gestation. METHODS: 97 preterm neonates with gestational age less than 31 weeks or birth weight less than or equal to 1500 g were enrolled for the prospective longitudinal study. Relevant neonatal data was recorded. Blood gas analysis results and the maximum and the minimum FiO2 required by babies in first 12 hours of life were noted. Mortality was taken as death while the baby was in nursery. The prediction of mortality by birth weight, gestational age and CRIB score was done using the Logistic model, and expressed as area under the ROC curve. RESULTS: The area under the ROC curve for birth weight, gestational age and CRIB score was almost the same, the areas being 0.829, 0.819 and 0.823 respectively. Hence CRIB score did not fare better than birth weight and gestational age in predicting neonatal mortality. CONCLUSION: The CRIB score did not improve on the ability of birth weight and gestational age to predict neonatal mortality in the study.