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Whole-genome sampling analysis with Affymetrix GeneChip Human Mapping 100K arrays is used to study 100 children with idiopathic mental retardation and normal results of standard chromosomal analysis. It is found that this technology can detect at least twice as many potentially pathogenic de novo copy-number variants, as conventional cytogenetic analysis can in people with mental retardation.

The structure of sickle cell hemoglobin (Hb S) fibers was probed using UV resonance Raman spectroscopy. For these studies a functional analogue of Hb S, was used to study structural changes that accompany fiber formation.

The pH-induced unfolding and refolding of the carbon monoxide-bound derivative of horse skeletal myoglobin encapsulated in porous sol-gels is probed using several optical techniques in conjunction with different unfolding/refolding protocols. UV resonance Raman spectroscopy and fluorescence are used to monitor the unfolding of the globin and exposure of the A helix to solvent.

The photochemistry of the K-590 intermediate in the room-temperature bacteriorhodopsin photocycle is examined with picosecond time resolution. The wavelength of the laser pulse is selected to optimize their respective functions in terms of photolysis or monitoring changes in absorbance.

The plain mesoporous SBA silicates and mesoporous SBA silicates with surface ethyl, carboxylate, and ethylenediaminetriacetic acid groups are prepared by direct synthesis. The surface area and structural order were dependent upon the amount of added functionalized silane used during synthesis.

The blue copper sites in Cucumis sativus stellacyanin and Rhus vernicifera stellacyanin are investigated by X-ray absorption spectroscopy (XAS) in order to probe the effects of axial amide coordination. Blue copper proteins exhibit high-redox potentials and rapid electron-transfer rates compared to normal tetragonal copper complexes.

A study was conducted on the vibrational dynamics of the heme active site of deoxyhemoglobin (dHb) during photoexcitation using transient resonance Raman spectroscopy. The findings indicate that vibrational dynamics of the heme active site of dHb are mode specific. Furthermore, vibrational energy redistribution and relaxation can be key factors in the dynamics of large molecules on time scales as long as several picoseconds.

The leptin receptor variant, Ob-Rb, undergoes abnormal splicing in the C57BL/Ks mice containing a mutant diabetic (db) gene. Abnormal splicing of the protein results in a loss of the cytoplasmic area which is involved in signal transduction. Ob-Rb is expressed in high concentrations in the hypothalamus. Signal transduction by a hypothalamic leptin receptor is probably essential for the leptin's activity in decreasing weight. The leptin receptor, which maps the position of the db gene in mouse genome, has about six alternatively spliced forms.

The structure of HIV-1 reverse transcriptase reveals a peculiar aspect of polymerase domain, assuming a different structure in the two subunits p51 and p66. However, it has the same polypeptide chain sequence as other transcriptases. The two subunits interact to produce one polymerase cleft that binds primer-template.

Studies on the co-crystal structure of HIV virus type 1 reverse transcriptase and nevirapine reveal that the induced mutations produce steric clashes and remove favorable protein-drug contacts. Four conserved residues, Phe-227, Trp-229, Leu-234 and Tyr-319 do not produce viable virus. Inhibitor designs that interact with the conserved residues may produce drugs less susceptible escape mutations.

Lithium taken for manic-depressive disorders during pregnancy may not seriously affect fetal development. Researchers studied data to evaluate the risk of birth defects related to exposure to lithium. Studies done in the 1970s found a strong relation between Ebstein's anomaly of the heart and lithium therapy during pregnancy, with an estimated relative risk of 400. Animal studies also supported the relation. Studies of birth defects among infants of women treated with lithium completed in the 1980s indicated a much lower risk of developmental defects. Four of 59 infants in one study had congenital heart disease, but none had Ebstein's anomaly. In a second study, the incidence of defects was not significantly different among exposed and unexposed infants. In four other studies, combined results indicate that no mothers of 208 children with Ebstein's anomaly received lithium during pregnancy. In contrast, two mothers of 398 healthy infants received lithium therapy., Objective.--To reevaluate the risk associated with in utero exposure to lithium. Data Sources and Study Selection.--Data were obtained from all published studies, in multiple languages, referenced in MEDLINE, Toxline, and the Lithium information Center databases. Unpublished studies were not included. The search terms were lithium, pregnancy, teratogen, abnormalities (drug induced), Ebstein's anomaly, and adverse effects. Data Extraction and Synthesis.--In the 1970s a very strong association was suggested between maternal lithium treatment during pregnancy and Ebstein's anomaly of the heart in the offspring. The relative risk for Ebstein's anomaly among such children was estimated to be 400 on the basis of data collected from a registry of voluntarily submitted cases. More recent controlled epidemiologic studies have consistently shown a lower risk. No women who took lithium during pregnancy were found among four case-control studies of Ebstein's anomaly involving 25, 34, 59, and 89 affected children, respectively. In two cohort studies, risk ratios of 3.0 (95% confidence interval [CI], 1.2 to 7.7) and 1.5 (95% CI, 0.4 to 6.8) for all congenital anomalies have been observed. The risk ratios for cardiac malformations in these studies were 7.7 (95% CI, 1.5 to 41.2) and 1.2 (95% CI, 0.1 to 18.3), respectively. Conclusion.--While initial information regarding the teratogenic risk of lithium treatment was derived from biased retrospective reports, more recent epidemiologic data indicate that the teratogenic risk of first-trimester lithium exposure is lower than previously suggested. The clinical management of women with bipolar disorder who have childbearing potential should be modified with this revised risk estimate. (JAMA. 1994;271:146-150)

Time-resolved resonance Raman spectroscopy was used to analyze geminate heme-CO rebinding in photolyzed HbCO. It was found that the Fe-CO bond strengths and configurations of the geminate rebound sites is the same as thoseof equilibrium configurations of HbCO within 500 nanoseconds of CO photolysis. At room temperature, interconversion between the HbCO configurations occurs on a submicrosecond time scale.

A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase heterodimer complexed with nevirapine, a drug with potential for treatment of AIDS, reveals an asymmetric dimer. The polymerase [...]