PubMed Health⌕ Search

Biomedical subjects

James M Nicholson

Publications and source records attributed to James M Nicholson.

8 recordsLinked to original sources
PubMed2006

The oxidised histone octamer does not form a H3 disulphide bond.

A H3 dimer band is produced when purified native histone octamers are run on an SDS-PAGE gel in a beta-mercaptoethanol-free environment. To investigate this, native histone octamer crystals, derived from chicken erythrocytes, and of structure (H2A-H2B)-(H4-H3)-(H3'-H4')-(H2B'-H2A'), were grown in 2 M KCl, 1.35 M potassium phosphates and 250-350 microM of the oxidising agent S-nitrosoglutathione, pH 6.9. X-ray diffraction data were acquired to 2.10 A resolution, yielding a structure with an Rwork value of 18.6% and an Rfree of 22.5%. The space group is P6(5), the asymmetric unit of which contains one complete octamer. Compared to the 1.90 A resolution, unoxidised native histone octamer structure, the crystals show a reduction of 2.5% in the c-axis of the unit cell, and free-energy calculations reveal that the H3-H3' dimer interface in the latter has become thermodynamically stable, in contrast to the former. Although the inter-sulphur distance of the two H3 cysteines in the oxidised native histone octamer has reduced to 6 A from the 7 A of the unoxidised form, analysis of the hydrogen bonds that constitute the (H4-H3)-(H3'-H4') tetramer indicates that the formation of a disulphide bond in the H3-H3' dimer interface is incompatible with stable tetramer formation. The biochemical and biophysical evidence, taken as a whole, is indicative of crystals that have a stable H3-H3' dimer interface, possibly extending to the interface within an isolated H3-H3' dimer, observed in SDS-PAGE gels.

Animals↗
PubMed2006

Induction of labor and cesarean delivery by gestational age.

OBJECTIVE: Studies of cesarean delivery (CD) rates among women undergoing induction of labor (IOL) often compare such women to women experiencing spontaneous labor at similar gestational ages. We sought to examine the association between IOL at various gestational ages and CD, accounting for the effect of increased gestational age among the comparison group who were managed expectantly. STUDY DESIGN: We conducted a retrospective cohort study of all term, singleton, cephalic presentation pregnancies delivered at our institution over 15 years excluding cesarean deliveries before labor. For each gestational age of induction, we created a comparison group of women who were undelivered at that gestational age, and who experienced labor at some future gestational age. RESULTS: In women undergoing IOL at 38 weeks gestation, the CD rate was 11.9% as compared to 13.3% (P = .42) of women beyond 38 weeks gestation. The CD rate for induction of labor compared to ongoing pregnancy was 14.3% versus 15.0% (P = .62) at 39 weeks, 20.4% versus 19.0% (P = .41) at 40 weeks, and 24.3% versus 26.0% (P = .39) at 41 weeks. When controlling for potential confounding, there was a higher rate of CD among women with expectant management beyond 38 weeks (adjusted odds ratio [AOR] 1.80; 95% CI 1.29-2.53), 39 weeks (1.39; 95% CI 1.08-1.80), and 40 weeks (AOR 1.27; 95% CI 1.00-1.62). CONCLUSION: Our findings suggest that IOL may not increase a woman's risk of CD when compared to expectant management. While this question has been addressed prospectively at 41 weeks gestation, it requires further examination at earlier gestations and among various subgroups.

Cesarean Section↗
PubMed2005

High-resolution structure of the native histone octamer.

Crystals of native histone octamers (H2A-H2B)-(H4-H3)-(H3'-H4')-(H2B'-H2A') from chick erythrocytes in 2 M KCl, 1.35 M potassium phosphate pH 6.9 diffract X-rays to 1.90 A resolution, yielding a structure with an R(work) value of 18.7% and an Rfree of 22.2%. The crystal space group is P6(5), the asymmetric unit of which contains one complete octamer. This high-resolution model of the histone-core octamer allows further insight into intermolecular interactions, including water molecules, that dock the histone dimers to the tetramer in the nucleosome-core particle and have relevance to nucleosome remodelling. The three key areas analysed are the H2A'-H3-H4 molecular cluster (also H2A-H3'-H4'), the H4-H2B' interaction (also H4'-H2B) and the H2A'-H4 beta-sheet interaction (also H2A-H4'). The latter of these three regions is important to nucleosome remodelling by RNA polymerase II, as it is shown to be a likely core-histone binding site, and its disruption creates an instability in the nucleosome-core particle. A majority of the water molecules in the high-resolution octamer have positions that correlate to similar positions in the high-resolution nucleosome-core particle structure, suggesting that the high-resolution octamer model can be used for comparative studies with the high-resolution nucleosome-core particle.

Animals↗
PubMed2004

Active management of risk in pregnancy at term in an urban population: an association between a higher induction of labor rate and a lower cesarean delivery rate.

OBJECTIVE: The purpose of this study was to determine whether exposure to an alternative method of care, called the active management of risk in pregnancy at term, was associated with a lower group cesarean delivery rate. STUDY DESIGN: Active management of risk in pregnancy at term used risk factors for cesarean delivery to guide an increased use of labor induction. A retrospective cohort design was used to compare clinical outcomes of 100 pregnant women who were exposed to active management of risk in pregnancy at term to 300 randomly selected subjects who received standard management. RESULTS: The 2 groups had comparable levels of prenatal risk. The group exposed to the active management of risk in pregnancy at term exposure group encountered a higher induction rate (63% vs 25.7%; P < .001) and a lower cesarean delivery rate (4% vs 16.7%; P = .01). Findings were similar for both nulliparous and multiparous subgroups. Active management of risk in pregnancy at term exposure was not associated with higher rates of other major birth outcomes. CONCLUSION: Exposure to the active management of risk in pregnancy at term exposure was associated with a significantly lower group cesarean delivery rate. A prospective randomized trial that involved active management of risk in pregnancy at term exposure is needed to further explore this association.

Adult↗
PubMed2004

Histone structures: targets for modifications by molecular assemblies.

The core histone proteins contain modification sites that are key elements in the regulation of the cell cycle, DNA replication and repair with histone assembly, control of gene expression, and transcriptional elongation. Much work has been done on the various molecular assemblies that remodel nucleosomes, methylate, ubiquitinate, and cause ADP-ribosylation of histones, and acetylate and phosphorylate core histone tails. The core histones are the final targets of the enzymes in the molecular assemblies. What structural changes in the histones are correlated with these modifications? This paper considers the high-resolution structure of the histone octamer and stresses the importance of histone docking sequences in the binding of the two (H2A-H2B) dimers to the (H3-H4)(2) tetramer. There is an extensive acid-base area of interaction between histone octamers in crystals at high salt, which may have implications for nucleosome remodeling. We show that there are regions of high alpha-helix probability in all core histone N-terminal tails in regions where lysine acetylation occurs. There are also consensus sequences spanning up to eight amino acid residues between some histone tail regions. Circular dichroism studies using synchrotron radiation at wavelengths as low as 130 nm are promising for the accurate measurement of changes of histone secondary structure related to function.

Amino Acid Sequence↗