Long AT repeat tracts form non-B DNA structures that stall DNA replication and cause chromosomal breakage. AT repeats are abundant in human common fragile sites (CFSs), genomic regions that undergo breakage under replication stress. Using an in vivo yeast model system containing AT-rich repetitive elements from human CFS FRA16D, we find that DNA polymerase zeta (Pol ζ) is required to prevent breakage and subsequent deletions at hairpin and cruciform forming (AT/TA)n sequences, with little to no role at an (A/T)28 repeat or a control non-structure forming sequence.
View Article and Find Full Text PDFBacterial persistence is a transient, nonheritable physiological state that provides tolerance to bactericidal antibiotics. The stringent response, toxin-antitoxin modules, and stochastic processes, among other mechanisms, play roles in this phenomenon. How persistence is regulated is relatively ill defined.
View Article and Find Full Text PDFIn , OmpF is an important outer membrane protein, which serves as a passive diffusion pore for small compounds including nutrients, antibiotics, and toxic compounds. OmpF expression responds to environmental changes such as temperature, osmolarity, nutrients availability, and toxic compounds via complex regulatory pathways involving transcriptional and post-transcriptional regulation. Our study identified a new regulatory cascade that controls the expression of OmpF porin.
View Article and Find Full Text PDFN-Acetylglucosaminidases (GlcNAcases) play an important role in the remodeling and recycling of bacterial peptidoglycan by degrading the polysaccharide backbone. Genetic deletions of autolysins can impair cell division and growth, suggesting an opportunity for using small molecule autolysin inhibitors both as tools for studying the chemical biology of autolysins and also as antibacterial agents. We report here the synthesis and evaluation of a panel of diamides that inhibit the growth of Bacillus subtilis.
View Article and Find Full Text PDFObjectives: To detail the transition to a totally one-stop wide-awake (OSWA) Dupuytren's contracture surgical service.
Design: Retrospective review of Dupuytren's component of last 1000 OSWA cases.
Setting: The UK's first totally one-stop wide-awake orthopaedic service.
Using (1)H-nuclear magnetic resonance (NMR) spectroscopy and statistical models, we sought to identify ''biomarkers'' present in erythrocytes that would distinguish between women with normal pregnancy and those suffering from preeclampsia, and investigate possible links with previously identified plasma ''markers.'' Erythrocytes from 22 normotensive pregnant women and 15 preeclamptics were analyzed by (1)H Carr-Purcell-Meiboom-Gill (CPMG) NMR. Multivariate analysis and logistic regression were applied to differentiate between the 2 groups of patients, and used to develop a diagnostic model based on the concentrations of the constituents identified as being influential.
View Article and Find Full Text PDFObjectives: There is conflicting literature regarding the correlation between aromatic amino acid concentrations and the occurrence of preeclampsia (PE). The object of this study was to test whether these molecules could enable discrimination between healthy and preeclamptic pregnancies when detected using (1)H nuclear magnetic resonance spectroscopy.
Methods: Plasma samples from 11 normotensive and 11 preeclamptic pregnant women were analyzed using (1)H-NMR.
Eur J Obstet Gynecol Reprod Biol
September 2008
Objective: Pre-eclampsia (PET) remains a leading cause of maternal and neonatal morbidity and mortality. Although its pathophysiology involves an underlying inflammatory dysfunction, it is unclear how this may be affected by increasing gestational age, particularly in relation to the time of onset of disease. Murine studies have indicated that a progressive increase in serum inflammatory profile is a physiological feature of normal gestation.
View Article and Find Full Text PDFObjective: Using (1)H-nuclear magnetic resonance spectroscopy and chemometrics, we sought to establish the metabolic profile for preeclampsia and to identify biomarkers that would permit a distinction between women with a normal pregnancy and those suffering from preeclampsia.
Methods: Plasma samples from 11 normotensive pregnant women and 11 women with preeclampsia were analyzed. Principal component analysis was applied to differentiate between the two groups of patients.