An Upstream Hfq Binding Site in the fhlA mRNA Leader Region Facilitates the OxyS-fhlA Interaction

To survive, bacteria must be able to adapt to environmental stresses. Small regulatory RNAs have been implicated as intermediates in a variety of stress-response pathways allowing dynamic gene regulation. The RNA binding protein Hfq facilitates this process in many cases, helping sRNAs base pair with their target mRNAs and initiate gene regulation. Although Hfq has been identified as a critical component in many RNPs, the manner by which Hfq controls these interactions is not known.To test the requirement of Hfq in these mRNA-sRNA complexes, the OxyS-fhlA system was used as a model. OxyS is induced in response to oxidative stress and down regulates the translation of fhlA, a gene encoding a transcriptional activator for formate metabolism. Biophysical characterization of this system previously used a minimal construct of the fhlA mRNA which inadvertently removed a critical element within the leader sequence of this mRNA that effected thermodynamics and kinetics for the interaction with Hfq.Herein, we report thermodynamic, kinetic and structural mapping studies during binary and ternary complex formation between Hfq, OxyS and fhlA mRNA. Hfq binds fhlA mRNA using both the proximal and distal surfaces and stimulates association kinetics between the sRNA and mRNA but remains bound to fhlA forming a ternary complex. The upstream Hfq binding element within fhlA is similar to (ARN)(x) elements recently identified in other mRNAs regulated by Hfq. This work leads to a kinetic model for the dynamics of these complexes and the regulation of gene expression by bacterial sRNAs

Assessment of ambient air pollution in the Waterberg Priority Area 2012-2015

The Waterberg Priority Area ambient air quality monitoring network was established in 2012 to monitor the ambient air quality in the Waterberg Air Quality Priority Area. Three monitoring stations were established in Lephalale, Thabazimbi and Mokopane. The monitoring stations measure the concentrations of PM10, PM2.5, SO2, NOx, CO, O3, BTEX and meteorological parameters. Hourly data for a 31 month period (October 2012-April 2015) was obtained from the South African Air Quality Information System (SAAQIS) and analysed to assess patterns in atmospheric concentrations, including seasonal and diurnal patterns of the ambient concentrations and to assess the impacts that such reported pollution concentration may have. Local source regions for SO2, PM10, PM2.5 and O3 were identified and trends in the recorded concentrations are discussed

Ranking ligand affinity for the DNA minor groove by experiment and simulation

The structural and thermodynamic basis for the strength and selectivity of the interactions of minor-groove binders (MGBs) with DNA is not fully understood. In 2003 we reported the first example of a thiazole containing MGB that bound in a phase shifted pattern that spanned 6 base-pairs rather than the usual 4 (for tricyclic distamycin-like compounds). Since then, using DNA footprinting, nuclear magnetic resonance spectroscopy, isothermal titration calorimetry and molecular dynamics, we have established that the flanking bases around the central 4 being read by the ligand have subtle effects on recognition. We have investigated the effect of these flanking sequences on binding and the reasons for the differences and established a computational method to rank ligand affinity against varying DNA sequences

Measurement of atmospheric black carbon in the Vaal Triangle and Highveld Priority Areas

Atmospheric black carbon is an important atmospheric pollutant; it has impacts on human health and a strong climate impact. Black carbon particles are functionally defined by their optical properties (viz. characteristics in light absorption). As a result, black carbon particles are derived from a wide range of sources, but are largely the result of incomplete combustion processes. In order to quantify the atmospheric load of black carbon particles, multi angle absorption photometer (MAAP) instruments have been installed in 8 of the ambient air quality monitoring stations in the Vaal Triangle and Highveld Priority areas. Three of the instruments have been in operation since 2012 and the other 5 were installed in August 2013. This paper presents an analysis of the initial black carbon monitoring data. The impacts of seasonality and meteorological conditions as well as the relationship of the black carbon concentration to PM10and PM2.5 concentrations are discussed

Analysis of a period of elevated ozone concentration reported over the Vaal Triangle on 2 June 2013

A peak in the ambient ozone concentration was observed at three of the six ambient air quality monitoring stations in the Vaal Triangle Airshed Priority Area on the second of June 2013. The ozone peak was associated with elevated concentrations of particulate matter, including PM10, PM2.5 and black carbon, but not sulphur dioxide, oxides of nitrogen, carbon monoxide nor benzene. Back trajectory analysis using Hysplit showed that the air masses containing the high levels of ozone passed over areas influenced by coal fired power stations in the Waterberg, metal processing in the Bojanala region and high intensity fires 30km to 50km upwind of the stations

Water Dynamics at Protein Interfaces: Ultrafast Optical Kerr Effect Study

The behavior of water molecules surrounding a protein can have an important bearing on its structure and function. Consequently, a great deal of attention has been focused on changes in the relaxation dynamics of water when it is located at the protein surface. Here we use the ultrafast optical Kerr effect to study the H-bond structure and dynamics of aqueous solutions of proteins. Measurements are made for three proteins as a function of concentration. We find that the water dynamics in the first solvation layer of the proteins are slowed by up to a factor of 8 in comparison to those in bulk water. The most marked slowdown was observed for the most hydrophilic protein studied, bovine serum albumin, whereas the most hydrophobic protein, trypsin, had a slightly smaller effect. The terahertz Raman spectra of these protein solutions resemble those of pure water up to 5 wt % of protein, above which a new feature appears at 80 cm–1, which is assigned to a bending of the protein amide chain

Attraction between DNA molecules mediated by multivalent ions

The effective force between two parallel DNA molecules is calculated as a function of their mutual separation for different valencies of counter- and salt ions and different salt concentrations. Computer simulations of the primitive model are used and the shape of the DNA molecules is accurately modelled using different geometrical shapes. We find that multivalent ions induce a significant attraction between the DNA molecules whose strength can be tuned by the averaged valency of the ions. The physical origin of the attraction is traced back either to electrostatics or to entropic contributions. For multivalent counter- and monovalent salt ions, we find a salt-induced stabilization effect: the force is first attractive but gets repulsive for increasing salt concentration. Furthermore, we show that the multivalent-ion-induced attraction does not necessarily correlate with DNA overcharging.Comment: 51 pages and 13 figure

Adsorption of mono- and multivalent cat- and anions on DNA molecules

Adsorption of monovalent and multivalent cat- and anions on a deoxyribose nucleic acid (DNA) molecule from a salt solution is investigated by computer simulation. The ions are modelled as charged hard spheres, the DNA molecule as a point charge pattern following the double-helical phosphate strands. The geometrical shape of the DNA molecules is modelled on different levels ranging from a simple cylindrical shape to structured models which include the major and minor grooves between the phosphate strands. The densities of the ions adsorbed on the phosphate strands, in the major and in the minor grooves are calculated. First, we find that the adsorption pattern on the DNA surface depends strongly on its geometrical shape: counterions adsorb preferentially along the phosphate strands for a cylindrical model shape, but in the minor groove for a geometrically structured model. Second, we find that an addition of monovalent salt ions results in an increase of the charge density in the minor groove while the total charge density of ions adsorbed in the major groove stays unchanged. The adsorbed ion densities are highly structured along the minor groove while they are almost smeared along the major groove. Furthermore, for a fixed amount of added salt, the major groove cationic charge is independent on the counterion valency. For increasing salt concentration the major groove is neutralized while the total charge adsorbed in the minor groove is constant. DNA overcharging is detected for multivalent salt. Simulations for a larger ion radii, which mimic the effect of the ion hydration, indicate an increased adsorbtion of cations in the major groove.Comment: 34 pages with 14 figure

Quantum Computing and Quantum Simulation with Group-II Atoms

Recent experimental progress in controlling neutral group-II atoms for optical clocks, and in the production of degenerate gases with group-II atoms has given rise to novel opportunities to address challenges in quantum computing and quantum simulation. In these systems, it is possible to encode qubits in nuclear spin states, which are decoupled from the electronic state in the $^1$S$_0$ ground state and the long-lived $^3$P$_0$ metastable state on the clock transition. This leads to quantum computing scenarios where qubits are stored in long lived nuclear spin states, while electronic states can be accessed independently, for cooling of the atoms, as well as manipulation and readout of the qubits. The high nuclear spin in some fermionic isotopes also offers opportunities for the encoding of multiple qubits on a single atom, as well as providing an opportunity for studying many-body physics in systems with a high spin symmetry. Here we review recent experimental and theoretical progress in these areas, and summarise the advantages and challenges for quantum computing and quantum simulation with group-II atoms.Comment: 11 pages, 7 figures, review for special issue of "Quantum Information Processing" on "Quantum Information with Neutral Particles

Effectiveness of a Regional Prepregnancy Care Program in Women With Type 1 and Type 2 Diabetes: Benefits beyond glycemic control

OBJECTIVE: To implement and evaluate a regional prepregnancy care program in women with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Prepregnancy care was promoted among patients and health professionals and delivered across 10 regional maternity units. A prospective cohort study of 680 pregnancies in women with type 1 and type 2 diabetes was performed. Primary outcomes were adverse pregnancy outcome (congenital malformation, stillbirth, or neonatal death), congenital malformation, and indicators of pregnancy preparation (5 mg folic acid, gestational age, and A1C). Comparisons were made with a historical cohort (n = 613 pregnancies) from the same units during 1999-2004. RESULTS: A total of 181 (27%) women attended, and 499 women (73%) did not attend prepregnancy care. Women with prepregnancy care presented earlier (6.7 vs. 7.7 weeks; P < 0.001), were more likely to take 5 mg preconception folic acid (88.2 vs. 26.7%; P < 0.0001) and had lower A1C levels (A1C 6.9 vs. 7.6%; P < 0.0001). They had fewer adverse pregnancy outcomes (1.3 vs. 7.8%; P = 0.009). Multivariate logistic regression confirmed that in addition to glycemic control, lack of prepregnancy care was independently associated with adverse outcome (odds ratio 0.2 [95% CI 0.05-0.89]; P = 0.03). Compared with 1999-2004, folic acid supplementation increased (40.7 vs. 32.5%; P = 0.006) and congenital malformations decreased (4.3 vs. 7.3%; P = 0.04). CONCLUSIONS: Regional prepregnancy care was associated with improved pregnancy preparation and reduced risk of adverse pregnancy outcome in type 1 and type 2 diabetes. Prepregnancy care had benefits beyond improved glycemic control and was a stronger predictor of pregnancy outcome than maternal obesity, ethnicity, or social disadvantage