All practically possible hydrogen abstraction reactions for guanosine and uridine have been investigated through quantum chemical calculations of energy barriers and rate constants. This was done at ...the level of density functional theory (DFT) with the ωB97X-D functional and the 6-311++G(2df,2pd) Pople basis set. Transition state theory with the Eckart tunneling correction was used to calculate the rate constants. The results show that the reaction involving the hydrogen labelled C4' in the ribofuranose part has the largest rate constant for guanosine with the value 5.097×1010 L mol-1s-1 and the largest for uridine with the value 1.62×1010 L mol-1s-1. Based on the results for these two nucleosides, there is a noticeable similarity between the rate constants in the ribofuranose part of the molecule, even though they are bound to two entirely different nucleobases.
Previous theoretical investigations of the reactions between an OH radical and a nucleobase have stated the most important pathways to be the C5-C6 addition for pyrimidines and the C8 addition for ...purines. Furthermore, the abstraction of a methyl hydrogen from thymine has also been proven an important pathway. The conclusions were based solely on gas-phase calculations and harmonic vibrational frequencies. In this paper, we supplement the calculations by applying solvent corrections through the polarizable continuum model (PCM) solvent model and applying anharmonicity in order to determine the importance of anharmonicity and solvent effects. Density functional theory (DFT) at the ωB97-D/6-311++G(2df,2pd) level with the Eckart tunneling correction is used. The total reaction rate constants are found to be 1.48 ×10-13 cm
molecules
s
for adenine, 1.02 ×10-11 cm
molecules
s
for guanine, 5.52 ×10-13 cm
molecules
s
for thymine, 1.47 ×10-13 cm
molecules
s
for cytosine and 7.59 ×10-14 cm
molecules
s
for uracil. These rates are found to be approximately two orders of magnitude larger than experimental values. We find that the tendencies observed for preferred pathways for reactions calculated in a solvent are comparable to the preferred pathways for reactions calculated in gas phase. We conclude that applying a solvent has a larger impact on more parameters compared to the inclusion of anharmonicity. For some reactions the inclusion of anharmonicity has no effect, whereas for others it does impact the energetics.
Due to the importance of predicting static and dynamic polarizabilities, the performance of various correlated linear response methods including random phase approximation (RPA), RPA(D), ...higher-order random phase approximation (HRPA), HRPA(D), second-order polarization propagator approximation (SOPPA), SOPPA(CC2), SOPPA(CCSD), CC2, and CCSD has been evaluated against CCSD(T) (static case) and CCSD (dynamic cases) for the T145 set of 145 organic molecules. The benchmark reveals that the HRPA(D) method has the best performance for both static and dynamic polarizabilities apart from CCSD. RPA(D) ranks second for the dynamic cases and third for the static case. Using coupled-cluster amplitudes in SOPPA(CCSD) and SOPPA(CC2), the SOPPA results are significantly improved. The HRPA method has the largest deviations from the reference values for both cases. In general, according to the performance and computational cost of the methods, the HRPA(D) and RPA(D) methods are proposed for calculations of static and dynamic polarizabilities of this and similar sets of molecules.
BACKGROUND
Both maternal and paternal factors have been suggested to influence a couple's fecundity. To investigate this, we examined the role of several maternal and paternal lifestyle and ...socio-demographic factors as determinants of time to pregnancy (TTP) in a Dutch birth-cohort.
METHODS
Groningen Expert Center for Kids with Obesity (GECKO) Drenthe is a population-based birth-cohort study of children born between April 2006 and April 2007 in Drenthe, a province of The Netherlands. Both partners received extensive questionnaires during pregnancy. Univariable and multivariable Cox regression analyses were used to determine the impact of the investigated factors on TTP.
RESULTS
A total of 4778 children were born, and the parents of 2997 children (63%) gave their consent to participate. After excluding unintended pregnancies and pregnancies as a result of fertility treatment, the data of 1924 couples were available for analysis. Hazards ratios and 95% confidence intervals of factors influencing TTP in multivariable Cox regression analysis were: maternal age 1.23 (0.98–1.54) for age <25 years, 1.17 (1.03–1.32) for age 25–30 years and 0.72 (0.61–0.85) for age >35 years (reference category: 30–35 years); paternal age: 1.31 (0.94–1.82) for age <25 years, 1.11 (0.97–1.28) for age 25–30 years and 0.91 (0.80–1.04 for age >35 years (reference category: 30–35 years); nulliparity: 0.76 (0.68–0.85) versus multiparity; menstrual cycle length: 1.12 (0.95–1.30) for 3 weeks, 0.72 (0.62–0.83) for 4–6 weeks, 0.68 (0.40–1.16) for >6 weeks and 0.66 (0.54–0.81) for irregular cycle (reference category: 4 weeks); prior contraceptive use: 0.78 (0.67–0.91) for no contraception, 1.68 (1.45–1.95) for condom use, 1.08 (0.89–1.33) for condom use combined with oral contraception, 1.40 (1.16–1.70) for intrauterine device and 0.50 (0.25–1.01) for contraceptive injection (reference category: oral contraception); and maternal educational level 0.75 (0.62–0.92) for low education level and 0.81 (0.73–0.90) for medium educational level (reference category: high educational level).
CONCLUSIONS
This population-based birth-cohort study performed in fertile couples who had conceived revealed neither maternal nor paternal modifiable lifestyle factors were significantly associated with TTP after adjustment for confounding by socio-demographic factors. In contrast, several non-modifiable maternal socio-demographic factors are significant predictors of a couple's fecundity.
Human sewage contamination of surface waters is a major human health concern. We found urban stormwater systems that collect and convey runoff from impervious surfaces act as a conduit for sewage ...originating from breeches in sanitary sewer infrastructure. A total of 828 samples at 45 stormwater outfalls were collected over a four-year period and assessed by culture based methods, PCR, and quantitative PCR (qPCR) to test for traditional and alternative indicators of fecal pollution. All outfalls had the HF183 (human)
Bacteroides genetic marker detected in at least one sample, suggesting sewage contamination is nearly ubiquitous in the urban environment. However, most outfalls were intermittently positive, ranging from detection in 11%–100% of the samples. Positive results did not correlate with seasonality, rainfall amounts, or days since previous rainfall. Approximately two-thirds of the outfalls had high (>5000 copy number, i.e. CN, per 100 ml) or moderate levels (1000–5000 CN per 100 ml) of the human
Bacteroides genetic marker.
Escherichia coli (
E. coli) and enterococci levels did not correlate to human
Bacteroides. A total of 66% of all outfall samples had standard fecal indicator levels above 10,000 CFU per 100 ml. A tiered assessment using this benchmark to identify high priority sites would have failed to flag 35% of the samples that had evidence of sewage contamination. In addition, high fecal indicators would have flagged 33% of samples as priority that had low or no evidence of sewage. Enteric virus levels in one outfall with high levels of the human
Bacteroides genetic marker were similar to untreated wastewater, which illustrates stormwater can serve as a pathway for pathogen contamination. The major source of fecal pollution at four of five river sites that receive stormwater discharge appeared to be from sewage sources rather than non-human sources based on the ratios of human
Bacteroides to total
Bacteroides spp. This study shows the feasibility and benefits of employing molecular methods to test for alternative indicators of fecal pollution to identify sewage sources and potential health risks and for prioritization of remediation efforts.
► Human sewage contamination in urban stormwater is a chronic and widespread problem. ► Human
Bacteroides was detected intermittently, indicating complex mechanisms. ► High levels of human
Bacteroides were found with no correlation to fecal indicators. ► Molecular methods are an effective approach to protecting health and infrastructure.
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