Theoretical Ab initio study of the effects of methylation on the nature of hydrogen bonding in A:T base pair

We report the results of a theoretical ab initio study of methylation in Watson-Crick A:T base pairs. Equilibrium geometries were obtained without symmetry restrictions by the gradient procedure at DFT level of theory with the standard 6-31G(d) basis set. Each local minima was verified by energy second derivative calculations. Single-point calculations for the DFT geometries have been performed at the MP2/6-31G(d,p), MP2/6-31++G(d,p), and MP2/6-311++G(2d,2p) levels of theory. The geometrical parameters, relative stabilities and counterpoise corrected interaction energies are reported. In addition, using a variation-perturbation energy decomposition scheme, we have found the important contributions to the total interaction energy.     

Beta-amyloid precursor polypeptide in SAMP8 mice affects learning and memory

Senescence accelerated (SAMP8 [P8]) mice develop age-related deficits in memory and learning. We show that increased expression of amyloid precursor protein (APP) and its mRNA in the hippocampus are also age-related. Immunocytochemical data suggest that a critical amount of APP expression may be needed to generate amyloid (Aβ) protein plaques in the hippocampus. Deficits in acquisition and retention test performance were alleviated by administration of antibody to Aβ protein into the cerebral ventricles. This reversal of cognitive deficits provides a link between increased expression of both APP and Aβ protein and learning and memory loss in these mice.     

The influence of fatness on the likelihood of early-winter pregnancy in muskoxen (Ovibos moschatus)

Among wild ruminants, muskoxen have an exceptional ability to fatten, but their pregnancy rates are variable and often low. To test whether the likelihood of pregnancy in muskoxen is associated with exceptionally good body condition, we used logistic regression analysis with data from 32 pregnant and 18 nonpregnant muskoxen > or = 1.5 yr of age shot in November (1989 to 1992) on Victoria Island in Arctic Canada. We assayed their serum for insulin-like growth factor-1 (IGF-1). All fatness and mass measures were positively related to the likelihood of pregnancy (P < 0.001), with the strongest associations for estimated total fat mass (80% of outcomes predicted correctly) and kidney fat mass (77%), and weaker models for body mass. Pregnancy was less likely to occur in lactating females than in nonlactating ones (P = 0.03). Although IGF-1 concentrations were higher (P = 0.001) in nonlactating females than in lactating ones (28.7 +/- 1.7 vs. 22.5 ng/ml), no association with pregnancy was detected (P = 0.57). Fatness associated with a 50% probability of pregnancy in muskoxen (22% of ingesta-free body mass or 32 kg fat in females > 3.5 yr old) is much higher than in caribou and somewhat higher than in cattle, and this may partly account for the low calving rates often observed in this species.     

Three years of insecticide resistance monitoring in Anopheles gambiae in Burkina Faso: resistance on the rise?

ABSTRACT: Background and methods A longitudinal Anopheles gambiae s.l. insecticide-resistance monitoring programme was established in four sentinel sites in Burkina Faso. For three years, between 2008 and 2010, WHO diagnostic dose assays were used to measure the prevalence of resistance to all the major classes of insecticides at the beginning and end of the malaria transmission season. Species identification and genotyping for target site mutations was also performed and the sporozoite rate in adults determined. RESULTS: At the onset of the study, resistance to DDT and pyrethroids was already prevalent in An. gambiae s.l. from the south-west of the country but mosquitoes from the two sites in central Burkina Faso were largely susceptible. Within three years, DDT and permethrin resistance was established in all four sites. Carbamate and organophosphate resistance remains relatively rare and largely confined to the south-western areas although a small number of bendiocarb survivors were found in all sites by the final round of monitoring. The ace-1R target site resistance allele was present in all localities and its frequency exceeded 20% in 2010 in two of the sites. The frequency of the 1014 F kdr mutation increased throughout the three years and by 2010, the frequency of 1014 F in all sites combined was 0.02 in Anopheles arabiensis, 0.56 in An. gambiae M form and 0.96 in An. gambiae S form. This frequency did not differ significantly between the sites. The 1014 S kdr allele was only found in An. arabiensis but its frequency increased significantly throughout the study (P = 0.0003) and in 2010 the 1014 S allele frequency was 0.08 in An. arabiensis. Maximum sporozoite rates (12%) were observed in Soumousso in 2009 and the difference between sites is significant for each year. CONCLUSION: Pyrethroid and DDT resistance is now established in An. gambiae s.l. throughout Burkina Faso. Results from diagnostic dose assays are highly variable within and between rounds of testing, and hence it is important that resistance monitoring is carried out on more than one occasion before decisions on insecticide procurement for vector control are made. The presence of 1014 S in An. gambiae s.l., in addition to 1014 F, is not unexpected given the recent report of 1014 S in Benin but highlights the importance of monitoring for both mutations throughout the continent. Future research must now focus on the impact that this resistance is having on malaria control in Burkina Faso.     

Towards prenatal biomonitoring in North Carolina: assessing arsenic, cadmium, mercury, and lead levels in pregnant women

Exposure to toxic metals during the prenatal period carries the potential for adverse developmental effects to the fetus, yet such exposure remains largely unmonitored in the United States. The aim of this study was to assess maternal exposure to four toxic metals (arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb)) in a cohort of pregnant women in North Carolina. We analyzed blood samples submitted to the North Carolina Department of Health and Human Services for blood typing to assess toxic metal levels in pregnant women (n = 211) across six North Carolina counties. Whole blood metal concentrations were measured by inductively coupled plasma mass spectrometry. The association between maternal characteristics, including county of residence, age, and race, and metal exposure was analyzed using multiple linear regression analysis. A large fraction of the blood samples showed detectable levels for each of the four metals. Specifically, As (65.7%), Cd (57.3%), Hg (63.8%), and Pb (100%) were detected in blood samples. Moreover, compared with adult females participating in the Fourth National Report on Human Exposure to Environmental Chemicals and guidelines for pregnant women, some women in the sample population exceeded benchmark levels of Cd, Hg, and Pb. Evidence from this pilot study indicates that pregnant women in North Carolina are exposed to As, Cd, Hg, and Pb and suggests that factors related to maternal county of residence and race may impact maternal exposure levels. As increased levels of one or more of these metals in utero have been associated with detrimental developmental and reproductive outcomes, further study is clearly warranted to establish the impacts to newborns.     

Opportunities for Tuberculosis Diagnosis and Prevention among Persons Living with HIV: A Cross-Sectional Study of Policies and Practices at Four Large Ryan White Program-Funded HIV Clinics

Objective

We describe the frequency and attributes of tuberculosis testing and treatment at four publicly-funded HIV clinics.

Methods

We abstracted medical records from a random sample of 600 HIV-infected patients having at least one clinic visit in 2009 at four clinics in New York and Los Angeles Metropolitan Statistical areas. We described testing and treatment for tuberculosis infection (TBI), 2008–2010, and estimated adjusted odds ratios (aORs). We interviewed key informants and described clinic policies and practices.

Results

Of 600 patients, 500 were eligible for testing, and 393 (79%) were tested 2008–2010; 107 (21%) did not receive at least one tuberculin skin test or interferon gamma release assay. Results were positive in 20 (5%) patients, negative in 357 (91%), and unknown in 16 (4%). Fourteen (70%) of 20 patients with TBI initiated treatment at the clinics; only three were documented to have completed treatment. Three hundred twenty three (54%) patients had chest radiography, 346 (58%) had tuberculosis symptom screening, and three had tuberculosis disease (117 per 100,000 person-years, 95% confidence interval (CI) = 101–165). Adjusting for site, non-Hispanic ethnicity (aOR = 4.9, 95% CI = 2.6–9.5), and employment (aOR = 1.9, 95% CI = 1.0–3.4) were associated with TBI testing; female gender (aOR = 2.0, 95% CI = 1.4–3.3), non-black race (aOR = 1.7, 95% CI = 1.3–2.5), and unemployment (aOR = 1.5, 95% CI = 1.1–2.1) were associated with chest radiography. Clinics evaluated TBI testing performance annually and identified challenges to TB prevention.

Conclusions

Study clinics routinely tested patients for TBI, but did not always document treatment. In a population with a high TB rate, ensuring treatment of TBI may enhance TB prevention.     

Tuberculosis Treatment Managed by Providers outside the Public Health Department: Lessons for the Affordable Care Act

Introduction

Tuberculosis (TB) requires at least six months of multidrug treatment and necessitates monitoring for response to treatment. Historically, public health departments (HDs) have cared for most TB patients in the United States. The Affordable Care Act (ACA) provides coverage for uninsured persons and may increase the proportion of TB patients cared for by private medical providers and other providers outside HDs (PMPs). We sought to determine whether there were differences in care provided by HDs and PMPs to inform public health planning under the ACA.

Methods

We conducted a retrospective, cross-sectional analysis of California TB registry data. We included adult TB patients with culture-positive, pulmonary TB reported in California during 2007–2011. We examined trends, described case characteristics, and created multivariate models measuring two standards of TB care in PMP- and HD-managed patients: documented culture conversion within 60 days, and use of directly observed therapy (DOT).

Results

The proportion of PMP-managed TB patients increased during 2007–2011 (p = 0.002). On univariable analysis (N = 4,606), older age, white, black or Asian/Pacific Islander race, and birth in the United States were significantly associated with PMP care (p<0.05). Younger age, Hispanic ethnicity, homelessness, drug or alcohol use, and cavitary and/or smear-positive TB disease, were associated with HD care. Multivariable analysis showed PMP care was associated with lack of documented culture conversion (adjusted relative risk [aRR] = 1.37, confidence interval [CI] 1.25–1.51) and lack of DOT (aRR = 8.56, CI 6.59–11.1).

Conclusion

While HDs cared for TB cases with more social and clinical complexities, patients under PMP care were less likely to receive DOT and have documented culture conversion. This indicates a need for close collaboration between PMPs and HDs to ensure that optimal care is provided to all TB patients and TB transmission is halted. Strategies to enhance collaboration between HDs and PMPs should be included in ACA implementation.     

Effect of diet composition on feeding,digestion, and reproduction in Glossina morsitans

Quantitative estimates of food intake by adult female Glossina morsitans were made using ⁴⁵Ca in the diet. Rate of digestion was measured by estimating residual nitrogen in the gut contents at various intervals after feeding. Results show that the superiority of pig blood over cow blood as a diet for in vitro feeding of Glossina cannot be explained in terms of quantities ingested or in terms of digestion rate by the fly. Comparing blood from a number of mammalian hosts, only that of pig elicited production of optimal sized offspring and no correlation could be found between haemoglobin content or trypsin inhibition capacity and offspring size for any of the bloods tested. An exchange of protein fractions between pig and cow blood failed to demonstrate a specific component of pig blood which accounts for its nutritional superiority. Removal of serum, and suspension of washed pig erythrocytes in a saline solution resulted in production of very small offspring. However, the addition of physiological concentrations of soluble albumen to such a suspension produced an improvement in both fecundity and offspring size. Feeding on serum alone or upon serum containing added albumen in solution resulted in poor survival and fecundity was reduced to zero. Results emphasize the importance of both serum and erythrocyte components of blood in providing an optimal diet for Glossina.     

Immunoregulatory role of Ig isotypes. I. Induction of contrasuppressor T cells for contact sensitivity responses by antibodies of the IgM, IgG1, and IgG3 isotypes

A profound state of specific tolerance for the contact sensitivity reaction can be produced by i.v. exposure to hapten on the surface of syngeneic macrophages. When the same haptenated cells are incubated with specific antibody to form cell-bound Ag-antibody complexes, i.v. injection induces immunity rather than tolerance. We observe that such cell-bound Ag-antibody complexes induce not only effector cells for contact sensitivity but also hapten-specific contrasuppressor T (Tcs) cells, which are capable of rendering effector cells resistant to the inhibitory effects of Ts cells. Whereas the induction of the effector cells of contact sensitivity by cell-bound complexes required I region compatibility between the injected cells and the recipient, the induction of Tcs cells showed no genetic restriction. On the other hand, induction of contrasuppression required intact Fc on the complexed antibody, inasmuch as F(ab')2 fragments of specific antibody did not induce immunity. In addition, Tcs cells could also be induced by Ag-antibody complexes on opsonized TNP-mouse RBC treated with anti-TNP antibody. Immunity induced by cell-bound Ag-antibody complexes was observed only when antibodies of the IgM, IgG3, or IgG1 isotypes are used to generate the complexes. Further studies demonstrated that the Tcs cells induced in this way displayed the phenotype of Tcs cells described in other systems (Lyt-1+,2- I-J+, Vicia villosa lectin-adherent) and released a hapten-specific contrasuppressor factor. These studies indicate that Tcs cells can be induced independently of other T cells (such as the effector cells of contact sensitivity) and are likely to be responsible for some of the immunoregulatory effects of cell-bound Ag-antibody complexes. The role of antibody isotype in the induction of Tcs cells is discussed.