Adaptive Evolution of Toll-Like Receptors (TLRs) in the Family Suidae

Members of the family Suidae have diverged over extended evolutionary periods in diverse environments, suggesting that adaptation in response to endemic infectious agents may have occurred. Toll-like receptors (TLRs) comprise a multigene family that acts as the first line of defense against infectious microbes at the host-environment interface. We hypothesized that across the Suidae, positive selection mediated by infectious agents has contributed to the evolution of TLR diversity. Thus, we analyzed Sus scrofa, Sus barbatus, Sus verrucosus, Sus celebensis, Sus scebifrons, Babyrousa babyrussa, Potamochoerus larvatus, Potamochoerus porcus and Phacochoerus africanus genomes. Specifically, analyses were performed to identify evidence of positive selection using Maximum likelihood (ML) methods within a phylogenetic framework for bacterial and viral sensing Suidae TLR extracellular domains. Our analyses did not reveal evidence of positive selection for TLR3 and TLR7, suggesting strong functional conservation among these two genes for members of the Suidae. Positive selection was inferred for Suidae TLR1, TLR2, TLR6 and TLR8 evolution. ML methods identified amino acid sites of the bacterial sensing TLR1, TLR2, TLR6 and the viral sensing TLR8 to be under persistent positive selection. Some of these sites are in close proximity to functionally relevant sites, further strengthening the case for pathogen mediated selection for these sites. The branch leading to the genus Sus demonstrated evidence of episodic positive selection for TLR1, indicating selection mediated by infectious agents encountered within the specific geographic origin of the Sus. These results indicate that species of the Suidae have positively selected residues within functional domains of TLRs reflective of prior infections. Thus, TLR genes represent candidates for experimental validation to determine their functional role in antibacterial and antiviral activity within members of the Suidae.     

Determination of Sex from Footprint Dimensions in a Ghanaian Population

The present study sought to verify the utility and reliability of footprint dimensions in sex determination in a Ghanaian population. Bilateral footprints were obtained from 126 Ghanaian students (66 males and 60 females) aged 18–30 years at Koforidua Polytechnic using an ink pad and white papers. Seven dimensions–length of each toe (designated T1-T5) from the most anterior point of the toe to the mid-rear heel point, breadth at ball (BAB) and breadth at heel (BAH)–and the heel-ball (HB) index were obtained from each footprint. Some footprint dimensions (i.e. T2, T3, T4 and T5) showed statistically significant bilateral asymmetry in males only. All the footprint dimensions, except HB index, were significantly greater in males than females (p<0.001). Applied singly in discriminant function analysis, the footprint dimensions allowed 69.8%-80.3% of cases to be correctly classified into their sex groups; the accuracy of sex classification was higher using left footprints than right footprints. With all dimensions subjected to stepwise discriminant function analysis 80.3% and 77% of cases could be correctly classified, combining both T5 and BAH for left footprints and T1, BAB and BAH for left footprints respectively. The present study has demonstrated, for the first time among Ghanaian subjects, the utility and reliability of sex determination standards developed from footprint dimensions. The results thus provide the baseline for elaborated studies in the future.     

Silencing of PTK7 in colon cancer cells: caspase-10-dependent apoptosis via mitochondrial pathway

Protein tyrosine kinase-7 (PTK7) is a catalytically inactive receptor tyrosine kinase (RTK). PTK7 is upregulated in many common human cancers, including colon cancer, lung cancer, gastric cancer and acute myeloid leukemia. The reason for this up-regulation is not yet known. To explore the functional role of PTK7, the expression of PTK7 in HCT 116 cells was examined using small interference (siRNA)-mediated gene silencing. Following transfection, the siRNA successfully suppressed PTK7 mRNA and protein expression. Knocking down of PTK7 in HCT 116 cells inhibited cell proliferation compared to control groups and induced apoptosis. Furthermore, this apoptosis was characterized by decreased mitochondrial membrane potential and activation of caspase-9 and -10. Addition of a caspase-10 inhibitor totally blocked this apoptosis, suggesting that caspase-10 may play a critical role in PTK7-knockdown-induced apoptosis, downstream of mitochondria. These observations may indicate a role for PTK7 in cell proliferation and cell apoptosis and may provide a potential therapeutic pathway for the treatment of a variety of cancers.     

Reprint of "MDCK cell permeability characteristics of a sulfenamide produg: strategic implications in considering sulfenamide prodrugs for oral delivery of NH acids" [Bioorg. Med. Chem. Lett. 21 (2011) 172-175

The objective of this Letter is both to report the permeability results of a linezolid-based sulfenamide prodrug in an MDCK cell model (enterocyte surrogate system) and to discuss the strategic implications of these results for considering sulfenamide prodrugs to enhance the oral delivery of weakly acidic NH-acids (e.g., amides, ureas, etc.). The two main findings from this study are that the sulfenamide prodrug does not appear to survive intracellular transport due to conversion to linezolid and that there appears to be an apically-oriented surface conversion pathway that can additionally serve to convert the sulfenamide prodrug to linezolid upon approach of the apical membrane. It is hoped that these findings, along with the discussion of the strategic implications, will facilitate a greater awareness of the potential strengths and weaknesses inherent in the sulfenamide prodrug approach for enhancing the oral delivery of weakly acidic NH-acid drugs.     

Distribution and abundance of forest birds in Ghana

Ntiamoa-Baidu, Y., Owusu, E.H., Asamoah, S. & Owusu-Boateng, K. 2000. Distribution and abundance of forest birds in Ghana. Ostrich 71 (1 & 2): 262–268.

Forest reserves within the Ghanaian rain forest have been classified into categories (Condition I-VI) on the basis of their botanical importance and status of the vegetation. We present data on the distribution and abundance of avifauna of 28 Condition II and III forest reserves in southern Ghana based on line transect counts and mist-net captures. A total of 227 species were recorded for all the sites; species records for individual sites ranged from 78–119. The dominant groups in the overall survey were Muscicapidae (represented by 40 species), Pcynonotidae (21) and Cuculidae (12). The most abundant bird species in the Ghanaian forests were Yellow-whiskered Greenbul, Green Hylia, Green Pigeon and Olive Sunbird. Species encounter rates ranged from 16.7 to 50.7 species per km with individual bird encounter rates of 27.9 to 172.0 birds per km. Capture rates in mist-nets ranged from 1.2 to 3.9 birds per 100 metre net-hr (mnh). A total of 183 species were recorded in Condition II forest as compared with 167 in Condition III forests. The effects of forest condition and vegetation types on the total number of species recorded were, however, not statistically significant. The Similarity Index for bird communities within Condition II and III forests was 0.72. Bird species composition in the two forest types also differed: e.g., seven primary forest species, as well as 40% of the species associated with primary and matured secondary forest which were recorded in Condition II forests, were absent from Condition III forests. Bird communities of Moist Evergreen, Upland Evergreen and Moist semi-Deciduous were more similar than communities in the Wet Evergreen forest type. The implication of the results for conservation of the Ghana's forests is discussed.     

Risk factors associated with positive QuantiFERON-TB Gold In-Tube and tuberculin skin tests results in Zambia and South Africa

Introduction

The utility of T-cell based interferon-gamma release assays for the diagnosis of latent tuberculosis infection remains unclear in settings with a high burden of tuberculosis.

Objectives

To determine risk factors associated with positive QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) results and the level of agreement between the tests; to explore the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST.

Methods

Adult household contacts of tuberculosis patients were invited to participate in a cross-sectional study across 24 communities in Zambia and South Africa. HIV, QFT-GIT and TST tests were done. A questionnaire was used to assess risk factors.

Results

A total of 2,220 contacts were seen. 1,803 individuals had interpretable results for both tests, 1,147 (63.6%) were QFT-GIT positive while 725 (40.2%) were TST positive. Agreement between the tests was low (kappa = 0.24). QFT-GIT and TST results were associated with increasing age (adjusted OR [aOR] for each 10 year increase for QFT-GIT 1.15; 95% CI: 1.06–1.25, and for TST aOR: 1.10; 95% CI 1.01–1.20). HIV positivity was less common among those with positive results on QFT-GIT (aOR: 0.51; 95% CI: 0.39–0.67) and TST (aOR: 0.61; 95% CI: 0.46–0.82). Smear positivity of the index case was associated with QFT-GIT (aOR: 1.25; 95% CI: 0.90–1.74) and TST (aOR: 1.39; 95% CI: 0.98–1.98) results. We found little evidence in our data to support our hypotheses.

Conclusion

QFT-GIT may not be more sensitive than the TST to detect risk factors associated with tuberculous infection. We found little evidence to support the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST.     

Long-term neuroprotection from a potent redox-modulating metalloporphyrin in the rat

Sustained oxidative stress is a known sequel to focal cerebral ischemia. This study examined the effects of treatment with a single dose or sustained infusion of the redox-modulating MnPorphyrin Mn^IIITDE-2-ImP⁵⁺ on outcome from middle cerebral artery occlusion (MCAO) in the rat. Normothermic rats were subjected to 90 min MCAO followed by 90 min reperfusion and then were treated with a single intracerebroventricular dose of Mn^IIITDE-2-ImP⁵⁺. Neurologic and histologic outcomes were assessed at 1 or 8 weeks postischemia. A single dose of Mn^IIITDE-2-ImP⁵⁺ caused a dose-dependent improvement in histologic and neurologic outcome when assessed 1 week postischemia. Mn^IIITDE-2-ImP⁵⁺ afforded preservation of brain aconitase activity at 5.5 h after reperfusion onset, consistent with its known antioxidant properties. Mn^IIITDE-2-ImP⁵⁺ also attenuated postischemic NF-κB activation. Evidence for effects on cerebral infarct size and neurologic function had completely dissipated when rats were allowed to survive for 8 weeks postischemia. In contrast, a 1-week continuous intracerebroventricular Mn^IIITDE-2-ImP⁵⁺ infusion caused persistent and substantive reduction in both cerebral infarct size and neurologic deficit at 8 weeks postischemia. Pharmacologic modulation of postischemic oxidative stress is likely to require sustained intervention for enduring efficacy in improving neurologic and histologic outcome from a transient focal ischemic insult.     

Listening to Women's Voices: The Quality of Care of Women Experiencing Severe Maternal Morbidity, in Accra, Ghana

Background

Women who survive severe obstetric complications can provide insight into risk factors and potential strategies for prevention of maternal morbidity as well as maternal mortality. We interviewed 32 women, in an urban facility in Ghana, who had experienced severe morbidity defined using a standardized WHO near-miss definition and identification criteria. Women provided personal accounts of their experiences of severe maternal morbidity and perceptions of the care they received.

Methods and Findings

The study took place in a referral facility in urban Accra, and semi-structured interviews were conducted with women who had either a maternal near miss (n = 17) or a potentially life-threatening complication (n = 15). The most common themes surrounding the traumatic delivery were the fear of dying and concern over the potential (or actual) loss of the baby. For many women, the loss of a baby negatively influenced how they viewed and coped with this experience. Women’s perceptions of the quality of the care highlighted several key factors such as the importance of information, good communication and attitudes, and availability of human (i.e., more doctors) and physical resources (i.e., more beds, water) at the facility.

Conclusions

Our results suggest that experiences of women with severe maternal morbidity may inform different aspects of quality improvement in the facilities, which in turn have a positive impact on future health seeking behavior, service utilization and reduction in maternal morbidity and mortality.