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.     

Novel lap test determines the mechanics of delamination between annular lamellae of the intervertebral disc

Delamination between lamellae of the annulus fibrosus is a crucial stage of intervertebral disc herniation, and to better understand the mechanics of the delamination process, a novel lap test was devised. Specimens consisting of two adjacent, naturally bonded lamellae were obtained from the cervical region of frozen porcine spines. They were cut into specimens nominally 3.5 mm wide by 7 mm long and tabs of the deep and superficial layers were removed from opposite ends of the specimens so that a 4.5–5.0 mm long intact interface remained between the lamellae. Specimens were mounted in a BioTester tensile instrument using BioRake attachments having 5 sharpened points side-by-side, and they were strained at 2%/s. Force–time curves were obtained and, using tracking software, a detailed map was made of the time course of the displacements within the specimens. Extensibility of the lamellae themselves was found to substantially complicate interpretation of the data. The experiments, together with mathematical analyses and finite element models, show that much of the shear load is transferred between lamellae at the ends of the bonded region, a finding of clinical importance. The inter-lamellae bond was found to have a peak strength of 0.30±0.05 N/mm of specimen width (not to be confused with lap length), and the remarkable ability to carry substantial load even when lamellae had displaced up to 10 mm relative to each other.     

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.     

Deploying aptameric sensing technology for rapid pandemic monitoring

The genome of virulent strains may possess the ability to mutate by means of antigenic shift and/or antigenic drift as well as being resistant to antibiotics with time. The outbreak and spread of these virulent diseases including avian influenza (H1N1), severe acute respiratory syndrome (SARS-Corona virus), cholera (Vibrio cholera), tuberculosis (Mycobacterium tuberculosis), Ebola hemorrhagic fever (Ebola Virus) and AIDS (HIV-1) necessitate urgent attention to develop diagnostic protocols and assays for rapid detection and screening. Rapid and accurate detection of first cases with certainty will contribute significantly in preventing disease transmission and escalation to pandemic levels. As a result, there is a need to develop technologies that can meet the heavy demand of an all-embedded, inexpensive, specific and fast biosensing for the detection and screening of pathogens in active or latent forms to offer quick diagnosis and early treatments in order to avoid disease aggravation and unnecessary late treatment costs. Nucleic acid aptamers are short, single-stranded RNA or DNA sequences that can selectively bind to specific cellular and biomolecular targets. Aptamers, as new-age bioaffinity probes, have the necessary biophysical characteristics for improved pathogen detection. This article seeks to review global pandemic situations in relation to advances in pathogen detection systems. It particularly discusses aptameric biosensing and establishes application opportunities for effective pandemic monitoring. Insights into the application of continuous polymeric supports as the synthetic base for aptamer coupling to provide the needed convective mass transport for rapid screening is also presented.     

Temporal Patterns of Diversification across Global Cichlid Biodiversity (Acanthomorpha: Cichlidae)

The contrasting distribution of species diversity across the major lineages of cichlids makes them an ideal group for investigating macroevolutionary processes. In this study, we investigate whether different rates of diversification may explain the disparity in species richness across cichlid lineages globally. We present the most taxonomically robust time-calibrated hypothesis of cichlid evolutionary relationships to date. We then utilize this temporal framework to investigate whether both species-rich and depauperate lineages are associated with rapid shifts in diversification rates and if exceptional species richness can be explained by clade age alone. A single significant rapid rate shift increase is detected within the evolutionary history of the African subfamily Pseudocrenilabrinae, which includes the haplochromins of the East African Great Lakes. Several lineages from the subfamilies Pseudocrenilabrinae (Australotilapiini, Oreochromini) and Cichlinae (Heroini) exhibit exceptional species richness given their clade age, a net rate of diversification, and relative rates of extinction, indicating that clade age alone is not a sufficient explanation for their increased diversity. Our results indicate that the Neotropical Cichlinae includes lineages that have not experienced a significant rapid burst in diversification when compared to certain African lineages (rift lake). Neotropical cichlids have remained comparatively understudied with regard to macroevolutionary patterns relative to African lineages, and our results indicate that of Neotropical lineages, the tribe Heroini may have an elevated rate of diversification in contrast to other Neotropical cichlids. These findings provide insight into our understanding of the diversification patterns across taxonomically disparate lineages in this diverse clade of freshwater fishes and one of the most species-rich families of vertebrates.     

The Bioavailability of Lead in Mining Wastes: Physical/Chemical Considerations

Abstract

In this paper we review the physiological and geochemical factors affecting lead bioavailability, and particularly, the unique physical/chemical properties of lead derived from mining wastes based on both theory and empirical observations. The relationship between blood lead levels and soil lead concentrations derived from epidemiological studies indicates that lead in soil from mining sites appears to have less of an effect on blood lead levels in children than does lead at urban sites or sites with an active lead smelter. Differences in bioavailability of various lead species offers a plausible explanation for the relative differences in their impact on blood lead. In this paper, we evaluate from a physiological viewpoint aqueous solubility, absorption/desorption processes, and uptake mechanisms that may control lead bioavailability within the Gl tract. A number of these processes, including the role of passive diffusion, competition with calcium for a common transport mechanism, and the role of organic ligands, are discussed. Geochemical processes that relate to lead bioavailability in the Gl tract are also considered. Galena (PbS) and its alteration product, anglesite (PbSO⁴), are the primary forms of lead associated with mining wastes. Equilibrium thermodynamics and dissolution kinetics of PbSO⁴ are modeled because this solid is likely to control the concentration of dissolved lead from many mine wastes in the Gl tract. The geochemical models DIASTAB and MINTEAQ2 are used to calculate theoretical estimates of lead dissolution and a model is proposed to evaluate lead bioavailability by laboratory methods taking into account both kinetic and equilibrium considerations. This type of model requires calibration with animal toxicological studies of lead bioavailability and with epidemiological studies of different types of lead sites. Ultimately, such a geochemical model could be used to evaluate the potential for public health impacts from a particular type of lead in soil.     

Joint Genome-Wide Profiling of miRNA and mRNA Expression in Alzheimer's Disease Cortex Reveals Altered miRNA Regulation

Although microRNAs are being extensively studied for their involvement in cancer and development, little is known about their roles in Alzheimer''s disease (AD). In this study, we used microarrays for the first joint profiling and analysis of miRNAs and mRNAs expression in brain cortex from AD and age-matched control subjects. These data provided the unique opportunity to study the relationship between miRNA and mRNA expression in normal and AD brains. Using a non-parametric analysis, we showed that the levels of many miRNAs can be either positively or negatively correlated with those of their target mRNAs. Comparative analysis with independent cancer datasets showed that such miRNA-mRNA expression correlations are not static, but rather context-dependent. Subsequently, we identified a large set of miRNA-mRNA associations that are changed in AD versus control, highlighting AD-specific changes in the miRNA regulatory system. Our results demonstrate a robust relationship between the levels of miRNAs and those of their targets in the brain. This has implications in the study of the molecular pathology of AD, as well as miRNA biology in general.