Musculoskeletal modelling of the Nile crocodile (Crocodylus niloticus) hindlimb: Effects of limb posture on leverage during terrestrial locomotion

We developed a three-dimensional, computational biomechanical model of a juvenile Nile crocodile (Crocodylus niloticus) pelvis and hindlimb, composed of 47 pelvic limb muscles, to investigate muscle function. We tested whether crocodiles, which are known to use a variety of limb postures during movement, use limb orientations (joint angles) that optimise the moment arms (leverages) or moment-generating capacities of their muscles during different limb postures ranging from a high walk to a sprawling motion. We also describe the three-dimensional (3D) kinematics of the crocodylian hindlimb during terrestrial locomotion across an instrumented walkway and a treadmill captured via X-ray Reconstruction of Moving Morphology (biplanar fluoroscopy; ‘XROMM’). We reconstructed the 3D positions and orientations of each of the hindlimb bones and used dissection data for muscle lines of action to reconstruct a focal, subject-specific 3D musculoskeletal model. Motion data for different styles of walking (a high, crouched, bended and two types of sprawling motion) were fed into the 3D model to identify whether any joints adopted near-optimal poses for leverage across each of the behaviours. We found that (1) the hip adductors and knee extensors had their largest leverages during sprawling postures and (2) more erect postures typically involved greater peak moment arms about the hip (flexion-extension), knee (flexion) and metatarsophalangeal (flexion) joints. The results did not fully support the hypothesis that optimal poses are present during different locomotory behaviours because the peak capacities were not always reached around mid-stance phase. Furthermore, we obtained few clear trends for isometric moment-generating capacities. Therefore, perhaps peak muscular leverage in Nile crocodiles is instead reached either in early/late stance or possibly during swing phase or other locomotory behaviours that were not studied here, such as non-terrestrial movement. Alternatively, our findings could reflect a trade-off between having to execute different postures, meaning that hindlimb muscle leverage is not optimised for any singular posture or behaviour. Our model, however, provides a comprehensive set of 3D estimates of muscle actions in extant crocodiles which can form a basis for investigating muscle function in extinct archosaurs

The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

1H-NMR-Based Metabolomic Profiling of CSF in Early Amyotrophic Lateral Sclerosis

Background: Pathophysiological mechanisms involved in amyotrophic lateral sclerosis (ALS) are complex and none has identified reliable markers useful in routine patient evaluation. The aim of this study was to analyze the CSF of patients with ALS by 1 H NMR (Nuclear Magnetic Resonance) spectroscopy in order to identify biomarkers in the early stages of the disease, and to evaluate the biochemical factors involved in ALS. Methodology: CSF samples were collected from patients with ALS at the time of diagnosis and from patients without neurodegenerative diseases. One and two-dimensional 1 H NMR analyses were performed and metabolites were quantified by the ERETIC method. We compared the concentrations of CSF metabolites between both groups. Finally, we performed principal component (PCA) and discriminant analyses. Principal Findings: Fifty CSF samples from ALS patients and 44 from controls were analyzed. We quantified 17 metabolites including amino-acids, organic acids, and ketone bodies. Quantitative analysis revealed significantly lower acetate concentrations (p = 0.0002) in ALS patients compared to controls. Concentration of acetone trended higher (p = 0.015), and those of pyruvate (p = 0.002) and ascorbate (p = 0.003) were higher in the ALS group. PCA demonstrated that the pattern of analyzed metabolites discriminated between groups. Discriminant analysis using an algorithm of 17 metabolites reveale

Genetic susceptibility of intervertebral disc degeneration among young Finnish adults

<p>Abstract</p> <p>Background</p> <p>Disc degeneration (DD) is a common condition that progresses with aging. Although the events leading to DD are not well understood, a significant genetic influence has been found. This study was undertaken to assess the association between relevant candidate gene polymorphisms and moderate DD in a well-defined and characterized cohort of young adults. Focusing on young age can be valuable in determining genetic predisposition to DD.</p> <p>Methods</p> <p>We investigated the associations of existing candidate genes for DD among 538 young adults with a mean age of 19 belonging to the 1986 Northern Finland Birth Cohort. Nineteen single nucleotide polymorphisms (SNP) in 16 genes were genotyped. We evaluated lumbar DD using the modified Pfirrmann classification and a 1.5-T magnetic resonance scanner for imaging.</p> <p>Results</p> <p>Of the 538 individuals studied, 46% had no degeneration, while 54% had DD and 51% of these had moderate DD. The risk of DD was significantly higher in subjects with an allele G of <it>IL6 </it>SNPs rs1800795 (OR 1.45, 95% CI 1.07-1.96) and rs1800797 (OR 1.37, 95% CI 1.02-1.85) in the additive inheritance model. The role of <it>IL6 </it>was further supported by the haplotype analysis, which resulted in an association between the GGG haplotype (SNPs rs1800797, rs1800796 and rs1800795) and DD with an OR of 1.51 (95% CI 1.11-2.04). In addition, we observed an association between DD and two other polymorphisms, <it>SKT </it>rs16924573 (OR 0.27 95% CI 0.07-0.96) and <it>CILP </it>rs2073711 in women (OR 2.04, 95% CI 1.07-3.89).</p> <p>Conclusion</p> <p>Our results indicate that <it>IL6</it>, <it>SKT </it>and <it>CILP </it>are involved in the etiology of DD among young adults.</p

Metarhodopsin control by arrestin, light-filtering screening pigments, and visual pigment turnover in invertebrate microvillar photoreceptors

The visual pigments of most invertebrate photoreceptors have two thermostable photo-interconvertible states, the ground state rhodopsin and photo-activated metarhodopsin, which triggers the phototransduction cascade until it binds arrestin. The ratio of the two states in photoequilibrium is determined by their absorbance spectra and the effective spectral distribution of illumination. Calculations indicate that metarhodopsin levels in fly photoreceptors are maintained below ~35% in normal diurnal environments, due to the combination of a blue-green rhodopsin, an orange-absorbing metarhodopsin and red transparent screening pigments. Slow metarhodopsin degradation and rhodopsin regeneration processes further subserve visual pigment maintenance. In most insect eyes, where the majority of photoreceptors have green-absorbing rhodopsins and blue-absorbing metarhodopsins, natural illuminants are predicted to create metarhodopsin levels greater than 60% at high intensities. However, fast metarhodopsin decay and rhodopsin regeneration also play an important role in controlling metarhodopsin in green receptors, resulting in a high rhodopsin content at low light intensities and a reduced overall visual pigment content in bright light. A simple model for the visual pigment–arrestin cycle is used to illustrate the dependence of the visual pigment population states on light intensity, arrestin levels and pigment turnover

‘Gatekeepers’ of Islamic financial circuits: Analysing urban geographies of the global Shari’a elite

This paper analyses the importance of 'Shari'a scholars' in the Islamic Financial Services (IFS) sector, which has been a growing global practice since the 1970s. Based on Shari'a Law, IFS firms provide banking, finance and insurance respecting faith-based prohibitions on interest, speculation and risk taking. Although IFS firms operate across a variety of scales and involve a range of actors, this paper focuses on the transnational capacities of Shari'a experts employed by IFS firms. These scholars use their extensive knowledge of Shari'a Law to assess the 'Islamic' character of a firm's operations, and assist the development of Shari'a-compliant products. As they embody necessary entry-points into Islamic circuits of knowledge and authority, members of what we dub the 'global Shari'a elite' can be regarded as 'gatekeepers' of Islamic financial circuits. Drawing on a comprehensive data source we present a geographical analysis of Shari'a board membership, nationality and educational background of 253 Shari'a scholars. The results show that the global Shari'a elite connects a limited number of IFS hubs (e. g. Dubai, Kuala Lumpur, Kuwait City, Manama, and London) to knowledge and authority networks falling outside 'mainstream' business and service spheres

Strength of Hydrogen Bond Network Takes Crucial Roles in the Dissociation Process of Inhibitors from the HIV-1 Protease Binding Pocket

To understand the underlying mechanisms of significant differences in dissociation rate constant among different inhibitors for HIV-1 protease, we performed steered molecular dynamics (SMD) simulations to analyze the entire dissociation processes of inhibitors from the binding pocket of protease at atomistic details. We found that the strength of hydrogen bond network between inhibitor and the protease takes crucial roles in the dissociation process. We showed that the hydrogen bond network in the cyclic urea inhibitors AHA001/XK263 is less stable than that of the approved inhibitor ABT538 because of their large differences in the structures of the networks. In the cyclic urea inhibitor bound complex, the hydrogen bonds often distribute at the flap tips and the active site. In contrast, there are additional accessorial hydrogen bonds formed at the lateral sides of the flaps and the active site in the ABT538 bound complex, which take crucial roles in stabilizing the hydrogen bond network. In addition, the water molecule W301 also plays important roles in stabilizing the hydrogen bond network through its flexible movement by acting as a collision buffer and helping the rebinding of hydrogen bonds at the flap tips. Because of its high stability, the hydrogen bond network of ABT538 complex can work together with the hydrophobic clusters to resist the dissociation, resulting in much lower dissociation rate constant than those of cyclic urea inhibitor complexes. This study may provide useful guidelines for design of novel potent inhibitors with optimized interactions