Further consideration of the curvature of the Neandertal Femur.

OBJECTIVES: Neandertal femora are particularly known for having a marked sagittal femoral curvature. This study examined femoral curvature in Neandertals in comparison to a modern human population from Belgium by the use of three-dimensional (3D) quadric surfaces modeled from the bone surface. 3D models provide detailed information and enabled femoral curvature to be analyzed in conjunction with other morphological parameters. MATERIALS AND METHODS: 3D models were created from CT scans of 75 modern human femora and 7 Neandertal femora. Quadric surfaces (QS) were created from the triangulated surface vertices in all areas of interest (neck, head, diaphyseal shaft, condyles) extracted from previously placed anatomical landmarks. The diaphyseal shaft was divided into five QS shapes and curvature was measured by degrees of difference between QS shapes. Each bone was placed in a local coordinate system enabling each bone to be analyzed in the same way. RESULTS: The use of 3D quadric surface fitting allowed the distribution of curvature with similarly curved femora to be analyzed and the different patterns of curvature between the two groups to be determined. The Neandertals were shown to have a higher degree of femoral curvature and a more distal point of femoral curvature than the modern human population from Belgium. CONCLUSIONS: Morphological aspects of the Neandertal femur are different from this modern human population although mainly seem unrelated to femoral curvature. The relative lack of correlations with other femoral bony morphological factors suggests femoral curvature variations may be related to other aspects.

How different are the Kebara 2 ribs to modern humans?

This study analyses rib geometric parameters of individual ribs of 14 modern human subjects (7 males and 7 females) in comparison to the reconstructed ribs of the Kebara 2 skeleton which was taken from the reconstruction of a Neandertal thorax by Sawyer & Maley (2005). Three-dimensional (3D) models were segmented from CT scans and each rib vertex cloud was placed into a local coordinate system defined from the rib principal axes. Rib clouds were then analysed using best fitting ellipses of the external contours of the cross-section areas. The centroid of each ellipse was then used to measure the centroidal pathway between each slice (rib midline). Curvature of the ribs was measured from the mid-line of the ribs as the sum of angles between successive centroids in adjacent cross sections. Distinct common patterns were noted in all rib geometric parameters for modern humans. The Kebara 2 reconstructed ribs also followed the same patterns. This study demonstrated that there are differences between the sexes in rib geometrical parameters, with females showing smaller rib width, chord length and arc length, but greater curvature (rib torsion, rib axial curvature, rib anterior-posterior bending) than males. The Kebara 2 reconstructed ribs were within the modern human range for the majority of geometrical parameters.

Femoral curvature variability in modern humans using three-dimensional quadric surface fitting.

INTRODUCTION: This study analysed femoral curvature in a population from Belgium in conjunction with other morphological characteristics by the use of three-dimensional (3D) quadric surfaces (QS) modelled from the bone surface. METHODS: 3D models were created from computed tomography data of 75 femoral modern human bones. Anatomical landmarks (ALs) were palpated in specific bony areas of the femur (shaft, condyles, neck and head). QS were then created from the surface vertices which enclose these ALs. The diaphyseal shaft was divided into five QS shapes to analyse curvature in different parts of the shaft. RESULTS: Femoral bending differs in different parts of the diaphyseal shaft. The greatest degree of curvature was found in the distal shaft (mean 4.5° range 0.2°-10°) followed by the proximal (mean 4.4° range 1.5°-10.2°), proximal intermediate (mean 3.7° range 0.9°-7.9°) and distal intermediate (mean 1.8° range 0.2°-5.6°) shaft sections. The proximal and distal angles were significantly more bowed than the intermediate proximal and the intermediate distal angle. There was no significant difference between the proximal and distal angle. No significant correlations were found between morphological characteristics and femoral curvature. An extremely large variability of femoral curvature with several bones displaying very high or low degrees of femoral curvature was also found. CONCLUSION: 3D QS fitting enables the creation of accurate models which can discriminate between different patterns in similar curvatures and demonstrates there is a clear difference between curvature in different parts of the shaft.

Sex determination using the Probabilistic Sex Diagnosis (DSP: Diagnose Sexuelle Probabiliste) tool in a virtual environment.

The hip bone is one of the most reliable indicators of sex in the human body due to the fact it is the most dimorphic bone. Probabilistic Sex Diagnosis (DSP: Diagnose Sexuelle Probabiliste) developed by Murail et al., in 2005, is a sex determination method based on a worldwide hip bone metrical database. Sex is determined by comparing specific measurements taken from each specimen using sliding callipers and computing the probability of specimens being female or male. In forensic science it is sometimes not possible to sex a body due to corpse decay or injury. Skeletalization and dissection of a body is a laborious process and desecrates the body. There were two aims to this study. The first aim was to examine the accuracy of the DSP method in comparison with a current visual sexing method on sex determination. A further aim was to see if it was possible to virtually utilise the DSP method on both the hip bone and the pelvic girdle in order to utilise this method for forensic sciences. For the first part of the study, forty-nine dry hip bones of unknown sex were obtained from the Body Donation Programme of the Université Libre de Bruxelles (ULB). A comparison was made between DSP analysis and visual sexing on dry bone by two researchers. CT scans of bones were then analysed to obtain three-dimensional (3D) virtual models and the method of DSP was analysed virtually by importing the models into a customised software programme called lhpFusionBox which was developed at ULB. The software enables DSP distances to be measured via virtually-palpated bony landmarks. There was found to be 100% agreement of sex between the manual and virtual DSP method. The second part of the study aimed to further validate the method by analysing thirty-nine supplementary pelvic girdles of known sex blind. There was found to be a 100% accuracy rate further demonstrating that the virtual DSP method is robust. Statistically significant differences were found in the identification of sex between researchers in the visual sexing method although both researchers identified the same sex in all cases in the manual and virtual DSP methods for both the hip bones and pelvic girdles.

[Application of the musculo-skeletal modelling software lhpFusionBox to a paleoanthropological problem: the Spyrou Neandertal moves!]. / Application du logiciel de modélisation musculo-squelettique lhpFusionBox à une problématique paléo-anthropologique - Spyrou le Néandertalien marche !

LhpFusionBox is a program originally designed for biomechanical and clinical studies relating to the musculoskeletal system of anatomically modern humans (AMH). The program has recently been adapted for paleontological purposes and used to reconstruct and biomechanically analyse a fossil hominid. There is no complete Neandertal skeleton in the fossil record. The aim of the study was to reconstruct a complete three-dimensional (3D) model of a Neandertal using the relatively complete Spy II Neandertal and to conduct biomechanical feasibility studies on the knee and hamstring moment arms of the skeleton. Different Neandertal specimens were scaled to the size of Spy II to replace incomplete or missing bones. Biomechanical feasibility studies performed on the knee seem to show that Neandertal and AMHh gait is similar and Neandertals were shown to have larger moment arms in the hamstring muscles, which would have given them a mechanical advantage. The complete Neandertal was printed in 3D and used as the base to create the artistic model of "Spyrou" housed at l'Espace de l'Homme de Spy (EHoS) museum.

A vision and strategy for the virtual physiological human: 2012 update.

European funding under Framework 7 (FP7) for the virtual physiological human (VPH) project has been in place now for 5 years. The VPH Network of Excellence (NoE) has been set up to help develop common standards, open source software, freely accessible data and model repositories, and various training and dissemination activities for the project. It is also working to coordinate the many clinically targeted projects that have been funded under the FP7 calls. An initial vision for the VPH was defined by the FP6 STEP project in 2006. In 2010, we wrote an assessment of the accomplishments of the first two years of the VPH in which we considered the biomedical science, healthcare and information and communications technology challenges facing the project (Hunter et al. 2010 Phil. Trans. R. Soc. A 368, 2595-2614 (doi:10.1098/rsta.2010.0048)). We proposed that a not-for-profit professional umbrella organization, the VPH Institute, should be established as a means of sustaining the VPH vision beyond the time-frame of the NoE. Here, we update and extend this assessment and in particular address the following issues raised in response to Hunter et al.: (i) a vision for the VPH updated in the light of progress made so far, (ii) biomedical science and healthcare challenges that the VPH initiative can address while also providing innovation opportunities for the European industry, and (iii) external changes needed in regulatory policy and business models to realize the full potential that the VPH has to offer to industry, clinics and society generally.

The dangers of multi-male groupings: trauma and healing in cercopithecoid monkeys from Cameroon.

This study examines the potential linkage between social organization and trauma in a sample of cercopithecids from Cameroon. Skeletal trauma is described in a museum collection of eight sympatric monkey species. Macroscopic analysis was carried out on a total of 139 complete skeletons of mangabeys, colobines and guenons. Species in multi-male groups were found to have higher fracture frequencies than those in uni-male groups. These higher frequencies may be related to intra-specific male-male aggression; however, similarities in fracture patterning between males and females in multi-male groups suggest that other factors may be involved. Although fracture etiology may not be identified with certainty, this study suggests that predation may indirectly be a cause of traumatic injuries in those species of cercopithecid monkeys displaying multi-male social organizations. The data presented also highlight the utility of museum collections as an additional resource in analyses of primate behavior, demonstrating that behavioral information does not die when the animal does.

An isolated cryptococcal urinary tract infection in a cat.

A male domestic shorthaired cat was presented for evaluation of stranguria and pollakiuria. A cryptococcal urinary tract infection (UTI) was diagnosed cytologically and via fungal culture. No evidence of systemic involvement was found. Chronic renal failure was a concurrent disease in this cat. Treatment consisted of oral fluconazole. Clinical signs resolved after 2 weeks of therapy, and fluconazole was discontinued after 6 months when negative urine culture results indicated resolution of the infection. This case demonstrates that correct identification of cryptococcal UTI allows for administration of therapy that can be associated with resolution of clinical signs.

GW domains of the Listeria monocytogenes invasion protein InlB are required for potentiation of Met activation.

The Listeria monocytogenes protein InlB promotes intracellular invasion by activating the receptor tyrosine kinase Met. Earlier studies have indicated that the LRR fragment of InlB is sufficient for Met activation, but we show that this is not the case unless the LRR fragment is artificially dimerized through a disulphide bond. In contrast, activation of Met proceeds through monomers of intact InlB and, at physiologically relevant concentrations, requires coordinated action in cis of both InlB N-terminal LRR region and C-terminal GW domains. The GW domains are shown to be crucial for potentiating Met activation and inducing intracellular invasion, with these effects depending on association between GW domains and glycosaminoglycans. Glycosaminoglycans do not alter the monomeric state of InlB, and are likely to enhance Met activation through a receptor-mediated mode, as opposed to the ligand-mediated mode observed for the LRR fragment. Surprisingly, we find that gC1q-R, a host protein implicated in InlB-mediated invasion, specifically antagonizes rather than enhances InlB signalling, and that interaction between InlB and gC1q-R is unnecessary for bacterial invasion. Lastly, we demonstrate that HGF, the endogenous ligand of Met, substitutes for InlB in promoting intracellular invasion, suggesting that no special properties are required of InlB in invasion besides its hormone-like mimicry of HGF.

Characterization of the calcium-binding sites of Listeria monocytogenes InlB.

The Listeria monocytogenes protein InlB promotes invasion of mammalian cells through activation of the receptor tyrosine kinase Met. The InlB N-cap, a approximately 40 residue part of the domain that binds Met, was previously observed to bind two calcium ions in a novel and unusually exposed manner. Because subsequent work raised questions about the existence of these calcium-binding sites, we assayed calcium binding in solution to the InlB N-cap. We show that calcium ions are bound with dissociation constants in the low micromolar range at the two identified sites, and that the sites interact with one another. We demonstrate that the calcium ions are not required for structure, and also find that they have no appreciable effect on Met activation or intracellular invasion. Therefore, our results indicate that the sites are fortuitous in InlB, but also suggest that the simple architecture of the sites may be adaptable for protein engineering purposes.

Crystal structure of LIR-2 (ILT4) at 1.8 A: differences from LIR-1 (ILT2) in regions implicated in the binding of the Human Cytomegalovirus class I MHC homolog UL18.

BACKGROUND: Leukocyte Immunoglobulin-like Receptor-1 (LIR-1) and LIR-2 (also known as ILT2 and ILT4 respectively) are highly related cell surface receptors that bind a broad range of class I MHC molecules with low (microM) affinities. Expressed on monocytic cells and macrophages, both molecules transmit inhibitory signals after binding ligands. In addition to binding host class I MHC, the LIR-1 molecule, which is also expressed on lymphoid tissues, binds with a high (nM) affinity to UL18, a class I MHC homolog encoded by Human Cytomegalovirus (HCMV). In comparison, LIR-2 binds UL18 only weakly (microM KD). To understand how HCMV preferentially targets the more broadly expressed LIR-1 molecule, we determined the crystal structure of a ligand-binding fragment of LIR-2, and compared this to the existing high-resolution crystal structure of LIR-1. RESULTS: Recombinant LIR-2 (domains 1 and 2) was produced in E. coli and crystallized using streak seeding to optimize the crystal morphology. A data set complete to 1.8 A was collected at 100 K from a single crystal in the P4(1)2(1)2 spacegroup. The structure was solved by molecular replacement, using a search model based on the LIR-1 structure. CONCLUSIONS: The overall structure of LIR-2 D1D2 resembles both LIR-1, and Killer Inhibitory Receptors, in that the A strand in each domain forms hydrogen bonds to both beta sheets, and there is a sharp angle between the two immunoglobulin-like domains. However, differences from LIR-1 are observed in each domain, with two key changes apparent in the ligand-binding domain, D1. The region corresponding to the residue 44-57 helix of LIR-1 adopts a topology distinct from that of both LIR-1 and the KIR structures, involving a shortened 310 helix. Secondly, the predicted UL18 binding region of LIR-1 is altered substantially in LIR-2: the 76-84 loop mainchain is displaced 11 A with respect to LIR-1, and Tyrosine 38 adopts an alternative rotamer conformation. In summary, the structure of LIR-2 has revealed significant differences to LIR-1, including ones that may help to explain the >1000-fold lower affinity of LIR-2 for UL18.