Plasma cell precursors: long-distance travelers looking for a home.

Little is known about the migration of plasma cell precursors to the lymph node medulla. In this issue of Immunity, Fooksman et al. (2010) propose that this migration is largely independent of chemotactic cues but follows a long linear walk of random orientation.

Multi-segment foot kinematics after total ankle replacement and ankle arthrodesis during relatively long-distance gait.

This study aimed to investigate the influence of ankle osteoarthritis (AOA) treatments, i.e., ankle arthrodesis (AA) and total ankle replacement (TAR), on the kinematics of multi-segment foot and ankle complex during relatively long-distance gait. Forty-five subjects in four groups (AOA, AA, TAR, and control) were equipped with a wearable system consisting of inertial sensors installed on the tibia, calcaneus, and medial metatarsals. The subjects walked 50-m twice while the system measured the kinematic parameters of their multi-segment foot: the range of motion of joints between tibia, calcaneus, and medial metatarsals in three anatomical planes, and the peaks of angular velocity of these segments in the sagittal plane. These parameters were then compared among the four groups. It was observed that the range of motion and peak of angular velocities generally improved after TAR and were similar to the control subjects. However, unlike AOA and TAR, AA imposed impairments in the range of motion in the coronal plane for both the tibia-calcaneus and tibia-metatarsals joints. In general, the kinematic parameters showed significant correlation with established clinical scales (FFI and AOFAS), which shows their convergent validity. Based on the kinematic parameters of multi-segment foot during 50-m gait, this study showed significant improvements in foot mobility after TAR, but several significant impairments remained after AA.

Influence of inter-electrode distance, contraction type, and muscle on the relationship between the sEMG power spectrum and contraction force.

INTRODUCTION: Spectral frequencies of the surface electromyogram (sEMG) increase with contraction force, but debate still exists on whether this increase is affected by various methodological and anatomical factors. This study aimed to investigate the influence of inter-electrode distance (IED) and contraction modality (step-wise vs. ramp) on the changes in spectral frequencies with increasing contraction strength for the vastus lateralis (VL) and vastus medialis (VM) muscles. METHODS: Twenty healthy male volunteers were assessed for isometric sEMG activity of the VM and VL, with the knee at 90° flexion. Subjects performed isometric ramp contractions in knee extension (6-s duration) with the force gradually increasing from 0 to 80 % MVC. Also, subjects performed 4-s step-wise isometric contractions at 10, 20, 30, 40, 50, 60, 70, and 80 % MVC. Interference sEMG signals were recorded simultaneously at different IEDs: 10, 20, 30, and 50 mm. The mean (F mean) and median (F median) frequencies and root mean square (RMS) of sEMG signals were calculated. RESULTS: For all IEDs, contraction modalities, and muscles tested, spectral frequencies increased significantly with increasing level of force up to 50-60 % MVC force. Spectral indexes increased systematically as IED was decreased. The sensitivity of spectral frequencies to changes in contraction force was independent of IED. The behaviour of spectral indexes with increasing contraction force was similar for step-wise and ramp contractions. CONCLUSIONS: In the VL and VM muscles, it is highly unlikely that a particular inter-electrode distance or contraction modality could have prevented the observation of the full extent of the increase in spectral frequencies with increasing force level.

Phenotypic divergence but not genetic distance predicts assortative mating among species of a cichlid fish radiation.

The hypothesis of ecological divergence giving rise to premating isolation in the face of gene flow is controversial. However, this may be an important mechanism to explain the rapid multiplication of species during adaptive radiation following the colonization of a new environment when geographical barriers to gene flow are largely absent but underutilized niche space is abundant. Using cichlid fish, we tested the prediction of ecological speciation that the strength of premating isolation among species is predicted by phenotypic rather than genetic distance. We conducted mate choice experiments between three closely related, sympatric species of a recent radiation in Lake Mweru (Zambia/DRC) that differ in habitat use and phenotype, and a distantly related population from Lake Bangweulu that resembles one of the species in Lake Mweru. We found significant assortative mating among all closely related, sympatric species that differed phenotypically, but none between the distantly related allopatric populations of more similar phenotype. Phenotypic distance between species was a good predictor of the strength of premating isolation, suggesting that assortative mating can evolve rapidly in association with ecological divergence during adaptive radiation. Our data also reveals that distantly related allopatric populations that have not diverged phenotypically, may hybridize when coming into secondary contact, e.g. upon river capture because of diversion of drainage systems.

Ostéogénèse atypique après séquestrectomies multiples pour fracture ouverte infectée du fémur: un cas [Atypical osteogenesis following multiple sequestrectomies for infected open fracture of the femur: a case]

The authors present the case of an open fracture of femur Cauchoix type II with an infection due to Escherichia coli, Clostridium perfringens, Enterococcus and Aspergillus fumigatus. After several sequestrectomies and five hyperbaric sessions, apyrexia was attained at the end of the third month, the femur having been stabilised with an external fixator. The 15 cm gap due to loss of bone substance, filled at each dressing with an antiseptic iodine based ointment, closed itself finishing as continuous bone five months after the accident, the granulation tissue having been recovered by thin skin grafts. A repeated fracture occurring forty-eight hours after the removal of the Hoffmann frame was treated by fitting an Ilizarov fixator arriving at consolidation in seven months. The authors examine different possibilities of accelerating osteogenesis and highlight the potential role of iodine ointment as inductive to osteogenesis stemming from a periosteal layer seemingly held in place.

Evaluation of a mixed approach combining stationary and wearable systems to monitor gait over long distance.

Thanks to decades of research, gait analysis has become an efficient tool. However, mainly due to the price of the motion capture systems, standard gait laboratories have the capability to measure only a few consecutive steps of ground walking. Recently, wearable systems were proposed to measure human motion without volume limitation. Although accurate, these systems are incompatible with most of existing calibration procedures and several years of research will be necessary for their validation. A new approach consisting of using a stationary system with a small capture volume for the calibration procedure and then to measure gait using a wearable system could be very advantageous. It could benefit from the knowledge related to stationary systems, allow long distance monitoring and provide new descriptive parameters. The aim of this study was to demonstrate the potential of this approach. Thus, a combined system was proposed to measure the 3D lower body joints angles and segmental angular velocities. It was then assessed in terms of reliability towards the calibration procedure, repeatability and concurrent validity. The dispersion of the joint angles across calibrations was comparable to those of stationary systems and good reliability was obtained for the angular velocities. The repeatability results confirmed that mean cycle kinematics of long distance walks could be used for subjects' comparison and pointed out an interest for the variability between cycles. Finally, kinematics differences were observed between participants with different ankle conditions. In conclusion, this study demonstrated the potential of a mixed approach for human movement analysis.

Mutations in FKBP10 cause recessive osteogenesis imperfecta and Bruck syndrome.

Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue characterized by bone fragility and alteration in synthesis and posttranslational modification of type I collagen. Autosomal dominant OI is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen. Bruck syndrome is a recessive disorder featuring congenital contractures in addition to bone fragility; Bruck syndrome type 2 is caused by mutations in PLOD2 encoding collagen lysyl hydroxylase, whereas Bruck syndrome type 1 has been mapped to chromosome 17, with evidence suggesting region 17p12, but the gene has remained elusive so far. Recently, the molecular spectrum of OI has been expanded with the description of the basis of a unique posttranslational modification of type I procollagen, that is, 3-prolyl-hydroxylation. Three proteins, cartilage-associated protein (CRTAP), prolyl-3-hydroxylase-1 (P3H1, encoded by the LEPRE1 gene), and the prolyl cis-trans isomerase cyclophilin-B (PPIB), form a complex that is required for fibrillar collagen 3-prolyl-hydroxylation, and mutations in each gene have been shown to cause recessive forms of OI. Since then, an additional putative collagen chaperone complex, composed of FKBP10 (also known as FKBP65) and SERPINH1 (also known as HSP47), also has been shown to be mutated in recessive OI. Here we describe five families with OI-like bone fragility in association with congenital contractures who all had FKBP10 mutations. Therefore, we conclude that FKBP10 mutations are a cause of recessive osteogenesis imperfecta and Bruck syndrome, possibly Bruck syndrome Type 1 since the location on chromosome 17 has not been definitely localized.

Phenotypic and molecular characterization of Bruck syndrome (Osteogenesis imperfecta with contractures of the large joints) caused by a recessive mutation in PLOD2

Le Syndrome de Bruck (Bruck Syndrome; BS) est une maladie autosomique récessive assemblant la combinaison inhabituelle de fragilité osseuse semblable à celle de l'Ostéogenèse Imparfaite (0I) avec des contractures congénitales tendineuses et cutanées des grandes articulations («ptérygia»). Les cas décrits jusqu'à ce jour mettent en évidence une grande hétérogénéité du tableau clinique, liée en partie au manque d'un diagnostic biochimique ou moléculaire. Nous savons que dans le BS les gènes codant pour le collagène 1 ne sont pas mutés, mais savons néanmoins, grâce à l'étude du collagène extrait de biopsies osseuses, qu'il y a un déficit d'hydroxylation des résidus de lysine dans les télopeptides du collagène 1 qui servent à la formation des liens intermoléculaires (crosslinks) et donc à la stabilisation des fibres de collagène. Un locus génétique du BS à été mappé sur 17q12, mais le gène responsable sur ce locus reste inconnu; plus récemment, deux mutations dans le gène de la lysyl hydroxylase 2 (PLOD2, position chromosomique 3q23-q24) ont été identifiées, démontrant l'hétérogénéité génétique du ES. La proportion de ES liée à 17p22 (BS type 1) et celle liée à une mutation dans PLOD2 (BS type 2) est encore incertaine et nous manquons de données sur la corrélation phenotype-génotype. Nous avons étudié le cas d'un garçon avec des contractures et des ptérygia dès la naissance, combinées à une ostéopénie sévère de type OI menant à des fractures multiples. Ses urines contenaient une quantité élevée d'hydroxyproline, indiquant un remaniement important du tissu osseux, mais peu de produits de dégradation des crosslinks du collagène, indiquant donc une réduction de la proportion de crosslinks dans le collagène in vivo. Nous avons pu démontrer chez lui la présence d'une nouvelle mutation homozygote dans le gène PLOD2 menant à une substitution Arg598His; les deux parents du sujet étaient hétérozygotes pour la mutation et celle-ci était absente dans notre population témoin. La mutation est adjacente aux deux mutations rapportées précédemment (Gly601Val et Thr608Ile), ce qui suggère la présence d'un ''hotspot'' mutationnel mais aussi d'une région de grande importance fonctionnelle sur PLOD2 : cette observation est importante pour la création d'inhibiteurs de PLOD2, recherchés en ce moment pour le traitement de la fibrose. La combinaison de ptérygia et de fragilité osseuse, comme illustrée par notre patient est apparemment contradictoire et donc difficilement explicable mais indique que l'hydroxylation des résidus lysyl des télopeptides est importante non seulement pour la stabilité osseuse mais aussi dans la morphogénèse et la formation des articulations dans la période prénatale. Finalement, la mesure des produits de dégradation du collagène dans l'urine et l'analyse de mutation de PLOD2 permet le diagnostic du syndrome de Bruck et permet de le différencier de l'Osteogénèse Imparfaite. -- Bruck syndrome (BS) is a recessively-inherited phenotypic disorder featuring the unusual combination of skeletal changes resembling osteogenesis imperfecta (0I) with congenital contractures of the large joints. Clinical heterogeneity is apparent in cases reported thus far. While the genes coding for collagen 1 chains are unaffected in BS, there is biochemical evidence for a defect in the hydroxylation of lysine residues in collagen 1 telopeptides. One BS locus has been mapped at 17p12, but more recently, two mutations in the lysyl hydroxylase 2 gene (PLOD2, 3q23-q24) have been identified in BS, showing genetic heterogeneity. The proportion of BS cases linked to 17p22 (BS type 1) or caused by mutations in PLOD2 (BS type 2) is still uncertain, and phenotypic correlations are lacking. We report on a boy who had congenital contractures with pterygia at birth and severe 0I-like osteopenia and multiple frac-tures. His urine contained high amounts of hydroxyproline but low amounts of collagen crosslinks degradation products; and he was shown to be homozygous for a novel mutation leading to an Arg598His substitution in PLOD2. The mutation is adjacent to the two mutations previously reported (Gly601Val and Thr608Ile), suggesting a functionally important hotspot in PLOD2. The combination of pterygia with bone fragility, as illustrated by this case, is difficult to explain; it suggests that telopeptide lysyl hydroxylation must be involved in prenatal joint formation and morphogenesis. Collagen degradation products in urine and mutation analysis ofPLOD2 maybe used to diagnose BS and differentiate it from M.

Measuring and Explaining the Increase of Travel Distance : A Multilevel Analysis Using Repeated Cross Sectional Travel Surveys

We want to shed some light on the development of person mobility by analysing the repeated cross-sectional data of the four National Travel Surveys (NTS) that were conducted in Germany since the mid seventies. The above mentioned driving forces operate on different levels of the system that generates the spatial behaviour we observe: Travel demand is derived from the needs and desires of individuals to participate in spatially separated activities. Individuals organise their lives in an interactive process within the context they live in, using given infrastructure. Essential determinants of their demand are the individual's socio-demographic characteristics, but also the opportunities and constraints defined by the household and the environment are relevant for the behaviour which ultimately can be realised. In order to fully capture the context which determines individual behaviour, the (nested) hierarchy of persons within households within spatial settings has to be considered. The data we will use for our analysis contains information on these three levels. With the analysis of this micro-data we attempt to improve our understanding of the afore subsumed macro developments. In addition we will investigate the prediction power of a few classic sociodemographic variables for the daily travel distance of individuals in the four NTS data sets, with a focus on the evolution of this predictive power. The additional task to correctly measure distances travelled by means of the NTS is threatened by the fact that although these surveys measure the same variables, different sampling designs and data collection procedures were used. So the aim of the analysis is also to detect variables whose control corrects for the known measurement error, as a prerequisite to apply appropriate models in order to better understand the development of individual travel behaviour in a multilevel context. This task is complicated by the fact that variables that inform on survey procedures and outcomes are only provided with the data set for 2002 (see Infas and DIW Berlin, 2003).

Truncated robust distance for clinical laboratory safety data monitoring and assessment.

Laboratory safety data are routinely collected in clinical studies for safety monitoring and assessment. We have developed a truncated robust multivariate outlier detection method for identifying subjects with clinically relevant abnormal laboratory measurements. The proposed method can be applied to historical clinical data to establish a multivariate decision boundary that can then be used for future clinical trial laboratory safety data monitoring and assessment. Simulations demonstrate that the proposed method has the ability to detect relevant outliers while automatically excluding irrelevant outliers. Two examples from actual clinical studies are used to illustrate the use of this method for identifying clinically relevant outliers.

Sex differences in the computation of traveling distance

Path integration is known to provide information to keep track of spatial location. Surprisingly, few investigations concerning sex differences in computation of the traveling distance have been done. This work was aimed at analyzing the reproduction of both passive and active linear displacements in women and men. To this end, the displacement of blindfolded subjects was done in a wheelchair, then on foot, three times in each condition for a fixed distance. Copies of passive and active traveling distance, distance estimations and pointing responses towards the starting point were analyzed. In passive condition and comparatively to men, women error was larger. Whereas traveling distance was generally underestimated in women, it was overestimated in men. In active condition, no sex differences were observed. When blindfolded subjects have to estimate the traveling distance, the female error was larger than the male one. But, when subjects were asked to indicate the visual cue corresponding to the traveling distance, the male error was larger than the female one. Finally, pointing to the starting point (0°) after a whole-body rotation showed a larger deviation from 0° in men than in women. These results suggest that sex of the subjects influence brain computation of path integration information.