Computational fluid dynamic simulations of maternal circulation : wall shear stress in the human placenta and its biological implications

Introduction In the human placenta the maternal blood circulates in the intervillous space (IVS). The syncytiotrophoblast (STB) is in direct contact with maternal blood. The wall shear stress (WSS) exerted by the maternal blood flow on the STB has not been evaluated. Our objective was to determine the physiological WSS exerted on the surface of the STB during the third trimester of pregnancy. Material and Methods To gain insight into the shear stress levels that the STB is expected to experience in vivo, we have formulated three different computational models of varying levels of complexity that reflect different physical representations of the IVS. Computations of the flow fields in all models were performed using the CFD module of the finite element code COMSOL Multi-physics 4.4. The mean velocity of maternal blood in the IVS during the third trimester was measured in vivo with dynamic MRI (0.94 +/- 0.14 mm.s(-1)). To investigate if the in silico results are consistent with physiological observations, we studied the cytoadhesion of human parasitized (Plasmodium falciparum) erythrocytes to primary human STB cultures, in flow conditions with different WSS values. Results The WSS applied to the STB is highly heterogeneous in the IVS. The estimated average values are relatively low (0.5 +/- 0.2 to 2.3 +/- 1.1 dyn.cm(-2)). The increase of WSS from 0.15 to 5 dyn.cm(-2) was associated with a significant decrease of infected erythrocyte cytoadhesion. No cytoadhesion of infected erythrocytes was observed above 5 dyn.cm(-2) applied for one hour. Conclusion Our study provides for the first time a WSS estimation in the maternal placental circulation. In spite of high maternal blood flow rates, the average WSS applied at the surface of the chorionic villi is low (<5 dyn.cm(-2)). These results provide the basis for future physiologicallyrelevant in vitro studies of the biological effects of WSS on the STB

Genome-wide, high-content siRNA screening identifies the Alzheimer's genetic risk factor FERMT2 as a major modulator of APP metabolism

Genome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer’s disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the “post-GWAS” era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective. We therefore developed a genome-wide, high-content siRNA screening approach and used it to assess the functional impact of gene under-expression on APP metabolism. We found that 832 genes modulated APP metabolism. Eight of these genes were located within AD susceptibility loci. Only FERMT2 (a β3-integrin co-activator) was also significantly associated with a variation in cerebrospinal fluid Aβ peptide levels in 2886 AD cases. Lastly, we showed that the under-expression of FERMT2 increases Aβ peptide production by raising levels of mature APP at the cell surface and facilitating its recycling. Taken as a whole, our data suggest that FERMT2 modulates the AD risk by regulating APP metabolism and Aβ peptide production

Lucy's Flat Feet: The Relationship between the Ankle and Rearfoot Arching in Early Hominins

BACKGROUND. In the Plio-Pleistocene, the hominin foot evolved from a grasping appendage to a stiff, propulsive lever. Central to this transition was the development of the longitudinal arch, a structure that helps store elastic energy and stiffen the foot during bipedal locomotion. Direct evidence for arch evolution, however, has been somewhat elusive given the failure of soft-tissue to fossilize. Paleoanthropologists have relied on footprints and bony correlates of arch development, though little consensus has emerged as to when the arch evolved. METHODOLOGY/PRINCIPAL FINDINGS. Here, we present evidence from radiographs of modern humans (n=261) that the set of the distal tibia in the sagittal plane, henceforth referred to as the tibial arch angle, is related to rearfoot arching. Non-human primates have a posteriorly directed tibial arch angle, while most humans have an anteriorly directed tibial arch angle. Those humans with a posteriorly directed tibial arch angle (8%) have significantly lower talocalcaneal and talar declination angles, both measures of an asymptomatic flatfoot. Application of these results to the hominin fossil record reveals that a well developed rearfoot arch had evolved in Australopithecus afarensis. However, as in humans today, Australopithecus populations exhibited individual variation in foot morphology and arch development, and "Lucy" (A.L. 288-1), a 3.18 Myr-old female Australopithecus, likely possessed asymptomatic flat feet. Additional distal tibiae from the Plio-Pleistocene show variation in tibial arch angles, including two early Homo tibiae that also have slightly posteriorly directed tibial arch angles. CONCLUSIONS/SIGNIFICANCE. This study finds that the rearfoot arch was present in the genus Australopithecus. However, the female Australopithecus afarensis "Lucy" has an ankle morphology consistent with non-pathological flat-footedness. This study suggests that, as in humans today, there was variation in arch development in Plio-Pleistocene hominins.Leakey Foundatio

The evolution of the upright posture and gait—a review and a new synthesis

During the last century, approximately 30 hypotheses have been constructed to explain the evolution of the human upright posture and locomotion. The most important and recent ones are discussed here. Meanwhile, it has been established that all main hypotheses published until the last decade of the past century are outdated, at least with respect to some of their main ideas: Firstly, they were focused on only one cause for the evolution of bipedality, whereas the evolutionary process was much more complex. Secondly, they were all placed into a savannah scenario. During the 1990s, the fossil record allowed the reconstruction of emerging bipedalism more precisely in a forested habitat (e.g., as reported by Clarke and Tobias (Science 269:521–524, 1995) and WoldeGabriel et al. (Nature 412:175–178, 2001)). Moreover, the fossil remains revealed increasing evidence that this part of human evolution took place in a more humid environment than previously assumed. The Amphibian Generalist Theory, presented first in the year 2000, suggests that bipedalism began in a wooded habitat. The forests were not far from a shore, where our early ancestor, along with its arboreal habits, walked and waded in shallow water finding rich food with little investment. In contrast to all other theories, wading behaviour not only triggers an upright posture, but also forces the individual to maintain this position and to walk bipedally. So far, this is the only scenario suitable to overcome the considerable anatomical and functional threshold from quadrupedalism to bipedalism. This is consistent with paleoanthropological findings and with functional anatomy as well as with energetic calculations, and not least, with evolutionary psychology. The new synthesis presented here is able to harmonise many of the hitherto competing theories

Thermomechanical analysis applied to the laser beam welding simulation of aeronautical structures

The present work is being done in the framework of a national program about the lightening of aeronautical structures and describes a three-dimensional finite element simulation of the laser beam welding process. The targeted aeronautical structures are stiffened panels in aluminum alloys, which tend to replace riveted assemblies. Semi-coupled thermomechanical finite element analyses have been carried out to evaluate the magnitude and distribution of welding-induced residual stresses in order to take them into account for fatigue sizing. The finite element code MSC.Marc is used for the different calculations. Specific welding features have been added to the code through the implementation of a moving heat source or an elastoviscoplastic law. Experimental tests have been carried out in order to provide mechanical and thermal databases to the model. Monitored experimental welding have been made for comparisons with the simulation. In particular, results of thermocouple measurements have permitted to improve the thermal model

A simple Eulerian thermomechanical modeling of friction stir welding

International audienceA simple three-dimensional thermomechanical model for friction stir welding (FSW) is presented. It is developed from the model proposed by Heurtier et al. (2006) based on a combination of fluid mechanics numerical and analytical velocity fields. Those velocity fields are introduced in a steady state thermal calculation to compute the temperature field during welding. They allow partial sliding between the shoulder and the workpiece, the amount of which is provided as an additional result of the model. The thermal calculation accounts for conduction and convection effects by means of the particular derivative. The complete thermomechanical history of the material during the process can then be accessed by temperature and strain rate contours. The numerical results are compared with a set of experimental test cases carried out on an instrumented laboratory device. The choices for modeling assumptions, especially tribological aspects, are discussed according to agreements or deviations observed between experimental and numerical results. The amount of sliding appears to be significantly influenced by the welding conditions (welding and tool rotational velocities), and physical interpretations are proposed for its evolution

Comment je fais… L’examen échographique de l’œsophage au premier trimestre

International audienceComment je fais.. . L'examen e ´chographique de l'oesophage au premier trimestre How I do.. . fetal esophagus sonographic assessment in the first trimeste