Three-dimensional modeling of human placental terminal villi.

INTRODUCTION: Placental transport is the main factor affecting the health and development of the fetus. Due to the placenta's geometrical and mathematical complexity, the structure-function relations of placental terminal villi have not been successfully modeled. Hence, a novel modeling approach is proposed. METHODS: Computational models of four different specimens were generated from the three-dimensional reconstruction of confocal laser scanning microscopic image stacks. To evaluate the capabilities of the proposed methodology, stationary oxygen diffusion transport was calculated in the terminal villus volumes. RESULTS: The reconstructions automatically provided the spatial arrangement of the fetal capillaries inside the terminal villi. The surface and volume ratios between the fetal capillaries and the villus were also calculated, and the effects of model parameters on the placental diffusive capacity were assessed by parametric analysis. DISCUSSION: The potential of three-dimensional reconstructions combined with finite element analysis as a research tool for the human placenta was tested. The methodology herein could serve in the future as a simulation platform for complicated in vivo and in vitro scenarios.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.placenta.2016.05.00

Three-dimensional morphological analysis of placental terminal villi.

Transport of nutrients and waste between the maternal and fetal circulations during pregnancy takes place at the final branches of the placental villous trees. Therefore, and unsurprisingly, pregnancy complications have been related to the maldevelopment of terminal villi. However, a deep analysis of placental villous morphology has been limited by tissue processing and imaging techniques. In this proof-of-principle study, placental lobules were fixed by perfusion and small clumps of villi were stained, sectioned optically and reconstructed. Morphological and network analyses were suggested and demonstrated on samples of normal placentas. The results show that most parameters are almost constant within a placenta but that there exists an inter-individual variation. Network analysis suggests that the feto-placental capillary network has several paths within an individual villus, serving as an efficient transport system. Three-dimensional reconstruction from confocal laser scanning microscopy images is a potent technique able to quantify placental architecture and capture the significant irregularities in vessel diameter and membrane thickness. This approach has the potential to become a powerful tool to further our understanding of the differences in placental structure which may underlie pregnancy complications

Odorant transport in a hagfish

Odorant transport is of fundamental and applied importance. Using computational simulations, we studied odorant transport in an anatomically accurate model of the nasal passage of a hagfish (probably Eptatretus stoutii). We found that ambient water is sampled widely, with a significant ventral element. Additionally, there is a bilateral element to olfactory flow, which enters the single nostril in two narrow, laminar streams that are then split prior to the nasal chamber by the anterior edge of the central olfactory lamella. An appendage on this lamella directs a small portion (10–14%) of the overall nasal flow to the olfactory sensory channels. Much of the remaining flow is diverted away from the sensory channels by two peripheral channels. The anterior edge of the central olfactory lamella, together with a jet-impingement mechanism, disperses flow over the olfactory surfaces. Diffusion of odorant from bulk water to the olfactory surfaces is facilitated by the large surface area:volume ratio of the sensory channels, and by a resistance-based hydrodynamic mechanism that leads to long residence times (up to 4.5 s) in the sensory channels. With increasing volumetric flow rate, the rate of odorant transfer to the olfactory surfaces increases, but the efficiency of odorant uptake decreases, falling in the range 2–6%. Odorant flux decreases caudally across the olfactory surfaces, suggesting in vivo a preponderance of olfactory sensory neurons on the anterior part of each olfactory surface. We conclude that the hagfish has a subtle anatomy for locating and capturing odorant molecules

Laser Sounder Approach for Global Measurement of Tropospheric CO2 Mixing Ratio from Space

We report progress in assessing the feasibility of a new satellite-based laser-sounding instrument to measure CO2 and other trace gas abundances in the lower troposphere from space

Synthesis of a series of novel 3,9-disubstituted phenanthrenes as analogues of known <i>N</i>-methyl-D-aspartate receptor allosteric modulators

9-Substituted phenanthrene-3-carboxylic acids have been reported to have allosteric modulatory activity at the NMDA receptor. This receptor is activated by the excitatory neurotransmitter L-glutamate and has been implicated in a range of neurological disorders such as schizophrenia, epilepsy and chronic pain and neurodegenerative disorders such as Alzheimer’s disease. Herein, the convenient synthesis of a wide range of novel 3,9-disubstituted phenanthrene derivatives starting from a few common intermediates is described. These new phenanthrene derivatives will help to clarify the structural requirements for allosteric modulation of the NMDA receptor

Requirement of NF-κB activation to suppress p53-independent apoptosis induced by oncogenic ras

The ras proto-oncogene is frequently mutated in human tumors and functions to chronically stimulate signal transduction cascades resulting in the synthesis or activation of specific transcription factors, including Ets, c-Myc, c-Jun, and nuclear factor kappa B (NF-kappaB). These Ras-responsive transcription factors are required for transformation, but the mechanisms by which these proteins facilitate oncogenesis have not been fully established. Oncogenic Ras was shown to initiate a p53-independent apoptotic response that was suppressed through the activation of NF-kappaB. These results provide an explanation for the requirement of NF-kappaB for Ras-mediated oncogenesis and provide evidence that Ras-transformed cells are susceptible to apoptosis even if they do not express the p53 tumor-suppressor gene product

Synergizing expectation and execution for stroke communities of practice innovations

<p>Abstract</p> <p>Background</p> <p>Regional networks have been recognized as an interesting model to support interdisciplinary and inter-organizational interactions that lead to meaningful care improvements. Existing communities of practice within the a regional network, the Montreal Stroke Network (MSN) offers a compelling structure to better manage the exponential growth of knowledge and to support care providers to better manage the complex cases they must deal with in their practices. This research project proposes to examine internal and external factors that influence individual and organisational readiness to adopt national stroke best practices and to assess the impact of an e-collaborative platform in facilitating knowledge translation activities.</p> <p>Methods</p> <p>We will develop an e-collaborative platform that will include various social networking and collaborative tools. We propose to create online brainstorming sessions ('jams') around each best practice recommendation. Jam postings will be analysed to identify emergent themes. Syntheses of these analyses will be provided to members to help them identify priority areas for practice change. Discussions will be moderated by clinical leaders, whose role will be to accelerate crystallizing of ideas around 'how to' implement selected best practices. All clinicians (~200) involved in stroke care among the MSN will be asked to participate. Activities during face-to-face meetings and on the e-collaborative platform will be documented. Content analysis of all activities will be performed using an observation grid that will use as outcome indicators key elements of communities of practice and of the knowledge creation cycle developed by Nonaka. Semi-structured interviews will be conducted among users of the e-collaborative platform to collect information on variables of the knowledge-to-action framework. All participants will be asked to complete three questionnaires: the typology questionnaire, which classifies individuals into one of four mutually exclusive categories of information seeking; the e-health state of readiness, which covers ten domains of the readiness to change; and a community of practice evaluation survey.</p> <p>Summary</p> <p>This project is expected to enhance our understanding of collaborative work across disciplines and organisations in accelerating implementation of best practices along the continuum of care, and how e-technologies influence access, sharing, creation, and application of knowledge.</p