Wall shear stress and arterial performance: two approaches based on engineering

This is the Abstract of the Article. Copyright @ 2009 Oxford University.This crucially important subject generates a very wide literature and the recent authoritative ‘in vivo’ review of Reneman et al [1] (& [2]), with Vennemann et al [3], are taken as seminal. In this paper we use approaches based on conventional engineering to address two key issues raised in [1]. The first is that of basic theory. To what extent can underlying fluid flow theory complement the in vivo understanding of wall shear stress (WSS)? In [1], which is sub-titled Discrepancies with Theory’, Poiseuille’s Law is used, extended to Murray’s Law in [2]. But they do ’not hold in vivo’ [2] because ‘we are dealing with non-Newtonian fluid, distensible vessels, unsteady flows, and too short entrance lengths’ [1].This comment coincides with the four factors Xu and Collins identified in their early Review of numerical analysis for bifurcations [4]. Subsequently they addressed these factors, with an engineering-based rationale of comparing predictions of Computational Fluid Dynamics (CFD) with Womersley theory, in vitro and in vivo data. This rationale has yet to be widely adopted, possibly due to computing complexities and the wide boundary condition data needed. This is despite uncertainties in current in vivo WSS [2]. Secondly, [1] and [2] focus on endothelial function. WSS is an ‘important determinant of arterial diameter’ and ‘mean (M)WSS is regulated locally’. One pointer is the possible importance of the glycocalyx, so that ‘endothelial cells are not seeing WSS’ and which ‘may be involved in the regulation of the total blood flow’ [3]. A typical glycocalyx is shown in [3]. Such a model should focus on adaptation of arterial diameter by ‘nitric oxide and prostaglandins’ [1]. So, using an engineering approach, can we construct a model for local regulation of MWSS? Again, remarks from [1]-[3] resonate with the conclusions of a review of nanoscale physiological flows [5] undertaken as part of an early Nanotechnology Initiative of the UK’s EPSRC. In [5] is illustrated the fractal nature of the intestinal villi-glycocalyx geometry, together with an engineering-style control loop for nitric oxide release and arterial diameter-flow rate control. Within our discussion we report two studies to obtain CFD predictive data very close to the endothelial surface. In both cases we compared two independent codes, respectively two CFD codes, and CFD and Lattice Boltzmann solvers. We also give an updated version of the endothelium control loop

The thermodynamics of metabolism, cardiovascular performance and exercise, in health and diabetes: The objective of clinical markers

Extensive experience in UK National Health Service metabolic syndrome/type 2 diabetes clinics highlights the need for convenient clinical marker(s) which can be readily used to indicate the success or otherwise of alternative therapies. In this paper we study the metabolic context of the healthy and diseased states, which points to the haemodynamics being a possible key in identifying candidate markers. Human metabolism relates to two elemental thermodynamic systems, the individual cell and the human body in its entirety. The fundamental laws of thermodynamics apply to humans, animals, and their individual cells for both healthy and diseased conditions. as they are to classic heat engines. In compliance with the second law enhanced levels of heat are generated under exercise, heat itself being another factor modulating the cardiovascular response to physical exercise. Nutrients and oxygen uptake occurs via the digestive system and lungs, respectively, leading to ATP production by the established metabolic pathways: this is controlled by insulin. These are then delivered to the cells via the haemodynamic system to satisfy local metabolic need. The supply and demand of oxygen are finely regulated, in part, via oxygen-dependent release of ATP from the circulating erythrocytes. Energy supply and demand are regulated to sustain muscle activity resulting in the body’s output of measurable thermodynamic work—i.e. exercise. Recently a dynamic pathway model allowing quantification of ATP release from the erythrocytes and its contribution to oxygen supply regulation has been published. However, metabolic uptake is well known to be greatly affected by disease such as the highly prevalent diabetes type 2 with insulin resistance and beta cell dysfunction having mechanistic roles. In 2010, over 25% of residents above 65 in the USA had diabetes 2. The complexity of the metabolic pathways means that monitoring of patient-specific treatment would be beneficial from a diabetic marker which may be haemodynamic-related and traceable via the local fluid dynamics

Morphological and Behavioural Features of Bewo Cells Grown on Matrigel Offers a Model for Human Cytotrophoblast Cells During Early Implantation

In order to observe the morphological changes that occur in cell-cell and cell-matrix interactions among trophoblast cells and other neighbouring cells during human implantation, BeWo cells were cultured in a 3-dimensional artificial extracellular matrix (Matrigel) using a double-chamber system. These cultures were then processed for light and electron microscopical examination. Results obtained show that the morphology and behavioural pattern of BeWo cells grown on Matrigel is similar to that reported for in vitro normal human cytotrophoblast cells on extracellular matrix (ECM). These results suggest that culture of BeWo cells on extracellular matrices may be useful for the study of some of the early embryonic events leading to human implantation, especially during the period when trophoblastic cells interact with and erode the uterine epithelium and ECM. Keywords: BeWo cells, Trophoblast, Morphology, Matrigel, implantation Journal of Science and Technology Vol. 28 (1) 2008 pp. 4-1

Transthyretin interacts with actin regulators in a Drosophila model of familial amyloid polyneuropathy

Familial amyloid polyneuropathy (FAP) is a neurodegenerative disorder whose major hallmark is the deposition of mutated transthyretin (TTR) in the form of amyloid fibrils in the peripheral nervous system (PNS). The exposure of PNS axons to extracellular TTR deposits leads to an axonopathy that culminates in neuronal death. However, the molecular mechanisms underlying TTR-induced neurodegeneration are still unclear, despite the extensive studies in vertebrate models. In this work we used a Drosophila FAP model, based on the expression of the amyloidogenic TTR (V30M) in the fly retina, to uncover genetic interactions with cytoskeleton regulators. We show that TTR interacts with actin regulators and induces cytoskeleton alterations, leading to axonal defects. Moreover, our study pinpoints an interaction between TTRV30M and members of Rho GTPase signaling pathways, the major actin regulators. Based on these findings we propose that actin cytoskeleton alterations may mediate the axonopathy observed in FAP patients, and highlight a molecular pathway, mediated by Rho GTPases, underlying TTR-induced neurodegeneration. We expect this work to prompt novel studies and approaches towards FAP therapy.This work was supported by: FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-028336 (PTDC/MED-NEU/28336/2017), to MAL; and Norte-01-0145-FEDER-000008—Porto Neurosciences and Neurologic Disease Research Initiative at I3S, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through FEDER, to CSL and MAL. MIOS is a FCT fellow (SFRH/ BD/118728/2016). CSL is funded by DL 57/2016/CP1355/CT0022. MAL is an FCT Investigator. Flies expressing wild-type and mutant alleles of TTR were kindly provided by Malgorzata Pokrzywa and Per Hammarström. The DCAD2, PDF and Rho1 monoclonal antibodies were obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. We would like to thank the SEM facility at CEMUP (University of Porto) for technical help and Mónica M Sousa and Fernando Casares for comments on the manuscript

Morphological Variations of the “Baby\'s Supply Line”

To contribute to the sparse information on dimensional variations of umbilical cords in Ghana, 124 placentae with attached umbilical cords were studied. The placentae were obtained from the University of Science and Technology Hospital between 2000 and 2002. Average cord length was 47.04cm (SD 12.8cm) with the shortest cord being 5.5cm and the longest 75.50cm. By empirical definition, 21.56% of the cords were Short whereas, 78.44% were long. Most of the umbilical cords (63%) had empirically eccentric attachments to their placentae; 20.48% had central and 16.52% had marginal attachments respectively. Occurrence of furcate insertion of umbilical cord vessels into the placenta was 28% and non-furcate insertion was 72%. These quantitative data provide baseline values for further investigation. Keywords: umbilical cords, morphology, length, attachments, looping, insertion Journal of Science and Technology Vol. 28 (2) 2008: pp. 1-

Microencapsulation As A Potential Control Technique Against Sabellid Worms In Abalone Culture

We have developed a novel application for lipid-walled microcapsules (LWMs) in the potential control of sabellid infestations in abalone aquaculture. The use of LWMs takes advantage of the filter-feeding nature of the worms, versus the herbivory of the host abalone. Initial observations indicated that the pest was capable of feeding on particles ranging from 3-30 mu m in size. Lipid-walled microcapsules were prepared using different combinations of lipids (tristearin, tripalmitin, and fish oil) to encapsulate water-based solutions. Feeding experiments using worm-infested shells indicated that in a relatively short time (30-60 min) most of the worms (80-95%) fed on the LWMs and that large numbers of LWMs were ingested. Fecal pellets containing LWMs were observed in the rectums of worms within 15-30 min. Feeding efficiency was examined using different concentrations of LWMs. The sabellid worm was an efficient feeder. At low particle densities (2.6 x 10(4) particles/mL), 66.7% of the worms had eaten modest levels of LWMs. An asymptote in particle density in relation to feeding occurred at 2.6 x 10(5) particles/mL, with 83% of the worms feeding on large numbers of particles. In separate observations, LWMs composed of tripalmitin and fish oil were observed in various stages of digestion in the stomach, rectum, and fecal pellets of the worms. Microcapsules were also observed in the digestive tract of mud worms, Polydora spp. that were also inhabiting abalone shell. The utility of LWMs for delivery of toxins to the sabellid pest holds much promise in ridding the industry of this nuisance species

A bifunctional kinase-phosphatase in bacterial chemotaxis.

addresses: Oxford Centre for Integrative Systems Biology and Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.notes: PMCID: PMC2587623types: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2008, The National Academy of SciencesPhosphorylation-based signaling pathways employ dephosphorylation mechanisms for signal termination. Histidine to aspartate phosphosignaling in the two-component system that controls bacterial chemotaxis has been studied extensively. Rhodobacter sphaeroides has a complex chemosensory pathway with multiple homologues of the Escherichia coli chemosensory proteins, although it lacks homologues of known signal-terminating CheY-P phosphatases, such as CheZ, CheC, FliY or CheX. Here, we demonstrate that an unusual CheA homologue, CheA(3), is not only a phosphodonor for the principal CheY protein, CheY(6), but is also is a specific phosphatase for CheY(6)-P. This phosphatase activity accelerates CheY(6)-P dephosphorylation to a rate that is comparable with the measured stimulus response time of approximately 1 s. CheA(3) possesses only two of the five domains found in classical CheAs, the Hpt (P1) and regulatory (P5) domains, which are joined by a 794-amino acid sequence that is required for phosphatase activity. The P1 domain of CheA(3) is phosphorylated by CheA(4), and it subsequently acts as a phosphodonor for the response regulators. A CheA(3) mutant protein without the 794-amino acid region lacked phosphatase activity, retained phosphotransfer function, but did not support chemotaxis, suggesting that the phosphatase activity may be required for chemotaxis. Using a nested deletion approach, we showed that a 200-amino acid segment of CheA(3) is required for phosphatase activity. The phosphatase activity of previously identified nonhybrid histidine protein kinases depends on the dimerization and histidine phosphorylation (DHp) domains. However, CheA(3) lacks a DHp domain, suggesting that its phosphatase mechanism is different from that of other histidine protein kinases

Formulation Of Artisanal Drink Based On Amaranthus Hypochondriacus L. Seeds

In this work, we sought to obtain a drink based on Amaranthus hypochondriacus L. seeds, highlighting the bromatological/nutritional and organoleptic properties (taste, aroma and appearance). Thus, develop a drink that combines the benefits this seeds with a liquid medium, resulting a naturally free gluten and lactose drink, inexpensive, easy to prepare, without synthetic additives aiming to contribute to food security, in terms of the provision of quality food, while causing a positive impact on the adult population, therefore, improving their quality of life from the nutritional, economic and social point of view.The nutritional composition, stability (pH and titratable acidity were evaluated using A.O.A.C Methodologies of. The acceptability of the product was carried out by means of an adapted panel (50 untrained judges). Data on organoleptic characteristics were collected. The established acceptance criteria were equal to or greater than 80%. The results showed a nutritional value of 8.5g of carbohydrates, 3.1g of protein, 0.4g of fat, and 0.25g of fiber for a daily serving of 200ml. Regarding storage stability (10 days, 5 ° C), the pH values varied 5.70 - 4.05, the titratable acidity showed increases from its initial value between 1.10 - 1.61 g citric acid / l of drink.We can conclude that the amaranth-based drink presented a good nutritional contribution, good stability at refrigeration temperature, a pleasant taste and a slightly vegetal smell, reflecting a positive appreciation of 92%.The appropriate sensory attributes reflecting a positive appreciation of this beverage by consumers. Keywords: nutrition, stability, acceptability, hydration