Simulation of Flow through a Miller Cuff Bypass Graft

Unnatural temporal and spatial distributions of wall shear stress in the anastomosis of distal bypass grafts have been identified as possible factors in the development of anastomotic intimal hyperplasia in these grafts. Distal bypass graft anastomoses with an autologus vein cuff (a Miller cuff) interposed between the graft and artery have been shown to alleviate the effects of intimal hyperplasia. In this study, pulsatile flow through models of a standard end-to-side anastomosis and a Miller cuff anastomosis are computed and the resulting wall shear stress and pressure distributions analysed. The results are inconclusive, and could be taken to suggest that the unnatural distributions of shear stress that do occur along the anastomosis floor may not be particularly important in the development of intimal hyperplasia. However, it seems more likely that the positive effects of the biological and material properties of the vein cuff, which are not considered in this study, somehow outweigh the negative effects of the shear stress distributions predicted to occur on the floor of the Miller-cuff graft.     

Circadian Variation in Cortisol Reactivity to an Acute Stressor

To investigate the role of the circadian pacemaker in cortisol reactivity to a cold pressor challenge, 26 diurnally subjects participated in a constant‐routine protocol and were divided into two groups. Group 1 started immediately after a monitored sleep period at 09:00 h, while group 2 started 12 h later. After 2 h of adaptation, a cold pressor test was presented every 3 h. The cortisol response was assessed by means of saliva samples that were taken before and after the test. The pretest samples were considered to be base‐rate measures and base‐rate values as subtracted from post‐test values were considered as reactivity measures. Both measures showed distinct Time‐of‐Day variations (respectively: F_7,168 = 16.92, p < 0.001, ε = 0.383; and F_7,175 = 8.01, p < 0.001, ε = 0.523). These findings are interpreted as evidence for the existence of an endogenous circadian periodicity underlying the sensitivity of the hypothalamus–pituitary–adrenal (HPA)‐axis to acute stress.     

Peroxynitrite,a Stealthy Biological Oxidant

Peroxynitrite is the product of the diffusion-controlled reaction of nitric oxide and superoxide radicals. Peroxynitrite, a reactive short-lived peroxide with a pK_a of 6.8, is a good oxidant and nucleophile. It also yields secondary free radical intermediates such as nitrogen dioxide and carbonate radicals. Much of nitric oxide- and superoxide-dependent cytotoxicity resides on peroxynitrite, which affects mitochondrial function and triggers cell death via oxidation and nitration reactions. Peroxynitrite is an endogenous toxicant but is also a cytotoxic effector against invading pathogens. The biological chemistry of peroxynitrite is modulated by endogenous antioxidant mechanisms and neutralized by synthetic compounds with peroxynitrite-scavenging capacity.     

SKN-1/Nrf,stress responses,and aging in Caenorhabditis elegans

The mammalian Nrf/CNC proteins (Nrf1, Nrf2, Nrf3, p45 NF-E2) perform a wide range of cellular protective and maintenance functions. The most thoroughly described of these proteins, Nrf2, is best known as a regulator of antioxidant and xenobiotic defense, but more recently has been implicated in additional functions that include proteostasis and metabolic regulation. In the nematode Caenorhabditis elegans, which offers many advantages for genetic analyses, the Nrf/CNC proteins are represented by their ortholog SKN-1. Although SKN-1 has diverged in aspects of how it binds DNA, it exhibits remarkable functional conservation with Nrf/CNC proteins in other species and regulates many of the same target gene families. C. elegans may therefore have considerable predictive value as a discovery model for understanding how mammalian Nrf/CNC proteins function and are regulated in vivo. Work in C. elegans indicates that SKN-1 regulation is surprisingly complex and is influenced by numerous growth, nutrient, and metabolic signals. SKN-1 is also involved in a wide range of homeostatic functions that extend well beyond the canonical Nrf2 function in responses to acute stress. Importantly, SKN-1 plays a central role in diverse genetic and pharmacologic interventions that promote C. elegans longevity, suggesting that mechanisms regulated by SKN-1 may be of conserved importance in aging. These C. elegans studies predict that mammalian Nrf/CNC protein functions and regulation may be similarly complex and that the proteins and processes that they regulate are likely to have a major influence on mammalian life- and healthspan.     

On the Use of Infinite Elements for the Determination of Optimal Closure Patterns based on Stress Analysis

Solid infinite elements are used in conjunction with finite elements to compute the stress and displacement distribution resulting from the suturing of wounds of symmetric and nonsymmetric shapes in orthotropic, abdominal human skin. The optimal pattern of suturing of wounds are investigated from a stress perspective. Highly accurate, quantitative and qualitative improvements over the use of finite elements to approximate distant boundaries are obtained. Numerical results quantitatively agree with analytic results computed using complex analysis techniques. The technique used and the results obtained will aid surgeons in closing nonsymmetrical wounds on regions of the body that exhibit orthotropy.     

Consequences of the reduction of the Photosystem II antenna size on the light acclimation capacity of Arabidopsis thaliana

In several systems, from plant's canopy to algal bioreactors, the decrease of the antenna size has been proposed as a strategy to increase the photosynthetic efficiency. However, still little is known about possible secondary effects of such modifications. This is particularly relevant because the modulation of the antenna size is one of the most important light acclimation responses in photosynthetic organisms. In our study, we used an Arabidopsis thaliana mutant (dLhcb2), which has a 60% decrease of Lhcb1 and Lhcb2, the two main components of the major Photosystem II antenna complex. We show that the mutant maintains the photosynthetic and photoprotective capacity of the Wild Type (WT) and adapts to different light conditions by remodelling its photosynthetic apparatus, but the regulatory mechanism differs from that of the WT. Surprisingly, it does not compensate for the decreased light-harvesting capacity by increasing other pigment-protein complexes. Instead, it lowers the ratio of the cytochrome b₆f and ATP synthase to the photosystems, regulating linear electron flow and maintaining the photosynthetic control at the level of these complexes as in the WT. We show that targeting the reduction of two specific antenna proteins, Lhcb1 and Lhcb2, represents a viable solution to obtain plants with a truncated antenna size, which still maintain the capacity to acclimate to different light conditions.     

Organ-distinctive changes in respiration rates of rice plants under nickel stress

Nickel (Ni) is an essential mineral element that may accumulate to toxic levels in soils due to anthropogenic activities. The growth of rice plants cultured hydroponically was severely impaired when Ni concentration was raised from 0.1 to 0.5 mM. However, the decrease in plant growth was not accompanied by any significant effect on respiration rates at the whole plant level. Short-term treatments of excised roots with 0.1–1.0 mM Ni did not result in any significant changes in respiration. However, long-term treatments of whole plants induced clear distinctive effects on shoots and roots. There was a significant decline in growth of these organs when the plants were cultured for 10 days at 0.5 mM Ni. Although no significant changes in respiration occurred in shoots, it was drastically reduced in roots. Ni withdrawal after 5 days’ treatment caused an increase in respiration in roots, but a decrease in shoots, despite the fact that stress alleviation induced a similar and significant increase in fresh weight of both organs. Our results point to organ-related differences in the distribution of the energy resulting from respiration under Ni stress.     

Modeling the hypothalamus–pituitary–adrenal system: homeostasis by interacting positive and negative feedback

The hypothalamus–pituitary–adrenal (HPA) system is closely related to stress and the restoration of homeostasis. This system is stimulated in the second half of the night, decreases its activity in the daytime, and reaches the homeostatic level during the late evening. In this paper, we derive and discuss a novel model for the HPA system. It is based on three simple rules that constitute a principle of homeostasis and include only the most substantive physiological elements. In contrast to other models, its main components include, apart from the conventional negative feedback ingredient, a positive feedback loop. To validate the model, we present a parameter estimation procedure that enables one to adapt the model to clinical observations. Using this methodology, we are able to show that the novel model is capable of simulating clinical trials. Furthermore, the stationary state of the system is investigated. We show that, under mild conditions, the system always has a well-defined set-point, which reflects the clinical situation to be modeled. Finally, the computed parameters may be interpreted from a physiological point of view, thereby leading to insights about diseases like depression, obesity, or diabetes.     

Characterization of a Mycobacterium tuberculosis Nanocompartment and Its Potential Cargo Proteins

Mycobacterium tuberculosis has evolved various mechanisms by which the bacterium can maintain homeostasis under numerous environmental assaults generated by the host immune response. M. tuberculosis harbors enzymes involved in the oxidative stress response that aid in survival during the production of reactive oxygen species in activated macrophages. Previous studies have shown that a dye-decolorizing peroxidase (DyP) is encapsulated by a bacterial nanocompartment, encapsulin (Enc), whereby packaged DyP interacts with Enc via a unique C-terminal extension. M. tuberculosis also harbors an encapsulin homolog (CFP-29, Mt-Enc), within an operon with M. tuberculosis DyP (Mt-DyP), which contains a C-terminal extension. Together these observations suggest that Mt-DyP interacts with Mt-Enc. Furthermore, it has been suggested that DyPs may function as either a heme-dependent peroxidase or a deferrochelatase. Like Mt-DyP, M. tuberculosis iron storage ferritin protein, Mt-BfrB, and an M. tuberculosis protein involved in folate biosynthesis, 7,8-dihydroneopterin aldolase (Mt-FolB), have C-terminal tails that could also interact with Mt-Enc. For the first time, we show by co-purification and electron microscopy that mycobacteria via Mt-Enc can encapsulate Mt-DyP, Mt-BfrB, and Mt-FolB. Functional studies of free or encapsulated proteins demonstrate that they retain their enzymatic activity within the Mt-Enc nanocompartment. Mt-DyP, Mt-FolB, and Mt-BfrB all have antioxidant properties, suggesting that if these proteins are encapsulated by Mt-Enc, then this nanocage may play a role in the M. tuberculosis oxidative stress response. This report provides initial structural and biochemical clues regarding the molecular mechanisms that utilize compartmentalization by which the mycobacterial cell may aid in detoxification of the local environment to ensure long term survival.