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Alternative outlets for sustaining photosynthetic electron transport during dark-to-light transitions.
Environmental stresses dramatically impact the balance between the production of photosynthetically derived energetic electrons and Calvin-Benson-Bassham cycle (CBBC) activity; an imbalance promotes accumulation of reactive oxygen species and causes cell damage. Hence, photosynthetic organisms have developed several strategies to route electrons toward alternative outlets that allow for storage or harmless dissipation of their energy. In this work, we explore the activities of three essential outlets associated with Chlamydomonas reinhardtii photosynthetic electron transport: (i) reduction of O2 to H2O through flavodiiron proteins (FLVs) and (ii) plastid terminal oxidases (PTOX) and (iii) the synthesis of starch. Real-time measurements of O2 exchange have demonstrated that FLVs immediately engage during dark-to-light transitions, allowing electron transport when the CBBC is not fully activated. Under these conditions, we quantified maximal FLV activity and its overall capacity to direct photosynthetic electrons toward O2 reduction. However, when starch synthesis is compromised, a greater proportion of the electrons is directed toward O2 reduction through both the FLVs and PTOX, suggesting an important role for starch synthesis in priming/regulating CBBC and electron transport. Moreover, partitioning energized electrons between sustainable (starch; energetic electrons are recaptured) and nonsustainable (H2O; energetic electrons are not recaptured) outlets is part of the energy management strategy of photosynthetic organisms that allows them to cope with the fluctuating conditions encountered in nature. Finally, unmasking the repertoire and control of such energetic reactions offers new directions for rational redesign and optimization of photosynthesis to satisfy global demands for food and other resources
Clinical experience with lapatinib in patients with ErbB2-overexpressing metastatic breast cancer
A practical experiment to teach students continuous flow and physico-chemical methods: acetylation of ethylene diamine in liquid bi-phase
Despite growing applications being reported both in academia and industry, continuous flow chemistry remains a relatively untaught field across most chemistry undergraduate courses. This is particularly true in laboratory practical classes, where it is often deemed simpler to carry out synthetic reactions in traditional batch mode using round-bottomed flasks. Herein, we report the development of an undergraduate project that utilises cheap and readily available materials to construct continuous flow reactors. The students compare the performance of different types of reactors and conditions in a biphasic selective acetylation of a symmetrical diamine. Throughout the investigation, the students can vary multiple parameters as they optimise the reaction, thus actively learning and readjusting them based on their improved understanding. The experiments give the students an appreciation of continuous flow techniques in comparison to batch
A Hybridised Optimisation of an Automated Photochemical Continuous Flow Reactor
A new hybridized algorithm that combines process optimisation with response surface mapping was developed and applied in an automated continuous flow reaction. Moreover, a photochemical cascade CSTR was developed and characterised by chemical actinometry, showing photon flux density of ten times greater than previously reported in batch. The success of the algorithm was then evaluated in the aerobic oxidation of sp3 C–H bonds using benzophenone as photosensitizer in the newly developed photo reactor
Functional Locomotor Consequences of Uneven Forefeet for Trot Symmetry in Individual Riding Horses
ABSTRACT: Left-right symmetrical distal limb conformation can be an important prerequisite for a successful performance, and it is often hypothesized that asymmetric or uneven feet are important enhancing factors for the development of lameness. On a population level, it has been demonstrated that uneven footed horses are retiring earlier from elite level competition, but the biomechanical consequences are not yet known. The objectives of this study were to compare the functional locomotor asymmetries of horses with uneven to those with even feet. Hoof kinetics and distal limb kinematics were collected from horses (n = 34) at trot. Dorsal hoof wall angle was used to classify horses as even or uneven (1.5° difference between forefeet respectively) and individual feet as flat (55°). Functional kinetic parameters were compared between even and uneven forefeet using MANOVA followed by ANOVA. The relative influences of differences in hoof angle between the forefeet and of absolute hoof angle on functional parameters were analysed using multiple regression analysis (P<0.05). In horses with uneven feet, the side with the flatter foot showed a significantly larger maximal horizontal braking and vertical ground reaction force, a larger vertical fetlock displacement and a suppler fetlock spring. The foot with a steeper hoof angle was linearly correlated with an earlier braking-propulsion transition. The conformational differences between both forefeet were more important for loading characteristics than the individual foot conformation of each individual horse. The differences in vertical force and braking force between uneven forefeet could imply either an asymmetrical loading pattern without a pathological component or a subclinical lameness as a result of a pathological development in the steeper foot
C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins
An expanded GGGGCC repeat in C9orf72 is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. A fundamental question is whether toxicity is driven by the repeat RNA itself and/or by dipeptide repeat proteins generated by repeat-associated, non-ATG translation. To address this question we developed in vitro and in vivo models to dissect repeat RNA and dipeptide repeat protein toxicity. Expression of pure repeats in Drosophila caused adult-onset neurodegeneration attributable to poly-(glycine-arginine) proteins. Thus, expanded repeats promoted neurodegeneration through neurotoxic proteins. Expression of individual dipeptide repeat proteins with a non-GGGGCC RNA sequence showed both poly-(glycine-arginine) and poly-(proline-arginine) proteins caused neurodegeneration. These findings are consistent with a dual toxicity mechanism, whereby both arginine-rich proteins and repeat RNA contribute to C9orf72-mediated neurodegeneration
The effect of selective phosphodiesterase inhibitors, alone and in combination, on a murine model of allergic asthma
BACKGROUND: The anti-inflammatory effects of the selective phosphodiesterase (PDE) inhibitors cilostazol (PDE 3), RO 20-1724 (PDE 4) and sildenafil (PDE 5) were examined in a murine model of allergic asthma. These compounds were used alone and in combination to determine any potential synergism, with dexamethasone included as a positive control. METHODS: Control and ovalbumin sensitised Balb/C mice were administered orally with each of the possible combinations of drugs at a dose of 3 mg/Kg for 10 days. RESULTS: When used alone, RO 20-1724 significantly reduced eosinophil influx into lungs and lowered tumour necrosis factor-α, interleukin-4 and interleukin-5 levels in the bronchoalveolar lavage fluid when compared to untreated mice. Treatment with cilostazol or sildenafil did not significantly inhibit any markers of inflammation measured. Combining any of these PDE inhibitors produced no additive or synergistic effects. Indeed, the anti-inflammatory effects of RO 20-1724 were attenuated by co-administration of either cilostazol or sildenafil. CONCLUSIONS: These results suggest that concurrent treatment with a PDE 3 and/or PDE 5 inhibitor will reduce the anti-inflammatory effectiveness of a PDE 4 inhibitor
Self-Optimising Reactive Extractions: Towards the Efficient Development of Multi-Step Continuous Flow Processes
Downstream purification of products and intermediates is essential for the development of continuous flow processes. Described herein, is a study on the use of a modular and reconfigurable continuous flow platform for the self-optimisation of reactive extractions and multi-step reaction-extraction processes. The selective extraction of one amine from a mixture of two similar amines was achieved with an optimum separation of 90%, and in this case, the black-box optimisation approach was superior to global polynomial modelling. Furthermore, this methodology was utilised to simultaneously optimise the continuous flow synthesis and work-up of N-benzyl-α-methylbenzylamine with respect to four variables, resulting in a significantly improved purity
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