A novel mechanism for activation of Aurora-A kinase by Ajuba

Aurora-A is a centrosome-localized serine/threonine kinase, which plays a critical role in mitotic and meiotic cell division processes. However, the regulation of Aurora-A is still not fully understood. Previously, we have found an intramolecular inhibitory regulation mechanism of Aurora-A: the N-terminal regulatory domain (aa 1–128, Nt) can interact with the C-terminal catalytic domain (aa 129–403, Cd) and inhibit the kinase activity of Aurora-A. In this study, we found that the PreLIM domain of Ajuba, another important activator of Aurora-A, induces the autophosphorylation of the C-terminal kinase domain of Aurora-A, and is phosphorylated by the C-terminal. Moreover, the LIM domain of Ajuba can competitively bind to the N-terminal of Aurora-A, and inhibited the interaction between N-terminal and C-terminal of Aurora A. Taken together, these results suggest a novel mechanism for regulation of Aurora-A by Ajuba.     

Suppressing mutation-induced protein aggregation in mammalian cells by mutating residues significantly displaced upon the original mutation

Mutations introduced to wild-type proteins naturally, or intentionally via protein engineering, often lead to protein aggregation. In particular, protein aggregation within mammalian cells has significant implications in the disease pathology and biologics production; making protein aggregation modulation within mammalian cells a very important engineering topic. Previously, we showed that the semi-rational design approach can be used to reduce the intracellular aggregation of a protein by recovering the conformational stability that was lowered by the mutation. However, this approach has limited utility when no rational design approach to enhance conformational stability is readily available. In order to overcome this limitation, we investigated whether the modification of residues significantly displaced upon the original mutation is an effective way to reduce protein aggregation in mammalian cells. As a model system, human copper, zinc superoxide dismutase mutant containing glycine to alanine mutation at position 93 (SOD1^G93A) was used. A panel of mutations was introduced into residues substantially displaced upon the G93A mutation. By using cell-based aggregation assays, we identified several novel variants of SOD1^G93A with reduced aggregation propensity within mammalian cells. Our findings successfully demonstrate that the aggregation of a mutant protein can be suppressed by mutating the residues significantly displaced upon the original mutation.     

Cardiac imaging: the biological effects of diagnostic cardiac ultrasound

Diagnostic cardiac ultrasounds are an environment-friendly and non-ionising imaging technology. However, ultrasounds are not biologically inert, and their use might have profound clinical impact. This paper summarizes the known effects of cardiac ultrasound—compared to other major imaging techniques—to exposed patients and to clinically exposed physicians practising ultrasound imaging. Furthermore, this review also provides an overview of the evidences on the biological effects of diagnostic ultrasound—which suggest that ultrasound with frequency, intensity and duration fully in the diagnostic range have significant molecular, cellular and organ effects.

A better understanding of these effects may improve our understanding of the complex interactions between ultrasound and biological tissues and may open new avenues to therapeutic applications based on the ultrasound-modulated cell functions, such as membrane transduction, apoptosis, cell permeability and thrombolysis.     

Intestinal caveolin-1 is important for dietary fatty acid absorption

How dietary fatty acids are absorbed into the enterocyte and transported to the ER is not established. We tested the possibility that caveolin-1 containing lipid rafts and endocytic vesicles were involved. Apical brush border membranes took up 15% of albumin bound ³H-oleate whereas brush border membranes from caveolin-1 KO mice took up only 1%. In brush border membranes, the ³H-oleate was in the detergent resistant fraction of an OptiPrep gradient. On OptiPrep gradients of intestinal cytosol, we also found the ³H-oleate in the detergent resistant fraction, separate from OptiPrep gradients spiked with ³H-oleate or ³H-triacylglycerol. Caveolin-1 immuno-depletion of cytosol removed 91% of absorbed ³H-oleate whereas immuno-depletion using IgG, or anti-caveolin-2 or -3 or anti-clathrin antibodies removed 20%. Electron microscopy showed the presence of caveolin-1 containing vesicles in WT mouse cytosol that were 4 fold increased by feeding intestinal sacs 1 mM oleate. No vesicles were seen in caveolin-1 KO mouse cytosol. Caveolin-1 KO mice gained less weight on a 23% fat diet and had increased fat in their stool compared to WT mice. We conclude that dietary fatty acids are absorbed by caveolae in enterocyte brush border membranes, are endocytosed, and transported in cytosol in caveolin-1 containing endocytic vesicles.     

Energy dissipation is an essential mechanism to sustain the viability of plants: The physiological limits of improved photosynthesis

In bright sunlight photosynthetic activity is limited by the enzymatic machinery of carbon dioxide assimilation. This supererogation of energy can be easily visualized by the significant increases of photosynthetic activity under high CO₂ conditions or other metabolic strategies which can increase the carbon flux from CO₂ to metabolic pools. However, even under optimal CO₂ conditions plants will provide much more NADPH + H⁺ and ATP that are required for the actual demand, yielding in a metabolic situation, in which no reducible NADP⁺ would be available. As a consequence, excited chlorophylls can activate oxygen to its singlet state or the photosynthetic electrons can be transferred to oxygen, producing highly active oxygen species such as the superoxide anion, hydroxyl radicals and hydrogen peroxide. All of them can initiate radical chain reactions which degrade proteins, pigments, lipids and nucleotides. Therefore, the plants have developed protection and repair mechanism to prevent photodamage and to maintain the physiological integrity of metabolic apparatus. The first protection wall is regulatory energy dissipation on the level of the photosynthetic primary reactions by the so-called non-photochemical quenching. This dissipative pathway is under the control of the proton gradient generated by the electron flow and the xanthophyll cycle. A second protection mechanism is the effective re-oxidation of the reduction equivalents by so-called “alternative electron cycling” which includes the water-water cycle, the photorespiration, the malate valve and the action of antioxidants. The third system of defence is the repair of damaged components. Therefore, plants do not suffer from energy shortage, but instead they have to invest in proteins and cellular components which protect the plants from potential damage by the supererogation of energy. Under this premise, our understanding and evaluation for certain energy dissipating processes such as non-photochemical quenching or photorespiration appear in a quite new perspective, especially when discussing strategies to improve the solar energy conversion into plant biomass.     

Contrast-enhancement cardiac magnetic resonance imaging beyond the scope of viability

The clinical applications of cardiovascular magnetic resonance imaging with contrast enhancement are expanding. Besides the direct visualisation of viable and non-viable myocardium, this technique is increasingly used in a variety of cardiac disorders to determine the exact aetiology, guide proper treatment, and predict outcome and prognosis. In this review, we discuss the value of cardiovascular magnetic resonance imaging with contrast enhancement in a range of cardiac disorders, in which this technique may provide insights beyond the scope of myocardial viability.     

Cross-correlations between gluteal muscle thickness derived from ultrasound imaging and hip biomechanics during walking gait

Ultrasound imaging (USI) of muscle thickness offers different insights into musculoskeletal function than kinematics, kinetics, and surface electromyography (sEMG), however it is unknown how USI-derived measures correlate to traditional measures during walking. The purpose of this study was to compare USI-derived gluteus maximus (GMAX) and medius (GMED) thickness measures to tri-planar hip kinematics and kinetics, and GMED thickness to sEMG amplitude. Fourteen females walked on a treadmill at 1.34 m/s. GMAX and GMED thickness, hip tri-planar kinematics, kinetics, and GMED sEMG were simultaneously recorded. USI-derived thickness measures were compared to other biomechanical outcomes using cross-correlation analyses, computed at each 1% (11-ms) of the gait cycle with lag times from −20% to 20%. GMED and GMAX thickness measures were most strongly correlated with hip extension and abduction angles at 150–220-ms lags (cross-correlation coefficients [CCF]: −0.34; −0.83). GMED thickness was most correlated to abduction and external rotation moments simultaneously (CCF: −0.28; −0.47). GMAX thickness and flexion moments were most strongly correlated at a 66-ms lag (CCF: 0.33). GMED sEMG amplitude was most strongly correlated to muscle thickness at a 99-ms lag (CCF: 0.39). These results elucidate the unique information provided from USI-derived measures of gluteal muscle thickness during walking.