Direct evidence of the molecular basis for biological silicon transport

Diatoms are an important group of eukaryotic algae with a curious evolutionary innovation: they sheath themselves in a cell wall made largely of silica. The cellular machinery responsible for silicification includes a family of membrane permeases that recognize and actively transport the soluble precursor of biosilica, silicic acid. However, the molecular basis of silicic acid transport remains obscure. Here, we identify experimentally tractable diatom silicic acid transporter (SIT) homologues and study their structure and function in vitro, enabled by the development of a new fluorescence method for studying substrate transport kinetics. We show that recombinant SITs are Na(+)/silicic acid symporters with a 1:1 protein: substrate stoichiometry and K(M) for silicic acid of 20 μM. Protein mutagenesis supports the long-standing hypothesis that four conserved GXQ amino acid motifs are important in SIT function. This marks a step towards a detailed understanding of silicon transport with implications for biogeochemistry and bioinspired materials

Superfluid Flow Past an Array of Scatterers

We consider a model of nonlinear superfluid flow past a periodic array of point-like scatterers in one dimension. An application of this model is the determination of the critical current of a Josephson array in a regime appropriate to a Ginzburg-Landau formulation. Here, the array consists of short normal-metal regions, in the presence of a Hartree electron-electron interaction, and embedded within a one-dimensional superconducting wire near its critical temperature, $Tc$. We predict the critical current to depend linearly as $A (Tc-T)$, while the coefficient $A$ depends sensitively on the sizes of the superconducting and normal-metal regions and the strength and sign of the Hartree interaction. In the case of an attractive interaction, we find a further feature: the critical current vanishes linearly at some temperature $T*$ less than $Tc$, as well as at $Tc$ itself. We rule out a simple explanation for the zero value of the critical current, at this temperature $T*$, in terms of order parameter fluctuations at low frequencies.Comment: 23 pages, REVTEX, six eps-figures included; submitted to PR

Metabolism within the tumor microenvironment and its implication on cancer progression: an ongoing therapeutic target

Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment. Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the tumor microenvironment and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that tumor microenvironment is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with combined therapies including anti-tumor agents with those targeting stromal cell metabolism, anti-angiogenic drugs and/or immunotherapy are being developed as promising therapeutics.Mª Carmen Ocaña is recipient of a predoctoral FPU grant from the Spanish Ministry of Education, Culture and Sport. Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

Mechanism of antineoplastic activity of lonidamine

Lonidamine (LND) was initially introduced as an antispermatogenic agent. It was later found to have anticancer activity sensitizing tumors to chemo-, radio-, photodynamic-therapy and hyperthermia. Although the mechanism of action remained unclear, LND treatment has been known to target metabolic pathways in cancer cells. It has been reported to alter the bioenergetics of tumor cells by inhibiting glycolysis and mitochondrial respiration, while indirect evidence suggested that it also inhibited L-lactic acid efflux from cells mediated by members of the proton-linked monocarboxylate transporter (MCT) family and also pyruvate uptake into the mitochondria by the mitochondrial pyruvate carrier (MPC). Recent studies have demonstrated that LND potently inhibits MPC activity in isolated rat liver mitochondria (K(i) 2.5 μM) and cooperatively inhibits L-lactate transport by MCT1, MCT2 and MCT4 expressed in Xenopus laevis oocytes with K(0.5) and Hill Coefficient values of 36–40 μM and 1.65–1.85, respectively. In rat heart mitochondria LND inhibited the MPC with similar potency and uncoupled oxidation of pyruvate was inhibited more effectively (IC(50) ~7 μM) than other substrates including glutamate (IC(50) ~20 μM). LND inhibits the succinate-ubiquinone reductase activity of respiratory Complex II without fully blocking succinate dehydrogenase activity. LND also induces cellular reactive oxygen species through Complex II and has been reported to promote cell death by suppression of the pentose phosphate pathway, which resulted in inhibition of NADPH and glutathione generation. We conclude that MPC inhibition is the most sensitive anti-tumour target for LND, with additional inhibitory effects on MCT-mediated L-lactic acid efflux, Complex II and glutamine/glutamate oxidation

Particles-vortex interactions and flow visualization in He4

Recent experiments have demonstrated a remarkable progress in implementing and use of the Particle Image Velocimetry (PIV) and particle tracking techniques for the study of turbulence in He4. However, an interpretation of the experimental data in the superfluid phase requires understanding how the motion of tracer particles is affected by the two components, the viscous normal fluid and the inviscid superfluid. Of a particular importance is the problem of particle interactions with quantized vortex lines which may not only strongly affect the particle motion, but, under certain conditions, may even trap particles on quantized vortex cores. The article reviews recent theoretical, numerical, and experimental results in this rapidly developing area of research, putting critically together recent results, and solving apparent inconsistencies. Also discussed is a closely related technique of detection of quantized vortices negative ion bubbles in He4.Comment: To appear in the J Low Temperature Physic

Quantum turbulence in 4He, oscillating grids, and where do we go next?

Experimental approaches to the study of quantum turbulence (QT) in superfluid 4He in the low temperature limit, where the normal fluid density is effectively zero, are considered. A succinct general introduction covers liquid 4He, superfluidity, critical velocities for the onset of dissipation, quantized vortex lines and QT. The QT can be created mechanically by the oscillation of wires or grids above characteristic critical velocities. The interesting dynamics of the oscillating grid are discussed. It exhibits an enhanced effective mass due to backflow, as expected from classical hydrodynamics. It is found that the critical velocity attributable to the onset of QT production rises with increasing temperature. Oscillating objects like grids or wires create QT that is not well-characterized in terms of length scale, and the QT is not spatially homogeneous. The QT can be detected by the trapping of negative ions on vortex cores. Although the corresponding capture cross-section has not yet been measured, it is evidently very small, so that the technique cannot be expected to be a very sensitive one. In the future it is hoped to create well-characterized, homogeneous QT by means of a drawn grid. Improved sensitivity in the detection of QT is being sought through calorimetric techniques that monitor the temperature rise of the liquid caused by the decay of the vortex lines