A Rho-GTPase based model explains group advantage in collective chemotaxis of neural crest cells.

A cluster of neural crest cells (NCCs) may chemotax up a shallow external gradient to which a single cell is unresponsive. To explain this intriguing 'group advantage', we propose a chemo-mechanical model based on the signaling proteins Rac1 and RhoA. We represent each cell as a polygon with nodes connected by elastic membranes.

A Rho-GTPase based model explains spontaneous collective migration of neural crest cell clusters.

We propose a model to explain the spontaneous collective migration of neural crest cells in the absence of an external gradient of chemoattractants. The model is based on the dynamical interaction between Rac1 and RhoA that is known to regulate the polarization, contact inhibition and co-attraction of neural crest cells. Coupling the reaction-diffusion equations for active and inactive Rac1 and RhoA on the cell membrane with a mechanical model for the overdamped motion of membrane vertices, we show that co-attraction and contact inhibition cooperate to produce persistence of polarity in a cluster of neural crest cells by suppressing the random onset of Rac1 hotspots that may mature into new protrusion fronts.

Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2.

Mitochondrial amidoxime reducing component (mARC) proteins are molybdopterin-containing enzymes of unclear physiological function. Both human isoforms mARC-1 and mARC-2 are able to catalyze the reduction of nitrite when they are in the reduced form. Moreover, our results indicate that mARC can generate nitric oxide (NO) from nitrite when forming an electron transfer chain with NADH, cytochrome b5, and NADH-dependent cytochrome b5 reductase.

Insights from molecular dynamics: the binding site of cocaine in the dopamine transporter and permeation pathways of substrates in the leucine and dopamine transporters.

The dopamine transporter (DAT) facilitates the regulation of synaptic neurotransmitter levels. As a target for therapeutic and illicit psycho-stimulant drugs like antidepressants and cocaine, DAT has been studied intensively. Despite a wealth of mutational and physiological data regarding DAT, the structure remains unsolved and details of the transport mechanism, binding sites and conformational changes remain debated.

Molecular distinctions between stasis and telomere attrition senescence barriers shown by long-term culture of normal human mammary epithelial cells.

Normal human epithelial cells in culture have generally shown a limited proliferative potential of approximately 10 to 40 population doublings before encountering a stress-associated senescence barrier (stasis) associated with elevated levels of cyclin-dependent kinase inhibitors p16 and/or p21. We now show that simple changes in medium composition can expand the proliferative potential of human mammary epithelial cells (HMEC) initiated as primary cultures to 50 to 60 population doublings followed by p16-positive, senescence-associated beta-galactosidase-positive stasis. We compared the properties of growing and senescent pre-stasis HMEC with growing and senescent post-selection HMEC, that is, cells grown in a serum-free medium that overcame stasis via silencing of p16 expression and that display senescence associated with telomere dysfunction.