Multienzyme interactions of the de novo purine biosynthetic protein PAICS facilitate purinosome formation and metabolic channeling.

There is growing evidence that mammalian cells deploy a mitochondria-associated metabolon called the purinosome to perform channeled de novo purine biosynthesis (DNPB). However, the molecular mechanisms of this substrate-channeling pathway are not well defined. Here, we present molecular evidence of protein-protein interactions (PPIs) between the human bifunctional phosphoribosylaminoimidazole carboxylase/succinocarboxamide synthetase (PAICS) and other known DNPB enzymes.

Dynamics of embryonic stem cell differentiation inferred from single-cell transcriptomics show a series of transitions through discrete cell states.

The complexity of gene regulatory networks that lead multipotent cells to acquire different cell fates makes a quantitative understanding of differentiation challenging. Using a statistical framework to analyze single-cell transcriptomics data, we infer the gene expression dynamics of early mouse embryonic stem (mES) cell differentiation, uncovering discrete transitions across nine cell states. We validate the predicted transitions across discrete states using flow cytometry.

Pluripotency factors in embryonic stem cells regulate differentiation into germ layers.

Cell fate decisions are fundamental for development, but we do not know how transcriptional networks reorganize during the transition from a pluripotent to a differentiated cell state. Here, we asked how mouse embryonic stem cells (ESCs) leave the pluripotent state and choose between germ layer fates. By analyzing the dynamics of the transcriptional circuit that maintains pluripotency, we found that Oct4 and Sox2, proteins that maintain ESC identity, also orchestrate germ layer fate selection.

Glassy dynamics in thermally activated list sorting.

Sorting the integers 1 through N into an ordered list is a simple task that can be done rapidly. However, using an algorithm based on the thermally activated pairwise exchanges of neighboring list elements, we find sorting can display many features of a glass, even for lists as small as N=5. This includes memory and rejuvenation effects during aging-two hallmarks of glassy dynamics that have been difficult to reproduce in standard glass simulations.

Spectral responses in granular compaction.

The slow compaction of a tapped granular packing is reminiscent of the low-temperature dynamics glasses. Here, I study the dynamics of granular compaction by means of a volumetric spectroscopy. While the specific packing volume v displays glassy aging and memory effects at low tapping amplitudes Gamma, the dynamic volumetric susceptibility chi(v)= partial differentialv/ partial differentialGamma displays minimal glassy effects, and its frequency spectrum gives no indication of a rapidly growing time scale.

The packing of granular polymer chains.

Rigid particles pack into structures, such as sand dunes on the beach, whose overall stability is determined by the average number of contacts between particles. However, when packing spatially extended objects with flexible shapes, additional concepts must be invoked to understand the stability of the resulting structure. Here, we examine the disordered packing of chains constructed out of flexibly connected hard spheres.

Myelin figures: the buckling and flow of wet soap.

Myelin figures are interfacial structures formed when certain surfactants swell in excess water. Here, I present data and model calculations suggesting the formation and growth of myelins is due to the fluid flow of surfactant, driven by the hydration gradient at the dry surfactant/water interface; a simple model based on this idea qualitatively reproduces various myelin growth behaviors observed in different experiments. From a detailed experimental observation of how myelins develop from a planar precursor structure, I identify a mechanical instability that may underlie myelin formation.

Stability and growth of single myelin figures.

Myelin figures are long thin cylindrical structures that typically grow as a dense tangle when water is added to the concentrated lamellar phase of certain surfactants. We show that, starting from a well-ordered initial state, single myelin figures can be produced in isolation thus allowing a detailed study of their growth and stability. These structures grow with their base at the exposed edges of bilayer stacks from which material is transported into the myelin.