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Grafted dermal fibroblasts (labelled green) shown supporting new hair follicle formation. Fibroblasts are unremarkable looking cells found in most tissues in the body, where they are mainly concerned with making the collagen that supports other cell types. The cells all look alike yet are functionally diverse, prompting the question, is there just one cell type responding differently to different stimuli, or do individual cells specialize? A transplantation and lineage tracing study in mice now shows that skin connective tissue arises from two distinct fibroblast lineages that also contribute differentially to skin development and repair after injury. One cell type forms the lower dermis and the other the upper dermis. The latter lineage is required for hair follicle production and is shown on the cover in green surrounding new hair follicles and contributing to the smooth muscles (red) that contract to make hair follicles stand on end. In wounded adult skin, the initial wave of dermal repair is mediated by the lower� lineage, which may explain the absence of hair follicles in newly closed wounds. The authors develop a comprehensive lineage tree for all fibroblast-derived cell types in mouse dermis, including smooth muscle cells and adipocytes. COVER: Ryan Driskell, Kings College London
Laboratory animals must have the very best standard of care if we are to justify their use in science. As one institution is found wanting, others should look to review their animal-welfare practices.
Evidence that long-term health is shaped by the environment in early life calls for prenatal interventions to tackle chronic disease, argue David Barker and colleagues.
Joe Letteri, Oscar-winning co-creator of Gollum on screen, looks at the evolution of computer animation as the next instalment of The Hobbit trilogy reaches cinemas.
An ultrafast mode of vesicle endocytosis — a crucial process occurring at neural junctions that underpins brain function — has been uncovered. Long-standing models of endocytosis will therefore need to be re-evaluated. See Article p.242
A three-dimensional climate model indicates that the fraction of Sun-like stars that might harbour a rocky planet within their habitable zone could be smaller than previously estimated. See Letter p.268
Mechanical stresses that are intrinsic to the early shape-forming movements of embryonic tissues have now been shown to play essential and evolutionarily conserved parts in cell-fate specification.
The status of the protein p53 determines whether inhibiting the cellular autophagy pathway promotes or inhibits pancreatic cancer in mice. This finding serves as a cautionary tale for clinical trials of autophagy inhibitors. See Letter p.296
The collective motions of dwarf galaxies in planes around the Andromeda galaxy and the Milky Way have presented a challenge to theory. Interactions between galaxy groups in the distant past may have left their imprint on these dwarfs.
Recent experience can affect memory either positively or negatively. A small population of inhibitory neurons that express the protein parvalbumin seems to have a pivotal role in this process. See Letter p.272
The idea of creating liquids containing magnetic particles that display ferromagnetism has not been realized — until now. Plate-shaped magnets in a liquid crystal have been made that exhibit this property. See Article p.237
Accumulating evidence that the eukaryotic nuclear lineage originated from within the Archaea provides support for a tree containing only two primary domains of life—the Achaea and Bacteria—over the currently accepted ‘three-domains tree’.
The idea that magnetic particles suspended in a liquid crystal might spontaneously orient into a ferromagnetic state has hitherto not been confirmed experimentally, but such a state has now been realized using nanometre-sized ferromagnetic platelets in a nematic liquid crystal.
Sustained neurotransmission requires recycling of synaptic vesicles, but the proposed mechanisms have been controversial; here a ‘flash-and-freeze’ method for electron microscopy reveals a new ultrafast form of endocytosis that is actin- and dynamin-dependent and occurs within 100 milliseconds of stimulation.
The lipid kinase phosphatidylinositol-4-OH kinase (PI(4)K) is identified as a target of the imidazopyrazines, a new antimalarial compound class that can inhibit several Plasmodium species at each stage of the parasite life cycle; the imidazopyrazines exert their inhibitory action by interacting with the ATP-binding pocket of PI(4)K.
Crystallographic structural analysis of bound states of the GBR1 and GBR2 subunits of human GABAB receptor shows that both subunits adopt an open conformation at rest — represented by the apo and antagonist-bound structures — and that only GBR1 closes in the activated state — represented by the agonist-bound structure.
Doppler-shifted X-ray emission lines from highly-ionized atoms, appearing together with radio emission from the relativistic jets of the black-hole candidate X-ray binary 4U 1630-47, indicate that the X-ray emission lines arise in a jet travelling at approximately two-thirds the speed of light and imply that the jet contains baryons.
An exactly solvable information-theoretical model of communications with a fully quantum electromagnetic field yields explicit expressions for all point-to-point capacities—the maximum possible rates of data transmission—of noisy quantum channels, with implications for quantum key distribution and fibre-optic communications.
A three-dimensional global climate model shows that the loss of a planet’s oceans through complete vaporization or evaporative escape to space will occur at considerably higher insolation than previously thought, owing to stabilizing atmospheric effects.
In adult mouse hippocampus, a learning-associated plasticity mechanism may exist that depends on the configuration of parvalbumin(PV)-expressing basket cell networks; trial and error learning initially promotes a higher fraction of cells with low PV expression, whereas learning completion promotes a higher fraction of cells with high PV expression, and these opposite configurations modulate learning and the underlying structural plasticity.
Fibroblasts constitute the major mesenchymal cell type in the connective tissue and their functions are remarkably diverse: here, by characterising lineages of mouse skin fibroblasts, it is shown that distinct subpopulations contribute to skin development and repair during injury.
It is known that human embryonic stem (ES) cells are more similar to mouse primed epiblast stem cells than to naive mouse ES cells; here culture conditions are determined that allow human ES and induced pluripotent stem cells to acquire a pluripotent state that retains growth characteristics highly similar to mouse naive ES cells, and competence in generating cross-species human-mouse embryonic chimaerism.
Growth of a flagellum outside the bacterial cell proceeds by successive subunit acquisition from the cell export machinery to form a chain that is pulled to the flagellum tip, where subunit crystallization provides the entropic force to drive the process.
Mitophagy is the elimination of damaged mitochondria by the autophagosome regulated by the ubiquitin ligase, parkin and the kinase PINK1; a genome-wide RNAi screen with high-content microscopy has identified new genes that have an upstream role in parkin translocation to the mitochondria.
In a mouse model of pancreatic tumours driven by Kras mutations, the outcome of suppressing autophagy is shown to depend on the status of p53: if p53 is intact, deletion of key autophagy genes blocks the progression of pre-cancerous lesions to aggressive carcinomas; however, in the absence of p53, loss of autophagy accelerates tumorigenesis, accompanied by deregulation of cancer cell metabolism.
The crystal structure of an archaeal Rce1 protein has been determined; this protein represents a novel type of intramembrane protease, with a distinct architecture and catalytic site.
A chromatin interaction analysis with paired-end tagging (ChIA-PET) approach is used to delineate chromatin interactions mediated by RNA polymerase II in several different stem-cell populations; putative long-range promoter–enhancer interactions are inferred, indicating that linear juxtaposition does not necessarily guide enhancer target selection and prevalent cell-specific enhancer usage.
Primary cilia are known as specialized calcium signalling compartments on the cell surface, but the ionic permeability and other physiological properties of these protrusions are unknown—this is one of two studies identifying the ion channels that densely populate primary cilia, with direct measurements revealing cilia as a unique, functionally independent calcium signalling compartment that modulates hedgehog signalling pathways.
Primary cilia are known as specialized calcium signalling compartments on the cell surface, but the ionic permeability and other physiological properties of these protrusions are unknown—this is one of two studies identifying the ion channels that densely populate primary cilia, with direct measurements revealing cilia as a unique, functionally independent calcium signalling compartment that modulates hedgehog signalling pathways.