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The cover image depicts colonies derived from human epidermal stem cells (holoclones). Transgenic holoclones from a 7-year-old boy were used to reconstruct his damaged skin. A severe case of junctional epidermolysis bullosa, a genetic disorder in which the integrity of the skin is compromised, meant that much of the boyâs skin developed chronic blisters and wounds. In this weekâs issue, Michele De Luca and his colleagues describe how they approached the boyâs treatment. A viral vector was used to transduce stem cells derived from the patientâs skin with a functional version of the affected gene, in this case a mutated î3 chain of laminin-332. These stem cells were then used to grow large sheets of functional epidermis that could be used as surgical grafts to replace 80% of the boyâs skin. The research also provided insight into the generation of the epidermis and revealed that it is sustained by defined, long-lived stem cells. An accompanying News & Views piece explores the limitations and wider implications of the technique, including the potential of translational research to guide combinatorial stem-cell and gene therapies to treat otherwise incurable diseases. Cover image: Sergio Bondanza & Francesca La Mantia/Centre for Regenerative Medicine âStefano Ferrariâ & Holostem Terapie Avanzate
Modelling suggests that Pluto's atmospheric temperature is regulated by haze, unlike the other planetary bodies in the Solar System. The finding has implications for our understanding of exoplanetary atmospheres. See Letter p.352
Infection with Shigella flexneri bacteria is a major cause of infant death. It emerges that S. flexneri evades intracellular defences by releasing a protein that triggers the destruction of members of a key family of host enzymes. See Letter p.378
Microbial activity in the sea results in a loss of bioavailable nitrogen. It emerges that the climate phenomenon called the El Niño–Southern Oscillation has a surprisingly large effect on the size of this loss.
The treatment of a patient affected by an incurable genetic skin disease demonstrates the efficacy, feasibility and safety of replacing almost the whole skin using genetically corrected stem cells. See Letter p.327
The physical nature of two regions called large low-shear-velocity provinces at the base of Earth's mantle is uncertain. A measurement of their density has implications for our understanding of mantle dynamics. See Article p.321
Statistical analysis of data on threatened species provides a model that can predict how rates of investment in conservation affect biodiversity under changing human population levels and agricultural and economic conditions. See Letter p.364
A single antibody uses multiple antiviral mechanisms to block the replication of influenza B viruses in mice and ferrets. The development could inform research into improved flu vaccines.
An estimate of Earth’s deep-mantle buoyancy is derived from GPS-based measurements of body tide deformation and shown to be dominated by dense material possibly related to subducted oceanic plates or primordial rock.
Autologous transgenic epidermal stem cell cultures are used to reconstitute almost the entire epidermis of a patient with severe junctional epidermolysis bullosa.
Profiling of 53,193 individual epithelial cells from the mouse small intestine identifies previously unknown cell subtypes and corresponding gene markers, providing insight into gut homeostasis and response to pathogens.
IgA+ B cells expressing programmed death ligand 1 (PD-L1) and interleukin 10 accumulate in the inflamed livers of humans and mice with non-alcoholic fatty liver disease where they promote the progression to hepatocellular carcinoma by limiting the local activation of PD-1-expressing CD8+ T cells.
Single-molecule fluorescence resonance energy transfer is used to identify the rate-limiting step and new intermediates in the conformational cycle of the Listeria monocytogenes calcium transporter LMCA1.
Modelling results find that the temperature of Pluto’s atmosphere is regulated by haze particles rather than gas molecules, suggesting that Pluto should be brighter than previously thought at mid-infrared wavelengths.
Sufficiently strong modulation of the interaction strength in a Bose–Einstein condensate induces inelastic atom–atom scattering and causes collective emission of matter-wave jets from the condensate.
The relaxation dynamics of granular materials is more like that of complex fluids than that of thermal glass-forming systems, owing to the absence of the ‘cage effect’.
Empirical two-part models describe the relationship between conservation spending, human development pressures and biodiversity loss and can inform sustainable development strategies by predicting the effects of financing decisions on future biodiversity losses.
In European Neolithic populations, the arrival of farmers prompted admixture with local hunter-gatherers over many centuries, resulting in distinct signatures in each region due to a complex series of interactions.
In the mouse caudal brainstem, functionally distinct neuronal subpopulations, which are distinguishable by neurotransmitter identity, connectivity and location, regulate locomotion parameters.
A Shigella flexneri type III secretion system effector targets cellular proteins for degradation via the ubiquitin/proteasome pathway, suggesting that such effectors help to overcome defences against bacterial infection.
A signalling mechanism in human cells for sensing DNA damage induced by alkylation involves ubiquitin-dependent recruitment of the alkylation repair complex ASCC to the vicinity of the damage and co-localization with transcription and splicing factors.
Application of cryo-electron tomography and subtomogram averaging to determine the structure of the Ebola virus nucleocapsid within intact viruses and recombinant nucleocapsid-like assemblies.