Volume 493 Issue 7434

Editorials

Twice the price p.577

Governments and funding agencies must do more to prevent the awarding of grants to research projects with significant overlap.

doi: 10.1038/493577a

Change for good p.577

The United States must boost energy spending to make its mark on the climate debate.

doi: 10.1038/493577b

Inflatable friends p.578

Research balloons have taught us much about the atmosphere, and could now fly into space.

doi: 10.1038/493578a

News

News Features

News & Views

Genetics: A social rearrangement p.612

Some worker fire ants will tolerate multiple queens in their colony, but others only one. It turns out that this behaviour is governed by a gene cluster on an unusual pair of chromosomes. Two scientists describe what these findings mean to the fields of social evolution, genetics and beyond. See Letter p.664

doi: 10.1038/nature11854

Solar physics: The planetary hypothesis revived p.613

The Sun's magnetic activity varies cyclically over a period of about 11 years. An analysis of a new, temporally extended proxy record of this activity hints at a possible planetary influence on the amplitude of the cycle.

doi: 10.1038/493613a

Structural biology: Spliceosome's core exposed p.615

The spliceosome complex removes intron sequences from RNA transcripts to form messenger RNA. The structure of a spliceosomal protein, Prp8, reveals the complex's active site and casts light on the origin of splicing. See Article p.638

doi: 10.1038/nature11857

Biogeochemistry: The depths of nitrogen cycling p.616

Breakdown of dissolved organic nitrogen in the ocean had been thought to be the preserve of microbes at the surface. The discovery that these microbes are not up to the task calls for a reassessment of the biogeochemistry of this nitrogen pool.

doi: 10.1038/493616a

Materials science: Synthetic polymers with biological rigidity p.618

Brush-like polymers with a rigidity similar to that of polymers in living cells have been synthesized and used to build force-responsive materials. The advance opens the door to applications in drug delivery and tissue engineering. See Letter p.651

doi: 10.1038/nature11855

Condensed-matter physics: Hidden is more p.619

Physicists have puzzled over a hidden electronic order in a uranium-based material for decades. A new theory attributes it to not just a single but a double breaking of time-reversal symmetry. See Article p.621

doi: 10.1038/493619a

Articles

Hastatic order in the heavy-fermion compound URu2Si2 p.621

The development of collective long-range order by means of phase transitions occurs by the spontaneous breaking of fundamental symmetries. Magnetism is a consequence of broken time-reversal symmetry, whereas superfluidity results from broken gauge invariance. The broken symmetry that develops below 17.5 kelvin in the heavy-fermion compound URu2Si2 has long eluded such identification. Here we show that the recent observation of Ising quasiparticles in URu2Si2 results from a spinor order parameter that breaks double time-reversal symmetry, mixing states of integer and half-integer spin. Such ‘hastatic’ order hybridizes uranium-atom conduction electrons with Ising 5f2 states to produce Ising quasiparticles; it accounts for the large entropy of condensation and the magnetic anomaly observed in torque magnetometry. Hastatic order predicts a tiny transverse moment in the conduction-electron ‘sea’, a colossal Ising anisotropy in the nonlinear susceptibility anomaly and a resonant, energy-dependent nematicity in the tunnelling density of states.

doi: 10.1038/nature11820

Towards germline gene therapy of inherited mitochondrial diseases p.627

Mutations in mitochondrial DNA (mtDNA) are associated with severe human diseases and are maternally inherited through the egg’s cytoplasm. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST; also called spindle–chromosomal complex transfer). Of 106 human oocytes donated for research, 65 were subjected to reciprocal ST and 33 served as controls. Fertilization rate in ST oocytes (73%) was similar to controls (75%); however, a significant portion of ST zygotes (52%) showed abnormal fertilization as determined by an irregular number of pronuclei. Among normally fertilized ST zygotes, blastocyst development (62%) and embryonic stem cell isolation (38%) rates were comparable to controls. All embryonic stem cell lines derived from ST zygotes had normal euploid karyotypes and contained exclusively donor mtDNA. The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing embryonic stem cells similar to controls.

doi: 10.1038/nature11647

Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants p.632

Mitochondrial DNA mutations transmitted maternally within the oocyte cytoplasm often cause life-threatening disorders. Here we explore the use of nuclear genome transfer between unfertilized oocytes of two donors to prevent the transmission of mitochondrial mutations. Nuclear genome transfer did not reduce developmental efficiency to the blastocyst stage, and genome integrity was maintained provided that spontaneous oocyte activation was avoided through the transfer of incompletely assembled spindle–chromosome complexes. Mitochondrial DNA transferred with the nuclear genome was initially detected at levels below 1%, decreasing in blastocysts and stem-cell lines to undetectable levels, and remained undetectable after passaging for more than one year, clonal expansion, differentiation into neurons, cardiomyocytes or β-cells, and after cellular reprogramming. Stem cells and differentiated cells had mitochondrial respiratory chain enzyme activities and oxygen consumption rates indistinguishable from controls. These results demonstrate the potential of nuclear genome transfer to prevent the transmission of mitochondrial disorders in humans.

doi: 10.1038/nature11800

Crystal structure of Prp8 reveals active site cavity of the spliceosome p.638

The active centre of the spliceosome consists of an intricate network formed by U5, U2 and U6 small nuclear RNAs, and a pre-messenger-RNA substrate. Prp8, a component of the U5 small nuclear ribonucleoprotein particle, crosslinks extensively with this RNA catalytic core. Here we present the crystal structure of yeast Prp8 (residues 885–2413) in complex with Aar2, a U5 small nuclear ribonucleoprotein particle assembly factor. The structure reveals tightly associated domains of Prp8 resembling a bacterial group II intron reverse transcriptase and a type II restriction endonuclease. Suppressors of splice-site mutations, and an intron branch-point crosslink, map to a large cavity formed by the reverse transcriptase thumb, and the endonuclease-like and RNaseH-like domains. This cavity is large enough to accommodate the catalytic core of group II intron RNA. The structure provides crucial insights into the architecture of the spliceosome active site, and reinforces the notion that nuclear pre-mRNA splicing and group II intron splicing have a common origin.

doi: 10.1038/nature11843

Letters

An old disk still capable of forming a planetary system p.644

In combination with existing observations and detailed circumstellar models, the detection of hydrogen deuteride emission from the star TW Hydrae implies a circumstellar disk mass of more than 0.05 solar masses, which is enough to form a planetary system like our own.

doi: 10.1038/nature11805

Responsive biomimetic networks from polyisocyanopeptide hydrogels p.651

Thermal transitions of polyisocyanide single molecules to polymer bundles and finally networks lead to hydrogels mimicking the properties of biopolymer intermediate-filament networks; their analysis shows that bundling and chain stiffness are crucial design parameters for hydrogels.

doi: 10.1038/nature11839

A Y-like social chromosome causes alternative colony organization in fire ants p.664

Fire ants (Solenopsis invicta) are socially polymorphic, with some workers tolerating several queens in their colony and others tolerating just one; this study shows that a non-recombining supergene is responsible for this social polymorphism, and the operation of this genomic region is remarkably similar to that of sex chromosomes.

doi: 10.1038/nature11832

Identification of small RNA pathway genes using patterns of phylogenetic conservation and divergence p.694

To identify comprehensively factors involved in RNAi and microRNA-mediated gene expression regulation, this study performed a phylogenetic analysis of 86 eukaryotic species; the candidates this approach highlighted were subjected to Bayesian analysis with transcriptional and proteomic interaction data, identifying protein orthologues of already known RNAi silencing factors, as well as other hits involved in splicing, suggesting a connection between the two processes.

doi: 10.1038/nature11779

The architecture of human general transcription factor TFIID core complex p.699

The structures of three distinct human transcription factor IID (TFIID) protein assemblies are solved using cryo-electron microscopy; by incorporating TAF8 and TAF10, the key structural changes that remodel TFIID during assembly are determined, particularly the transition from a symmetric core-TFIID to an asymmetric holo-complex.

doi: 10.1038/nature11791