A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials.

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Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection

Doitsh, Gilad; Galloway, Nicole L. K.; Geng, Xin; Yang, Zhiyuan; Monroe, Kathryn M.; Zepeda, Orlando; Hunt, Peter W.; Hatano, Hiroyu; Sowinski, Stefanie; Muñoz-Arias, Isa; Greene, Warner C.

2013 Nature

doi: 10.1038/nature12940pmid:

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Architecture of the large subunit of the mammalian mitochondrial ribosome

Greber, Basil J.; Boehringer, Daniel; Leitner, Alexander; Bieri, Philipp; Voigts-Hoffmann, Felix; Erzberger, Jan P.; Leibundgut, Marc; Aebersold, Ruedi; Ban, Nenad

2013 Nature

doi: 10.1038/nature12890pmid: 24362565

Mitochondrial ribosomes synthesize a number of highly hydrophobic proteins encoded on the genome of mitochondria, the organelles in eukaryotic cells that are responsible for energy conversion by oxidative phosphorylation. The ribosomes in mammalian mitochondria have undergone massive structural changes throughout their evolution, including ribosomal RNA shortening and acquisition of mitochondria-specific ribosomal proteins. Here we present the three-dimensional structure of the 39S large subunit of the porcine mitochondrial ribosome determined by cryo-electron microscopy at 4.9 Å resolution. The structure, combined with data from chemical crosslinking and mass spectrometry experiments, reveals the unique features of the 39S subunit at near-atomic resolution and provides detailed insight into the architecture of the polypeptide exit site. This region of the mitochondrial ribosome has been considerably remodelled compared to its bacterial counterpart, providing a specialized platform for the synthesis and membrane insertion of the highly hydrophobic protein components of the respiratory chain.

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Tunable symmetry breaking and helical edge transport in a graphene quantum spin Hall state

Young, A. F.; Sanchez-Yamagishi, J. D.; Hunt, B.; Choi, S. H.; Watanabe, K.; Taniguchi, T.; Ashoori, R. C.; Jarillo-Herrero, P.

2013 Nature

doi: 10.1038/nature12800pmid: 24362569

Applying a very large magnetic field to charge-neutral monolayer graphene produces a symmetry-protected quantum spin Hall state with helical edge states whose properties can be modulated by balancing the applied field against an intrinsic antiferromagnetic instability.

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Dislocations in bilayer graphene

Butz, Benjamin; Dolle, Christian; Niekiel, Florian; Weber, Konstantin; Waldmann, Daniel; Weber, Heiko B.; Meyer, Bernd; Spiecker, Erdmann

2013 Nature

doi: 10.1038/nature12780pmid: 24352231

Basal-plane dislocations, identified as fundamental defects in bilayer graphene by transmission electron microscopy and atomistic simulations, reveal striking size effects, most notably a pronounced buckling of the graphene membrane, which drastically alters the strain state and is of key importance for the material’s mechanical and electronic properties.

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The genome of the recently domesticated crop plant sugar beet (Beta vulgaris)

Dohm, Juliane C.; Minoche, André E.; Holtgräwe, Daniela; Capella-Gutiérrez, Salvador; Zakrzewski, Falk; Tafer, Hakim; Rupp, Oliver; Sörensen, Thomas Rosleff; Stracke, Ralf; Reinhardt, Richard; Goesmann, Alexander; Kraft, Thomas; Schulz, Britta; Stadler, Peter F.; Schmidt, Thomas; Gabaldón, Toni; Lehrach, Hans; Weisshaar, Bernd; Himmelbauer, Heinz

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Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease

Cruchaga, Carlos; Karch, Celeste M.; Jin, Sheng Chih; Benitez, Bruno A.; Cai, Yefei; Guerreiro, Rita; Harari, Oscar; Norton, Joanne; Budde, John; Bertelsen, Sarah; Jeng, Amanda T.; Cooper, Breanna; Skorupa, Tara; Carrell, David; Levitch, Denise; Hsu, Simon;

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Diet rapidly and reproducibly alters the human gut microbiome

David, Lawrence A.; Maurice, Corinne F.; Carmody, Rachel N.; Gootenberg, David B.; Button, Julie E.; Wolfe, Benjamin E.; Ling, Alisha V.; Devlin, A. Sloan; Varma, Yug; Fischbach, Michael A.; Biddinger, Sudha B.; Dutton, Rachel J.; Turnbaugh, Peter J.

2013 Nature

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Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated modification

Tessarz, Peter; Santos-Rosa, Helena; Robson, Sam C.; Sylvestersen, Kathrine B.; Nelson, Christopher J.; Nielsen, Michael L.; Kouzarides, Tony

2013 Nature

doi: 10.1038/nature12819pmid: 24352239

A description of a new histone modification, methylation of glutamine, on histone H2A in yeast and human cells.

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LitStream Collection

Structural basis of the alternating-access mechanism in a bile acid transporter

Zhou, Xiaoming; Levin, Elena J.; Pan, Yaping; McCoy, Jason G.; Sharma, Ruchika; Kloss, Brian; Bruni, Renato; Quick, Matthias; Zhou, Ming

2013 Nature

doi: 10.1038/nature12811pmid: 24317697

Inhibitors of the bile acid transporter ASBT may be useful therapeutics for treating hypercholesterolaemia and type 2 diabetes; here, two X-ray crystal structures of an ASBT homologue from Yersinia frederiksenii are solved.

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The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1β, are released. This death pathway thus links the two signature events in HIV infection—CD4 T-cell depletion and chronic inflammation—and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of ‘anti-AIDS’ therapeutics targeting the host rather than the virus.

2013 Nature

doi: 10.1038/nature12817pmid: 24352233

A full genome sequence is presented of sugar beet Beta vulgaris, the first plant belonging to Caryophyllales to have its genome sequenced; spinach was sequenced to enable inter-clade comparisons, and intraspecific variation was analysed by comparative genomics of a progenitor of all beet crops and additional sugar beet accessions.

Corcoran, Christopher D.;

Lorenzo-Betancor, Oswaldo;

Singleton, Andrew B.;

Hardy, John;

Kamboh, M. Ilyas;

St George-Hyslop, Peter;

2013 Nature

doi: 10.1038/nature12825pmid: 24336208

Whole-exome sequencing reveals that a rare variant of phospholipase D3 (PLD3(V232M)) segregates with Alzheimer’s disease status in two independent families and doubles risk for the disease in case–control series, and that several other PLD3 variants increase risk for Alzheimer’s disease in African Americans and people of European descent.

doi: 10.1038/nature12820pmid: 24336217

Consuming diets rich in plant versus animal products changes the microbes found in the human gut within days, with important implications for our health and evolution.