Hot off the presses! Sep 16 Cell

The Sep 16 issue of the Cell is now up on Pubget (About Cell): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Human Evolutionary Genomics
  - Cell 146(6):847,849 (2011)
  The forces that have shaped the evolution of human genomes are now coming into sharp focus. This issue's Select explores recent discoveries that change our view of how our genomes became what they are—from the impact of interbreeding between ancient modern humans and Neanderthals to evidence that rates of de novo mutation may be subject to large variation between individuals.
• Molecular Mechanism of Protein Folding in the Cell
  - Cell 146(6):851-854 (2011)
  F.-Ulrich Hartl and Arthur Horwich will share this year's Lasker Basic Medical Science Award for the discovery of the cell's protein-folding machinery, exemplified by cage-like structures that convert newly synthesized proteins into their biologically active forms. Their fundamental findings reveal mechanisms that operate in normal physiologic processes and help to explain the problems that arise in diseases of protein folding.
• Artemisinin: Discovery from the Chinese Herbal Garden
  - Cell 146(6):855-858 (2011)
  This year's Lasker DeBakey Clinical Research Award goes to Youyou Tu for the discovery of artemisinin and its use in the treatment of malaria—a medical advance that has saved millions of lives across the globe, especially in the developing world.
• SIP-ing the Elixir of Youth
  - Cell 146(6):859-860 (2011)
  AMP-activated protein kinase (AMPK) is a conserved cellular fuel gauge previously implicated in aging. In this issue, describe how age-related deacetylation of Sip2, a subunit of the AMPK homolog in yeast, acts as a life span clock that can be wound backward or forward to modulate longevity.
• Basic and Therapeutic Aspects of Angiogenesis
  - Cell 146(6):873-887 (2011)
  Blood vessels form extensive networks that nurture all tissues in the body. Abnormal vessel growth and function are hallmarks of cancer and ischemic and inflammatory diseases, and they contribute to disease progression. Therapeutic approaches to block vascular supply have reached the clinic, but limited efficacy and resistance pose unresolved challenges. Recent insights establish how endothelial cells communicate with each other and with their environment to form a branched vascular network. The emerging principles of vascular growth provide exciting new perspectives, the translation of which might overcome the current limitations of pro- and antiangiogenic medicine.
• Selective Bypass of a Lagging Strand Roadblock by the Eukaryotic Replicative DNA Helicase
  - Cell 146(6):931-941 (2011)
  The eukaryotic replicative DNA helicase, CMG, unwinds DNA by an unknown mechanism. In some models, CMG encircles and translocates along one strand of DNA while excluding the other strand. In others, CMG encircles and translocates along duplex DNA. To distinguish between these models, replisomes were confronted with strand-specific DNA roadblocks in Xenopus egg extracts. An ssDNA translocase should stall at an obstruction on the translocation strand but not the excluded strand, whereas a dsDNA translocase should stall at obstructions on either strand. We found that replisomes bypass large roadblocks on the lagging strand template much more readily than on the leading strand template. Our results indicate that CMG is a 3′ to 5′ ssDNA translocase, consistent with unwinding via "steric exclusion." Given that MCM2-7 encircles dsDNA in G1, the data imply that formation of CMG in S phase involves remodeling of MCM2-7 from a dsDNA to a ssDNA binding mode.
• Wnt Regulates Spindle Asymmetry to Generate Asymmetric Nuclear β-Catenin in C. elegans
  - Cell 146(6):942-954 (2011)
  Extrinsic signals received by a cell can induce remodeling of the cytoskeleton, but the downstream effects of cytoskeletal changes on gene expression have not been well studied. Here, we show that during telophase of an asymmetric division in C. elegans, extrinsic Wnt signaling modulates spindle structures through APR-1/APC, which in turn promotes asymmetrical nuclear localization of WRM-1/β-catenin and POP-1/TCF. APR-1 that localized asymmetrically along the cortex established asymmetric distribution of astral microtubules, with more microtubules found on the anterior side. Perturbation of the Wnt signaling pathway altered this microtubule asymmetry and led to changes in nuclear WRM-1 asymmetry, gene expression, and cell-fate determination. Direct manipulation of spindle asymmetry by laser irradiation altered the asymmetric distribution of nuclear WRM-1. Moreover, laser manipulation of the spindles rescued defects in nuclear POP-1 asymmetry in wnt mutants. Our result! s reveal a mechanism in which the nuclear localization of proteins is regulated through the modulation of microtubules.
• Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells
  - Cell 146(6):1042 (2011)
  
• Synaptic PRG-1 Modulates Excitatory Transmission via Lipid Phosphate-Mediated Signaling
  - Cell 146(6):1043 (2011)