ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

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Highlights? Mouse pluripotent cells reprogram human B cells in heterokaryons ? ESCs lacking PRC1 or PRC2 cannot successfully reprogram ? Failure of PRC1/2-deficient ESCs to reprogram is functionally dominant ? PRC1/2 play a critical role in the chromatin reorganization required for reprogramming     

Keeping cell identity in Arabidopsis requires PRC1 RING-finger homologs that catalyze H2A monoubiquitination

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Highlights? AtBMI1A/B proteins prevent misexpression of embryonic traits in somatic cells ? PRC2 and AtBMI1A/B proteins maintain cells in their differentiated state ? AtBMI1A/B proteins mediate H2A monoubiquitination     

Impaired Cholesterol Efflux in Senescent Macrophages Promotes Age-Related Macular Degeneration

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Highlights? Macrophage senescence impairs cholesterol efflux and promotes macular degeneration ? Senescent macrophages polarize to a proangiogenic, disease-promoting phenotype ? Macrophage cholesterol efflux is regulated by miR33 and its target ABCA1 ? Age-related decrease in macrophage cholesterol efflux is therapeutically reversible     

Evidence for Geomagnetic Imprinting as a Homing Mechanism in Pacific Salmon

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Highlights? Sockeye salmon use geomagnetic imprinting as a homing mechanism ? The homing route of salmon is predicted by magnetic field drift (secular variation)     

Protein model discrimination using mutational sensitivity derived from deep sequencing

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Highlights? Individual mutant phenotypes in a saturation library derived via deep sequencing ? Residue depth and active-site residue derivation from mutant phenotypes ? Mutant-phenotype-derived parameters used for protein model discrimination ? Derivation of sequence-structure-function relationships without protein isolation     

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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Highlights? Smad-interacting protein 1 (SIP1) regulates hESC differentiation ? SIP1 upregulation promotes neuroectodermal differentiation ? SIP1 inhibits mesendodermal and endodermal differentiation ? SMAD2/3 and NANOG/OCT4/SOX2 cooperatively regulate SIP1 expression     

Two Deubiquitylases Act on Mitofusin and Regulate Mitochondrial Fusion along Independent Pathways

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Highlights? Mitochondrial fusion is regulated by independent ubiquitylation pathways ? The deubiquitylase Ubp2 promotes fusion, whereas Ubp12 inhibits fusion events ? Self-assembly and ubiquitylation cooperatively enable mitochondrial fusion ? Yeast mitofusin is sequentially ubiquitylated     

The Retroviral Restriction Ability of SAMHD1, but Not Its Deoxynucleotide Triphosphohydrolase Activity,Is Regulated by Phosphorylation

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Highlights? SAMHD1 only exhibits antiviral activity when expressed in noncycling cells ? SAMHD1 is unphosphorylated in noncycling cells ? Reverse genetics revealed that phosphorylated SAMHD1 is repressive for restriction ? SAMHD1 phosphorylation regulates restriction, but not the cellular levels of dNTPs     

The CDK9 Tail Determines the Reaction Pathway of Positive Transcription Elongation Factor b

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Highlights? The CDK9 C-terminal tail is important for the catalytic mechanism ? CDK9 phosphorylates the CTD in a nonprocessive manner ? The CDK9 tail folds over the ATP binding site during the catalytic cycle     

Design of a Phosphorylatable PDZ Domain with Peptide-Specific Affinity Changes

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Highlights? Successful design of phosphorylation sites into a globular protein ? Redesigned PDZ domain phosphorylation is associated with local destabilization ? Phosphorylation switches peptide binding function ? Phosphorylation switches peptide recognition specificity     

The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a SOUBA domain

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Highlights? ESCRT-I subunit UBAP1 is essential for degradation of antiviral protein tetherin ? UBAP1 has a domain consisting of a solenoid of overlapping UBAs (SOUBA) ? Each of the three UBAs in the SOUBA binds monoubiquitin     

piRNA-Triggered MIWI Ubiquitination and Removal by APC/C in Late Spermatogenesis

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Highlights? MIWI is a substrate of APC/C, and piRNA loading is essential for MIWI ubiquitination ? piRNA loading promotes MIWI binding to the APC/C substrate-binding subunit ? MIWI and piRNAs are coordinately eliminated in late spermatids ? Inhibition of MIWI destruction in late spermatids prevents sperm maturation     

MicroRNA-9 Coordinates Proliferation and Migration of Human Embryonic Stem Cell-Derived Neural Progenitors

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Highlights? miR-9 is expressed in hESC-derived early hNPCs and their progeny ? Loss of miR-9 inhibits early hNPC proliferation and delays maturation ? miR-9 knockdown promotes hNPC migration in vitro and in vivo ? Stathmin is a target of miR-9 and mediates its effects in early hNPCs     

Tremor Suppression by Rhythmic Transcranial Current Stimulation

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Highlights? Phase-cancelling cortical stimulation attenuates Parkinsonian tremor ? Prolonged stimulation may invoke adaptive mechanisms ? Phase cancellation may provide a generic treatment approach to oscillopathies ? TACS provides a convenient probe of cortical circuit dynamics in humans     

Structure of the Essential Diversity-Generating Retroelement Protein bAvd and Its Functionally Important Interaction with Reverse Transcriptase

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Highlights? bAvd forms a highly positively charged pentameric barrel ? bAvd binds both DNA and RNA, but without sequence preference ? The coding sequence for bAvd serves dual purposes ? The interaction of bAvd with bRT is likely to be important for retrohoming     

Allosteric Mechanism Controls Traffic in the Chaperone/Usher Pathway

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Highlights? Allosteric mechanism controls traffic in the chaperone/usher pathway ? Usher-binding site in free chaperone is conformationally locked ? Subunit binding opens the lock in the chaperone, allowing usher targeting     

The WW Domain Protein Kibra Acts Upstream of Hippo in Drosophila

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Highlights? The WW domain protein Kibra is a Hippo signalling component ? Kibra restricts organ size via Yorkie and acts upstream of Hippo and Merlin ? Kibra synergizes with Expanded and binds to Merlin     

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

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Highlights? Perivascular niche nitric oxide activates Notch in PDGF-induced gliomas ? Notch signaling drives tumor stem-like characteristics and reduces survival ? Loss of eNOS activity decreases tumor stem-like characteristics ? Suppressing eNOS activity prolongs survival in glioma-bearing mice