TU Tau B: The Peculiar 'Eclipse' of a possible proto-Barium Giant

TU Tau (= HD 38218 = HIP 27135) is a binary system consisting of a C-N carbon star primary and an A-type secondary. We report on new photometry and spectroscopy which tracked the recent disappearance of the A-star secondary. The dimming of the A-star was gradual and irregular, with one or more brief brightenings, implying the presence of nonhomogeneities in the carbon star outflow. We also present evidence that the A-star is actively accreting s-process enriched material from the carbon star and suggest that it will therefore eventually evolve into a Barium giant. This is an important system as well because the A-type star can serve as a probe of the outer atmosphere of the carbon star.Comment: 9 pages, 9 figures, 4 tables, a number of amateur observatories made significant contributions to this research. Paper accepted for publication in The Astronomical Journa

A unifying model for mTORC1-mediated regulation of mRNA translation

he mTOR complex 1 (mTORC1) kinase nucleates a pathway that promotes cell growth and proliferation and is the target of rapamycin, a drug with many clinical uses. mTORC1 regulates messenger RNA translation, but the overall translational program is poorly defined and no unifying model exists to explain how mTORC1 differentially controls the translation of specific mRNAs. Here we use high-resolution transcriptome-scale ribosome profiling to monitor translation in mouse cells acutely treated with the mTOR inhibitor Torin 1, which, unlike rapamycin, fully inhibits mTORC1. Our data reveal a surprisingly simple model of the mRNA features and mechanisms that confer mTORC1-dependent translation control. The subset of mRNAs that are specifically regulated by mTORC1 consists almost entirely of transcripts with established 5′ terminal oligopyrimidine (TOP) motifs, or, like Hsp90ab1 and Ybx1, with previously unrecognized TOP or related TOP-like motifs that we identified. We find no evidence to support proposals that mTORC1 preferentially regulates mRNAs with increased 5′ untranslated region length or complexity. mTORC1 phosphorylates a myriad of translational regulators, but how it controls TOP mRNA translation is unknown. Remarkably, loss of just the 4E-BP family of translational repressors, arguably the best characterized mTORC1 substrates, is sufficient to render TOP and TOP-like mRNA translation resistant to Torin 1. The 4E-BPs inhibit translation initiation by interfering with the interaction between the cap-binding protein eIF4E and eIF4G1. Loss of this interaction diminishes the capacity of eIF4E to bind TOP and TOP-like mRNAs much more than other mRNAs, explaining why mTOR inhibition selectively suppresses their translation. Our results clarify the translational program controlled by mTORC1 and identify 4E-BPs and eIF4G1 as its master effectors.National Institutes of Health (U.S.) (Grant CA103866)National Institutes of Health (U.S.) (Grant CA129105)United States. Dept. of Defense (Grant W81XWH-07-0448)W. M. Keck FoundationLAM FoundationNational Science Foundation (U.S.). Graduate Research Fellowship Progra

Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma

Follicular lymphoma is an incurable B cell malignancy characterized by the t(14;18) translocation and mutations affecting the epigenome. Although frequent gene mutations in key signaling pathways, including JAK-STAT, NOTCH and NF-?B, have also been defined, the spectrum of these mutations typically overlaps with that in the closely related diffuse large B cell lymphoma (DLBCL). Using a combination of discovery exome and extended targeted sequencing, we identified recurrent somatic mutations in RRAGC uniquely enriched in patients with follicular lymphoma (17%). More than half of the mutations preferentially co-occurred with mutations in ATP6V1B2 and ATP6AP1, which encode components of the vacuolar H(+)-ATP ATPase (V-ATPase) known to be necessary for amino acid-induced activation of mTORC1. The RagC variants increased raptor binding while rendering mTORC1 signaling resistant to amino acid deprivation. The activating nature of the RRAGC mutations, their existence in the dominant clone and their stability during disease progression support their potential as an excellent candidate for therapeutic targeting