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Keller A
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Is conscious content available only to the skeletal muscle system?
BEHAVIORAL AND BRAIN SCIENCES 2016; 39(?):? Article e183
I applaud Morsella et al.'s approach to investigate consciousness in terms of behavioral control. After all, the function of the brain is to control behavior, and consciousness contributes to the function of the brain. However, I question whether conscious content is available only to the skeletal muscle system, as the principle of parallel responses into skeletal muscle (PRISM) (Morsella 2005) proposes.
Holt PR
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Curcumin for Inflammatory Bowel Disease: A Caution
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2016 JAN; 14(1):168-168
Yao NNY, O'Donnell ME
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Evolution of replication machines
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY 2016; 51(3):135-149
The machines that decode and regulate genetic information require the translation, transcription and replication pathways essential to all living cells. Thus, it might be expected that all cells share the same basic machinery for these pathways that were inherited from the primordial ancestor cell from which they evolved. A clear example of this is found in the translation machinery that converts RNA sequence to protein. The translation process requires numerous structural and catalytic RNAs and proteins, the central factors of which are homologous in all three domains of life, bacteria, archaea and eukarya. Likewise, the central actor in transcription, RNA polymerase, shows homology among the catalytic subunits in bacteria, archaea and eukarya. In contrast, while some "gears" of the genome replication machinery are homologous in all domains of life, most components of the replication machine appear to be unrelated between bacteria and those of archaea and eukarya. This review will compare and contrast the central proteins of the "replisome" machines that duplicate DNA in bacteria, archaea and eukarya, with an eye to understanding the issues surrounding the evolution of the DNA replication apparatus.
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Ferbel T, Galanti M, Garcia-Bellido A, Goldenzweig P, Han J, Harel A, Hindrichs O, Khukhunaishvili A, Petrillo G, Verzetti M, Demortier L, Arora S, Barker A, Chou JP, Contreras-Campana C, Contreras-Campana E, Duggan D, Ferencek D, Gershtein Y, Gray R, Halkiadakis E, Hidas D, Hughes E, Kaplan S, Elayavalli RK, Lath A, Panwalkar S, Park M, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Foerster M, Riley G, Rose K, Spanier S, York A, Bouhali O, Hernandez AC, Dalchenko M, De Mattia M, Delgado A, Dildick S, Eusebi R, Flanagan W, Gilmore J, Kamon T, Krutelyov V, Krutelyov V, Montalvo R, Mueller R, Osipenkov I, Pakhotin Y, Patel R, Perloff A, Roe J, Rose A, Safonov A, Tatarinov A, Ulmer KA, Akchurin N, Cowden C, Damgov J, Dragoiu C, Dudero PR, Faulkner J, Kunori S, Lamichhane K, Lee SW, Libeiro T, Undleeb S, Volobouev I, Appelt E, Delannoy AG, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Mao Y, Melo A, Sheldon P, Snook B, Tuo S, Velkovska J, Xu Q, Arenton MW, Boutle S, Cox B, Francis B, Goodell J, Hirosky R, Ledovskoy A, Li H, Lin C, Neu C, Wolfe E, Wood J, Xia F, Clarke C, Harr R, Karchin PE, Don CKK, Lamichhane P, Sturdy J, Belknap DA, Carlsmith D, Cepeda M, Christian A, Dasu S, Dodd L, Duric S, Friis E, Gomber B, Hall-Wilton R, Herndon M, Herve A, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Mohapatra A, Ojalvo I, Perry T, Pierro GA, Polese G, Ross I, Ruggles T, Sarangi T, Savin A, Sharma A, Smith N, Smith WH, Taylor D, Woods N
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Measurement of differential cross sections for Higgs boson production in the diphoton decay channel in pp collisions at root s=8TeV
EUROPEAN PHYSICAL JOURNAL C 2016 JAN 11; 76(1):? Article 13
A measurement is presented of differential cross sections for Higgs boson (H) production in pp collisions at root s = 8 TeV. The analysis exploits the H -> gamma gamma decay in data corresponding to an integrated luminosity of 19.7 fb(-1) collected by the CMS experiment at the LHC. The cross section is measured as a function of the kinematic properties of the diphoton system and of the associated jets. Results corrected for detector effects are compared with predictions at next-to-leading order and next-to-next-to-leading order in perturbative quantum chromodynamics, as well as with predictions beyond the standard model. For isolated photons with pseudorapidities vertical bar eta vertical bar < 2.5, and with the photon of largest and next-to-largest transverse momentum (p(T)(gamma)) divided by the diphoton mass m(gamma gamma) satisfying the respective conditions of p(T)(gamma)/m(gamma gamma) > 1/3 and > 1/4, the total fiducial cross section is 32 +/- 10 fb.
Wan BB, Hang LE, Zhao XL
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Multi-BRCT scaffolds use distinct strategies to support genome maintenance
CELL CYCLE 2016; 15(19):2561-2570
Genome maintenance requires coordinated actions of diverse DNA metabolism processes. Scaffolding proteins, such as those containing multiple BRCT domains, can influence these processes by collaborating with numerous partners. The best-studied examples of multi-BRCT scaffolds are the budding yeast Dpb11 and its homologues in other organisms, which regulate DNA replication, repair, and damage checkpoints. Recent studies have shed light on another group of multi-BRCT scaffolds, including Rtt107 in budding yeast and related proteins in other organisms. These proteins also influence several DNA metabolism pathways, though they use strategies unlike those employed by the Dpb11 family of proteins. Yet, at the same time, these 2 classes of multi-BRCT proteins can collaborate under specific situations. This review summarizes recent advances in our understanding of how these multi-BRCT proteins function in distinct manners and how they collaborate, with a focus on Dpb11 and Rtt107.
See SK, Hoogendoorn S, Chung AH, Ye F, Steinman JB, Sakata-Kato T, Miller RM, Cupido T, Zalyte R, Carter AP, Nachury MV, Kapoor TM, Chen JK
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Cytoplasmic Dynein Antagonists with Improved Potency and Isoform Selectivity
ACS CHEMICAL BIOLOGY 2016 JAN; 11(1):53-60
Cytoplasmic dyneins 1 and 2 are related members of the AAA+ superfamily (ATPases associated with diverse cellular activities) that function as the predominant minus-end-directed microtubule motors in eukaryotic cells. Dynein 1 controls mitotic spindle assembly, organelle movement, axonal transport, and other cytosolic, microtubule-guided processes, whereas dynein 2 mediates retrograde trafficking within motile and primary cilia. Small-molecule inhibitors are important tools for investigating motor protein-dependent mechanisms, and ciliobrevins were recently discovered as the first dynein-specific chemical antagonists. Here, we demonstrate that ciliobrevins directly target the heavy chains of both dynein isoforms and explore the structureactivity landscape of these inhibitors in vitro and in cells. In addition to identifying chemical motifs that are essential for dynein blockade, we have discovered analogs with increased potency and dynein 2 selectivity. These antagonists effectively disrupt Hedgehog signaling, intraflagellar transport, and ciliogenesis, making them useful probes of these and other cytoplasmic dynein 2-dependent cellular processes.
Roberts WM, Augustine SB, Lawton KJ, Lindsay TH, Thiele TR, Izquierdo EJ, Faumont S, Lindsay RA, Britton MC, Pokala N, Bergmann CI, Lockery SR
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A stochastic neuronal model predicts random search behaviors at multiple spatial scales in C. elegans
ELIFE 2016 JAN 29; 5(?):? Article e12572
Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the nematode Caenorhabditis elegans, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the C. elegans connectome and fit to a large-scale kinematic analysis of C. elegans behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in C. elegans can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding C. elegans locomotion and a testable neuronal model of random search that can be applied to other organisms.
Ge YJ, Zhang L, Nikolova M, Reva B, Fuchs E
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Strand-specific in vivo screen of cancer-associated miRNAs unveils a role for miR-21*in SCC progression
NATURE CELL BIOLOGY 2016 JAN; 18(1):111-121
MicroRNAs play diverse roles in both normal and malignant stem cells. Focusing on miRs and/or miR*s abundant in squamous cell carcinoma (SCC) stem cells, we engineer an efficient, strand-specific expression library, and apply functional genomics screening in mice to identify which of 169 cancer-associated miRs are key drivers in malignant progression. Not previously linked functionally to cancer, miR-21* was the second top hit, surfacing in >12% of tumours. miR-21* also correlates with poor prognosis in human SCCs and enhances tumour progression in xenografts. On deleting the miR-21 gene and rescuing each strand separately, we document the dual, but independent, oncogenicity of miR-21 and miR-21*. A cohort of predicted miR-21* targets inversely correlate with miR-21* in SCCs. Of particular interest is Phactr4, which we show is a miR-21* target in SCCs, acting through the Rb/E2F cell cycle axis. Through in vivo physiological miR screens, our findings add an interesting twist to an increasingly important oncomiR locus.
Seligman SJ, Casanova JL
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Yellow fever vaccine: worthy friend or stealthy foe?
EXPERT REVIEW OF VACCINES 2016; 15(6):681-691
Recognition that the live yellow fever vaccine may rarely be associated with viscerotropic disease (YEL-AVD) has diminished its safety status. However, the vaccine remains the principal tool for limiting the occurrence of yellow fever, making large portions of Africa and South America more habitable. The subject has previously been exhaustively reviewed. Novel concepts in the current report include the description of a systematic method for deciding whom to vaccinate, recommendations for obtaining data helpful in making that decision, and suggestions for additional study. The vaccine is indeed a worthy friend, but its adverse reactions need to be recognized.
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Search for the production of an excited bottom quark decaying to tW in proton-proton collisions at root s=8 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2016 JAN 27; ?(1):? Article 166
A search is presented for a singly produced excited bottom quark (b*) decaying to a top quark and a W boson in the all-hadronic, lepton+jets, and dilepton final states in proton-proton collisions at root s = 8 TeV recorded by the CMS experiment at the CERN LHC. Data corresponding to an integrated luminosity of 19.7 fb(-1) are used. No significant excess of events is observed with respect to standard model expectations. We set limits at 95% confidence on the product of the b* quark production cross section and its branching fraction to tW. The cross section limits are interpreted for scenarios including left-handed, right-handed, and vector-like couplings of the b* quark and are presented in the two-dimensional coupling plane based on the production and decay coupling constants. The masses of the left-handed, right-handed, and vector-like b* quark states are excluded at 95% confidence below 1390, 1430, and 1530 GeV, respectively, for benchmark couplings. This analysis gives the most stringent limits on the mass of the b* quark to date.