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Proceedings of the National Academy of Sciences of the United States of America

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https://www.readbyqxmd.com/read/30413626/polygenic-adaptation-and-convergent-evolution-on-growth-and-cardiac-genetic-pathways-in-african-and-asian-rainforest-hunter-gatherers
#1
Christina M Bergey, Marie Lopez, Genelle F Harrison, Etienne Patin, Jacob A Cohen, Lluís Quintana-Murci, Luis B Barreiro, George H Perry
Different human populations facing similar environmental challenges have sometimes evolved convergent biological adaptations, for example, hypoxia resistance at high altitudes and depigmented skin in northern latitudes on separate continents. The "pygmy" phenotype (small adult body size), characteristic of hunter-gatherer populations inhabiting both African and Asian tropical rainforests, is often highlighted as another case of convergent adaptation in humans. However, the degree to which phenotypic convergence in this polygenic trait is due to convergent versus population-specific genetic changes is unknown...
November 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30413625/remote-optimization-of-an-ultracold-atoms-experiment-by-experts-and-citizen-scientists
#2
Robert Heck, Oana Vuculescu, Jens Jakob Sørensen, Jonathan Zoller, Morten G Andreasen, Mark G Bason, Poul Ejlertsen, Ottó Elíasson, Pinja Haikka, Jens S Laustsen, Lærke L Nielsen, Andrew Mao, Romain Müller, Mario Napolitano, Mads K Pedersen, Aske R Thorsen, Carsten Bergenholtz, Tommaso Calarco, Simone Montangero, Jacob F Sherson
We introduce a remote interface to control and optimize the experimental production of Bose-Einstein condensates (BECs) and find improved solutions using two distinct implementations. First, a team of theoreticians used a remote version of their dressed chopped random basis optimization algorithm (RedCRAB), and second, a gamified interface allowed 600 citizen scientists from around the world to participate in real-time optimization. Quantitative studies of player search behavior demonstrated that they collectively engage in a combination of local and global searches...
November 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30413624/multiple-prebiotic-metals-mediate-translation
#3
Marcus S Bray, Timothy K Lenz, Jay William Haynes, Jessica C Bowman, Anton S Petrov, Amit R Reddi, Nicholas V Hud, Loren Dean Williams, Jennifer B Glass
Today, Mg2+ is an essential cofactor with diverse structural and functional roles in life's oldest macromolecular machine, the translation system. We tested whether ancient Earth conditions (low O2 , high Fe2+ , and high Mn2+ ) can revert the ribosome to a functional ancestral state. First, SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) was used to compare the effect of Mg2+ , Fe2+ , and Mn2+ on the tertiary structure of rRNA. Then, we used in vitro translation reactions to test whether Fe2+ or Mn2+ could mediate protein production, and quantified ribosomal metal content...
November 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30413623/chromatin-modifiers-mdm2-and-rnf2-prevent-rna-dna-hybrids-that-impair-dna-replication
#4
Ina Klusmann, Kai Wohlberedt, Anna Magerhans, Federico Teloni, Jan O Korbel, Matthias Altmeyer, Matthias Dobbelstein
The p53-Mdm2 system is key to tumor suppression. We have recently reported that p53 as well as Mdm2 are capable of supporting DNA replication fork progression. On the other hand, we found that Mdm2 is a modifier of chromatin, modulating polycomb repressor complex (PRC)-driven histone modifications. Here we show that, similar to Mdm2 knockdown, the depletion of PRC members impairs DNA synthesis, as determined in fiber assays. In particular, the ubiquitin ligase and PRC1 component RNF2/Ring1B is required to support DNA replication, similar to Mdm2...
November 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30413622/flavonols-control-pollen-tube-growth-and-integrity-by-regulating-ros-homeostasis-during-high-temperature-stress
#5
Joëlle K Muhlemann, Trenton L B Younts, Gloria K Muday
Plant reproduction requires long-distance growth of a pollen tube to fertilize the female gametophyte. Prior reports suggested that mutations altering synthesis of flavonoids, plant specialized metabolites that include flavonols and anthocyanins, impair pollen development in several species, but the mechanism by which flavonols enhanced fertility was not defined. Here, we used genetic approaches to demonstrate that flavonols enhanced pollen development by reducing the abundance of reactive oxygen species (ROS)...
November 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30413621/folding-pathway-of-an-ig-domain-is-conserved-on-and-off-the-ribosome
#6
Pengfei Tian, Annette Steward, Renuka Kudva, Ting Su, Patrick J Shilling, Adrian A Nickson, Jeffrey J Hollins, Roland Beckmann, Gunnar von Heijne, Jane Clarke, Robert B Best
Proteins that fold cotranslationally may do so in a restricted configurational space, due to the volume occupied by the ribosome. How does this environment, coupled with the close proximity of the ribosome, affect the folding pathway of a protein? Previous studies have shown that the cotranslational folding process for many proteins, including small, single domains, is directly affected by the ribosome. Here, we investigate the cotranslational folding of an all-β Ig domain, titin I27. Using an arrest peptide-based assay and structural studies by cryo-EM, we show that I27 folds in the mouth of the ribosome exit tunnel...
November 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30413620/klotho-controls-the-brain-immune-system-interface-in-the-choroid-plexus
#7
Lei Zhu, Liana R Stein, Daniel Kim, Kaitlyn Ho, Gui-Qiu Yu, Lihong Zhan, Tobias E Larsson, Lennart Mucke
Located within the brain's ventricles, the choroid plexus produces cerebrospinal fluid and forms an important barrier between the central nervous system and the blood. For unknown reasons, the choroid plexus produces high levels of the protein klotho. Here, we show that these levels naturally decline with aging. Depleting klotho selectively from the choroid plexus via targeted viral vector-induced knockout in Klotho flox/flox mice increased the expression of multiple proinflammatory factors and triggered macrophage infiltration of this structure in young mice, simulating changes in unmanipulated old mice...
November 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30413619/simplicial-closure-and-higher-order-link-prediction
#8
Austin R Benson, Rediet Abebe, Michael T Schaub, Ali Jadbabaie, Jon Kleinberg
Networks provide a powerful formalism for modeling complex systems by using a model of pairwise interactions. But much of the structure within these systems involves interactions that take place among more than two nodes at once-for example, communication within a group rather than person to person, collaboration among a team rather than a pair of coauthors, or biological interaction between a set of molecules rather than just two. Such higher-order interactions are ubiquitous, but their empirical study has received limited attention, and little is known about possible organizational principles of such structures...
November 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30413618/quantitative-constraints-on-autoxidation-and-dimer-formation-from-direct-probing-of-monoterpene-derived-peroxy-radical-chemistry
#9
Yue Zhao, Joel A Thornton, Havala O T Pye
Organic peroxy radicals (RO2 ) are key intermediates in the atmospheric degradation of organic matter and fuel combustion, but to date, few direct studies of specific RO2 in complex reaction systems exist, leading to large gaps in our understanding of their fate. We show, using direct, speciated measurements of a suite of RO2 and gas-phase dimers from O3 -initiated oxidation of α-pinene, that ∼150 gaseous dimers (C16-20 H24-34 O4-13 ) are primarily formed through RO2 cross-reactions, with a typical rate constant of 0...
November 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30413617/genome-wide-rna-structurome-reprogramming-by-acute-heat-shock-globally-regulates-mrna-abundance
#10
Zhao Su, Yin Tang, Laura E Ritchey, David C Tack, Mengmeng Zhu, Philip C Bevilacqua, Sarah M Assmann
The heat shock response is crucial for organism survival in natural environments. RNA structure is known to influence numerous processes related to gene expression, but there have been few studies on the global RNA structurome as it prevails in vivo. Moreover, how heat shock rapidly affects RNA structure genome-wide in living systems remains unknown. We report here in vivo heat-regulated RNA structuromes. We applied Structure-seq chemical [dimethyl sulfate (DMS)] structure probing to rice ( Oryza sativa L.) seedlings with and without 10 min of 42 °C heat shock and obtained structural data on >14,000 mRNAs...
November 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30413616/golgi-localized-lot-regulates-trans-golgi-network-biogenesis-and-pollen-tube-growth
#11
Peng-Fei Jia, Yong Xue, Hong-Ju Li, Wei-Cai Yang
The trans -Golgi network (TGN) is an essential tubular-vesicular organelle derived from the Golgi and functions as an independent sorting and trafficking hub within the cell. However, the molecular regulation of TGN biogenesis remains enigmatic. Here we identified an Arabidopsis mutant loss of TGN ( lot ) that is defective in TGN formation and sterile due to impaired pollen tube growth in the style. The mutation leads to overstacking of the Golgi cisternae and significant reduction in the number of TGNs and vesicles surrounding the Golgi in pollen, which is corroborated by the dispersed cytosolic distribution of TGN-localized proteins...
November 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30413615/themis-associated-phosphatase-activity-controls-signaling-in-t-cell-development
#12
Monika Mehta, Joanna Brzostek, Elijah W Chen, Desmond W H Tung, Shuting Chen, Shvetha Sankaran, Jiawei Yap, Vasily Rybakin, Nicholas R J Gascoigne
Thymocyte-expressed molecule involved in selection (Themis) has been shown to be important for T cell selection by setting the threshold for positive versus negative selection. Themis interacts with the protein tyrosine phosphatase (PTP) Src-homology domain containing phosphatase-1 (Shp1), a negative regulator of the T cell receptor (TCR) signaling cascade. However, how Themis regulates Shp1 is still not clear. Here, using a very sensitive phosphatase assay on ex vivo thymocytes, we have found that Themis enhances Shp1 phosphatase activity by increasing its phosphorylation...
November 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30409803/a-small-single-domain-protein-folds-through-the-same-pathway-on-and-off-the-ribosome
#13
Emily J Guinn, Pengfei Tian, Mia Shin, Robert B Best, Susan Marqusee
In vivo, proteins fold and function in a complex environment subject to many stresses that can modulate a protein's energy landscape. One aspect of the environment pertinent to protein folding is the ribosome, since proteins have the opportunity to fold while still bound to the ribosome during translation. We use a combination of force and chemical denaturant (chemomechanical unfolding), as well as point mutations, to characterize the folding mechanism of the src SH3 domain both as a stalled ribosome nascent chain and free in solution...
November 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30409802/comparative-genomics-reveals-the-molecular-determinants-of-rapid-growth-of-the-cyanobacterium-synechococcus-elongatus-utex-2973
#14
Justin Ungerer, Kristen E Wendt, John I Hendry, Costas D Maranas, Himadri B Pakrasi
Cyanobacteria are emerging as attractive organisms for sustainable bioproduction. We previously described Synechococcus elongatus UTEX 2973 as the fastest growing cyanobacterium known. Synechococcus 2973 exhibits high light tolerance and an increased photosynthetic rate and produces biomass at three times the rate of its close relative, the model strain Synechococcus elongatus 7942. The two strains differ at 55 genetic loci, and s ome of these loci must contain the genetic determinants of rapid photoautotrophic growth and improved photosynthetic rate...
November 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30409801/cell-size-control-driven-by-the-circadian-clock-and-environment-in-cyanobacteria
#15
Bruno M C Martins, Amy K Tooke, Philipp Thomas, James C W Locke
How cells maintain their size has been extensively studied under constant conditions. In the wild, however, cells rarely experience constant environments. Here, we examine how the 24-h circadian clock and environmental cycles modulate cell size control and division timings in the cyanobacterium Synechococcus elongatus using single-cell time-lapse microscopy. Under constant light, wild-type cells follow an apparent sizer-like principle. Closer inspection reveals that the clock generates two subpopulations, with cells born in the subjective day following different division rules from cells born in subjective night...
November 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30409800/emergence-of-phytoplankton-patchiness-at-small-scales-in-mild-turbulence
#16
Rebekka E Breier, Cristian C Lalescu, Devin Waas, Michael Wilczek, Marco G Mazza
Phytoplankton often encounter turbulence in their habitat. As most toxic phytoplankton species are motile, resolving the interplay of motility and turbulence has fundamental repercussions on our understanding of their own ecology and of the entire ecosystems they inhabit. The spatial distribution of motile phytoplankton cells exhibits patchiness at distances of decimeter to millimeter scales for numerous species with different motility strategies. The explanation of this general phenomenon remains challenging...
November 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30404918/noxa-genetic-amplification-or-pharmacologic-induction-primes-lymphoma-cells-to-bcl2-inhibitor-induced-cell-death
#17
Yuxuan Liu, Patrizia Mondello, Tatiana Erazo, Neeta Bala Tannan, Zahra Asgari, Elisa de Stanchina, Gouri Nanjangud, Venkatraman E Seshan, Shenqiu Wang, Hans-Guido Wendel, Anas Younes
Although diffuse large B cell lymphoma (DLBCL) cells widely express the BCL2 protein, they rarely respond to treatment with BCL2-selective inhibitors. Here we show that DLBCL cells harboring PMAIP1/NOXA gene amplification were highly sensitive to BCL2 small-molecule inhibitors. In these cells, BCL2 inhibition induced cell death by activating caspase 9, which was further amplified by caspase-dependent cleavage and depletion of MCL1. In DLBCL cells lacking NOXA amplification, BCL2 inhibition was associated with an increase in MCL1 protein abundance in a BIM-dependent manner, causing a decreased antilymphoma efficacy...
November 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30404917/-drosophila-intestinal-stem-and-progenitor-cells-are-major-sources-and-regulators-of-homeostatic-niche-signals
#18
David P Doupé, Owen J Marshall, Hannah Dayton, Andrea H Brand, Norbert Perrimon
Epithelial homeostasis requires the precise balance of epithelial stem/progenitor proliferation and differentiation. While many signaling pathways that regulate epithelial stem cells have been identified, it is probable that other regulators remain unidentified. Here, we use gene-expression profiling by targeted DamID to identify the stem/progenitor-specific transcription and signaling factors in the Drosophila midgut. Many signaling pathway components, including ligands of most major pathways, exhibit stem/progenitor-specific expression and have regulatory regions bound by both intrinsic and extrinsic transcription factors...
November 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30404916/coupled-molecular-dynamics-mediate-long-and-short-range-epistasis-between-mutations-that-affect-stability-and-aggregation-kinetics
#19
Haoran Yu, Paul A Dalby
Multiple mutations are typically required to significantly improve protein stability or aggregation kinetics. However, when several substitutions are made in a single protein, the mutations can potentially interact in a nonadditive manner, resulting in epistatic effects, which can hamper protein-engineering strategies to improve thermostability or aggregation kinetics. Here, we have examined the role of protein dynamics in mediating epistasis between pairs of mutations. With Escherichia coli transketolase (TK) as a model, we explored the epistatic interactions between two single variants H192P and A282P, and also between the double-mutant H192P/A282P and two single variants, I365L or G506A...
November 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30404915/evolution-of-weak-cooperative-interactions-for-biological-specificity
#20
Ang Gao, Krishna Shrinivas, Paul Lepeudry, Hiroshi I Suzuki, Phillip A Sharp, Arup K Chakraborty
A hallmark of biological systems is that particular functions and outcomes are realized in specific contexts, such as when particular signals are received. One mechanism for mediating specificity is described by Fisher's "lock and key" metaphor, exemplified by enzymes that bind selectively to a particular substrate via specific finely tuned interactions. Another mechanism, more prevalent in multicellular organisms, relies on multivalent weak cooperative interactions. Its importance has recently been illustrated by the recognition that liquid-liquid phase transitions underlie the formation of membraneless condensates that perform specific cellular functions...
November 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
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