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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/28228531/both-rare-and-common-erap1-allotypes-have-distinct-functionality-defined-by-polymorphic-context-and-are-important-in-as-association
#1
LETTER
Emma Reeves, Tim Elliott, Christopher J Edwards, Edward James
No abstract text is available yet for this article.
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228530/optical-detection-of-nanometric-thermal-fluctuations-to-measure-the-stiffness-of-rigid-superparamagnetic-microrods
#2
Fabien Gerbal, Yuan Wang
The rigidity of numerous biological filaments and crafted microrods has been conveniently deduced from the analysis of their thermal fluctuations. However, the difficulty of measuring nanometric displacements with an optical microscope has so far limited such studies to sufficiently flexible rods, of which the persistence length ([Formula: see text]) rarely exceeds 1 m at room temperature. Here, we demonstrate the possibility to probe 10-fold stiffer rods by a combination of superresolutive optical methods and a statistical analysis of the data based on a recent theoretical model that predicts the amplitude of the fluctuations at any location of the rod [Benetatos P, Frey E (2003) Phys Rev E Stat Nonlin Soft Matter Phys 67(5):051108]...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228529/recapitulation-of-physiological-spatiotemporal-signals-promotes-in-vitro-formation-of-phenotypically-stable-human-articular-cartilage
#3
Johnathan J Ng, Yiyong Wei, Bin Zhou, Jonathan Bernhard, Samuel Robinson, Aonnicha Burapachaisri, X Edward Guo, Gordana Vunjak-Novakovic
Standard isotropic culture fails to recapitulate the spatiotemporal gradients present during native development. Cartilage grown from human mesenchymal stem cells (hMSCs) is poorly organized and unstable in vivo. We report that human cartilage with physiologic organization and in vivo stability can be grown in vitro from self-assembling hMSCs by implementing spatiotemporal regulation during induction. Self-assembling hMSCs formed cartilage discs in Transwell inserts following isotropic chondrogenic induction with transforming growth factor β to set up a dual-compartment culture...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228528/clinical-genetic-and-structural-basis-of-congenital-adrenal-hyperplasia-due-to-11%C3%AE-hydroxylase-deficiency
#4
Ahmed Khattab, Shozeb Haider, Ameet Kumar, Samarth Dhawan, Dauood Alam, Raquel Romero, James Burns, Di Li, Jessica Estatico, Simran Rahi, Saleel Fatima, Ali Alzahrani, Mona Hafez, Noha Musa, Maryam Razzghy Azar, Najoua Khaloul, Moez Gribaa, Ali Saad, Ilhem Ben Charfeddine, Berenice Bilharinho de Mendonça, Alicia Belgorosky, Katja Dumic, Miroslav Dumic, Javier Aisenberg, Nurgun Kandemir, Ayfer Alikasifoglu, Alev Ozon, Nazli Gonc, Tina Cheng, Ursula Kuhnle-Krahl, Marco Cappa, Paul-Martin Holterhus, Munier A Nour, Daniele Pacaud, Assaf Holtzman, Sun Li, Mone Zaidi, Tony Yuen, Maria I New
Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228527/activation-mechanism-of-the-g-protein-coupled-sweet-receptor-heterodimer-with-sweeteners-and-allosteric-agonists
#5
Soo-Kyung Kim, Yalu Chen, Ravinder Abrol, William A Goddard, Brian Guthrie
The sweet taste in humans is mediated by the TAS1R2/TAS1R3 G protein-coupled receptor (GPCR), which belongs to the class C family that also includes the metabotropic glutamate and γ-aminobutyric acid receptors. We report here the predicted 3D structure of the full-length TAS1R2/TAS1R3 heterodimer, including the Venus Flytrap Domains (VFDs) [in the closed-open (co) active conformation], the cysteine-rich domains (CRDs), and the transmembrane domains (TMDs) at the TM56/TM56 interface. We observe that binding of agonists to VFD2 of TAS1R2 leads to major conformational changes to form a TM6/TM6 interface between TMDs of TAS1R2 and TAS1R3, which is consistent with the activation process observed biophysically on the metabotropic glutamate receptor 2 homodimer...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228526/trimethylamine-n-oxide-stabilizes-proteins-via-a-distinct-mechanism-compared-with-betaine-and-glycine
#6
Yi-Ting Liao, Anthony C Manson, Michael R DeLyser, William G Noid, Paul S Cremer
We report experimental and computational studies investigating the effects of three osmolytes, trimethylamine N-oxide (TMAO), betaine, and glycine, on the hydrophobic collapse of an elastin-like polypeptide (ELP). All three osmolytes stabilize collapsed conformations of the ELP and reduce the lower critical solution temperature (LSCT) linearly with osmolyte concentration. As expected from conventional preferential solvation arguments, betaine and glycine both increase the surface tension at the air-water interface...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228525/chirality-induced-spin-polarization-places-symmetry-constraints-on-biomolecular-interactions
#7
Anup Kumar, Eyal Capua, Manoj K Kesharwani, Jan M L Martin, Einat Sitbon, David H Waldeck, Ron Naaman
Noncovalent interactions between molecules are key for many biological processes. Necessarily, when molecules interact, the electronic charge in each of them is redistributed. Here, we show experimentally that, in chiral molecules, charge redistribution is accompanied by spin polarization. We describe how this spin polarization adds an enantioselective term to the forces, so that homochiral interaction energies differ from heterochiral ones. The spin polarization was measured by using a modified Hall effect device...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228524/structural-insights-into-the-activation-mechanism-of-dynamin-like-ehd-atpases
#8
Arthur Alves Melo, Balachandra G Hegde, Claudio Shah, Elin Larsson, J Mario Isas, Séverine Kunz, Richard Lundmark, Ralf Langen, Oliver Daumke
Eps15 (epidermal growth factor receptor pathway substrate 15)-homology domain containing proteins (EHDs) comprise a family of dynamin-related mechano-chemical ATPases involved in cellular membrane trafficking. Previous studies have revealed the structure of the EHD2 dimer, but the molecular mechanisms of membrane recruitment and assembly have remained obscure. Here, we determined the crystal structure of an amino-terminally truncated EHD4 dimer. Compared with the EHD2 structure, the helical domains are 50° rotated relative to the GTPase domain...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228523/vpx-overcomes-a-samhd1-independent-block-to-hiv-reverse-transcription-that-is-specific-to-resting-cd4-t-cells
#9
Hanna-Mari Baldauf, Lena Stegmann, Sarah-Marie Schwarz, Ina Ambiel, Maud Trotard, Margarethe Martin, Manja Burggraf, Gina M Lenzi, Helena Lejk, Xiaoyu Pan, Oliver I Fregoso, Efrem S Lim, Libin Abraham, Laura A Nguyen, Frank Rutsch, Renate König, Baek Kim, Michael Emerman, Oliver T Fackler, Oliver T Keppler
Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228522/entropy-driven-segregation-of-polymer-grafted-nanoparticles-under-confinement
#10
Ren Zhang, Bongjoon Lee, Christopher M Stafford, Jack F Douglas, Andrey V Dobrynin, Michael R Bockstaller, Alamgir Karim
The modification of nanoparticles with polymer ligands has emerged as a versatile approach to control the interactions and organization of nanoparticles in polymer nanocomposite materials. Besides their technological significance, polymer-grafted nanoparticle (PGNP) dispersions have attracted interest as model systems to understand the role of entropy as a driving force for microstructure formation. For instance, densely and sparsely grafted nanoparticles show distinct dispersion and assembly behaviors within polymer matrices due to the entropy variation associated with conformational changes in brush and matrix chains...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28228521/clustered-brachiopod-hox-genes-are-not-expressed-collinearly-and-are-associated-with-lophotrochozoan-novelties
#11
Sabrina M Schiemann, José M Martín-Durán, Aina Børve, Bruno C Vellutini, Yale J Passamaneck, Andreas Hejnol
Temporal collinearity is often considered the main force preserving Hox gene clusters in animal genomes. Studies that combine genomic and gene expression data are scarce, however, particularly in invertebrates like the Lophotrochozoa. As a result, the temporal collinearity hypothesis is currently built on poorly supported foundations. Here we characterize the complement, cluster, and expression of Hox genes in two brachiopod species, Terebratalia transversa and Novocrania anomalaT. transversa has a split cluster with 10 genes (lab, pb, Hox3, Dfd, Scr, Lox5, Antp, Lox4, Post2, and Post1), whereas N...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223535/giant-ripples-on-comet-67p-churyumov-gerasimenko-sculpted-by-sunset-thermal-wind
#12
Pan Jia, Bruno Andreotti, Philippe Claudin
Explaining the unexpected presence of dune-like patterns at the surface of the comet 67P/Churyumov-Gerasimenko requires conceptual and quantitative advances in the understanding of surface and outgassing processes. We show here that vapor flow emitted by the comet around its perihelion spreads laterally in a surface layer, due to the strong pressure difference between zones illuminated by sunlight and those in shadow. For such thermal winds to be dense enough to transport grains-10 times greater than previous estimates-outgassing must take place through a surface porous granular layer, and that layer must be composed of grains whose roughness lowers cohesion consistently with contact mechanics...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223534/designing-allostery-inspired-response-in-mechanical-networks
#13
Jason W Rocks, Nidhi Pashine, Irmgard Bischofberger, Carl P Goodrich, Andrea J Liu, Sidney R Nagel
Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ∼1% of the bonds...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223533/generalized-myoclonic-epilepsy-with-photosensitivity-in-juvenile-dogs-caused-by-a-defective-diras-family-gtpase-1
#14
Franziska Wielaender, Riika Sarviaho, Fiona James, Marjo K Hytönen, Miguel A Cortez, Gerhard Kluger, Lotta L E Koskinen, Meharji Arumilli, Marion Kornberg, Andrea Bathen-Noethen, Andrea Tipold, Kai Rentmeister, Sofie F M Bhatti, Velia Hülsmeyer, Irene C Boettcher, Carina Tästensen, Thomas Flegel, Elisabeth Dietschi, Tosso Leeb, Kaspar Matiasek, Andrea Fischer, Hannes Lohi
The clinical and electroencephalographic features of a canine generalized myoclonic epilepsy with photosensitivity and onset in young Rhodesian Ridgeback dogs (6 wk to 18 mo) are described. A fully penetrant recessive 4-bp deletion was identified in the DIRAS family GTPase 1 (DIRAS1) gene with an altered expression pattern of DIRAS1 protein in the affected brain. This neuronal DIRAS1 gene with a proposed role in cholinergic transmission provides not only a candidate for human myoclonic epilepsy but also insights into the disease etiology, while establishing a spontaneous model for future intervention studies and functional characterization...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223532/identification-of-productive-and-futile-encounters-in-an-electron-transfer-protein-complex
#15
Witold Andrałojć, Yoshitaka Hiruma, Wei-Min Liu, Enrico Ravera, Masaki Nojiri, Giacomo Parigi, Claudio Luchinat, Marcellus Ubbink
Well-defined, stereospecific states in protein complexes are often in exchange with an ensemble of more dynamic orientations: the encounter states. The structure of the stereospecific complex between cytochrome P450cam and putidaredoxin was solved recently by X-ray diffraction as well as paramagnetic NMR spectroscopy. Other than the stereospecific complex, the NMR data clearly show the presence of additional states in the complex in solution. In these encounter states, populated for a small percentage of the time, putidaredoxin assumes multiple orientations and samples a large part of the surface of cytochrome P450cam...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223531/real-space-renormalization-group-theory-of-disordered-models-of-glasses
#16
Maria Chiara Angelini, Giulio Biroli
We develop a real space renormalization group analysis of disordered models of glasses, in particular of the spin models at the origin of the random first-order transition theory. We find three fixed points, respectively, associated with the liquid state, with the critical behavior, and with the glass state. The latter two are zero-temperature ones; this provides a natural explanation of the growth of effective activation energy scale and the concomitant huge increase of relaxation time approaching the glass transition...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223530/differential-tor-activation-and-cell-proliferation-in-arabidopsis-root-and-shoot-apexes
#17
Xiaojuan Li, Wenguo Cai, Yanlin Liu, Hui Li, Liwen Fu, Zengyu Liu, Lin Xu, Hongtao Liu, Tongda Xu, Yan Xiong
The developmental plasticity of plants relies on the remarkable ability of the meristems to integrate nutrient and energy availability with environmental signals. Meristems in root and shoot apexes share highly similar molecular players but are spatially separated by soil. Whether and how these two meristematic tissues have differential activation requirements for local nutrient, hormone, and environmental cues (e.g., light) remain enigmatic in photosynthetic plants. Here, we report that the activation of root and shoot apexes relies on distinct glucose and light signals...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223529/social-ecological-network-analysis-of-scale-mismatches-in-estuary-watershed-restoration
#18
Jesse S Sayles, Jacopo A Baggio
Resource management boundaries seldom align with environmental systems, which can lead to social and ecological problems. Mapping and analyzing how resource management organizations in different areas collaborate can provide vital information to help overcome such misalignment. Few quantitative approaches exist, however, to analyze social collaborations alongside environmental patterns, especially among local and regional organizations (i.e., in multilevel governance settings). This paper develops and applies such an approach using social-ecological network analysis (SENA), which considers relationships among and between social and ecological units...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223528/inhibition-of-%C3%AE-9%C3%AE-10-nicotinic-acetylcholine-receptors-prevents-chemotherapy-induced-neuropathic-pain
#19
Haylie K Romero, Sean B Christensen, Lorenzo Di Cesare Mannelli, Joanna Gajewiak, Renuka Ramachandra, Keith S Elmslie, Douglas E Vetter, Carla Ghelardini, Shawn P Iadonato, Jose L Mercado, Baldomera M Olivera, J Michael McIntosh
Opioids are first-line drugs for moderate to severe acute pain and cancer pain. However, these medications are associated with severe side effects, and whether they are efficacious in treatment of chronic nonmalignant pain remains controversial. Medications that act through alternative molecular mechanisms are critically needed. Antagonists of α9α10 nicotinic acetylcholine receptors (nAChRs) have been proposed as an important nonopioid mechanism based on studies demonstrating prevention of neuropathology after trauma-induced nerve injury...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223527/ancient-x-chromosomes-reveal-contrasting-sex-bias-in-neolithic-and-bronze-age-eurasian-migrations
#20
Amy Goldberg, Torsten Günther, Noah A Rosenberg, Mattias Jakobsson
Dramatic events in human prehistory, such as the spread of agriculture to Europe from Anatolia and the late Neolithic/Bronze Age migration from the Pontic-Caspian Steppe, can be investigated using patterns of genetic variation among the people who lived in those times. In particular, studies of differing female and male demographic histories on the basis of ancient genomes can provide information about complexities of social structures and cultural interactions in prehistoric populations. We use a mechanistic admixture model to compare the sex-specifically-inherited X chromosome with the autosomes in 20 early Neolithic and 16 late Neolithic/Bronze Age human remains...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
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