journal
MENU ▼
Read by QxMD icon Read
search

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

journal
https://www.readbyqxmd.com/read/29343649/topological-transformations-of-hopf-solitons-in-chiral-ferromagnets-and-liquid-crystals
#1
Jung-Shen B Tai, Paul J Ackerman, Ivan I Smalyukh
Liquid crystals are widely known for their facile responses to external fields, which forms a basis of the modern information display technology. However, switching of molecular alignment field configurations typically involves topologically trivial structures, although singular line and point defects often appear as short-lived transient states. Here, we demonstrate electric and magnetic switching of nonsingular solitonic structures in chiral nematic and ferromagnetic liquid crystals. These topological soliton structures are characterized by Hopf indices, integers corresponding to the numbers of times that closed-loop-like spatial regions (dubbed "preimages") of two different single orientations of rod-like molecules or magnetization are linked with each other...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343648/par1-agonists-stimulate-apc-like-endothelial-cytoprotection-and-confer-resistance-to-thromboinflammatory-injury
#2
Karen De Ceunynck, Christian G Peters, Abhishek Jain, Sarah J Higgins, Omozuanvbo Aisiku, Jennifer L Fitch-Tewfik, Sharjeel A Chaudhry, Chris Dockendorff, Samir M Parikh, Donald E Ingber, Robert Flaumenhaft
Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated protein C (APC) is protective in several animal models of disease, and APC has been used clinically in severe sepsis and wound healing. Clinical use of APC, however, is limited by its immunogenicity and its anticoagulant activity. We show that a class of small molecules termed "parmodulins" that act at the cytosolic face of PAR1 stimulates APC-like cytoprotective signaling in endothelium. Parmodulins block thrombin generation in response to inflammatory mediators and inhibit platelet accumulation on endothelium cultured under flow...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343647/on-the-folding-of-a-structurally-complex-protein-to-its-metastable-active-state
#3
V V Hemanth Giri Rao, Shachi Gosavi
For successful protease inhibition, the reactive center loop (RCL) of the two-domain serine protease inhibitor, α1-antitrypsin (α1-AT), needs to remain exposed in a metastable active conformation. The α1-AT RCL is sequestered in a β-sheet in the stable latent conformation. Thus, to be functional, α1-AT must always fold to a metastable conformation while avoiding folding to a stable conformation. We explore the structural basis of this choice using folding simulations of coarse-grained structure-based models of the two α1-AT conformations...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343646/role-of-boundary-conditions-in-determining-cell-alignment-in-response-to-stretch
#4
Kellen Chen, Andrea Vigliotti, Mattia Bacca, Robert M McMeeking, Vikram S Deshpande, Jeffrey W Holmes
The ability of cells to orient in response to mechanical stimuli is essential to embryonic development, cell migration, mechanotransduction, and other critical physiologic functions in a range of organs. Endothelial cells, fibroblasts, mesenchymal stem cells, and osteoblasts all orient perpendicular to an applied cyclic stretch when plated on stretchable elastic substrates, suggesting a common underlying mechanism. However, many of these same cells orient parallel to stretch in vivo and in 3D culture, and a compelling explanation for the different orientation responses in 2D and 3D has remained elusive...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343645/crystal-structure-of-the-mammalian-lipopolysaccharide-detoxifier
#5
Alexei Gorelik, Katalin Illes, Bhushan Nagar
LPS is a potent bacterial endotoxin that triggers the innate immune system. Proper recognition of LPS by pattern-recognition receptors requires a full complement of typically six acyl chains in the lipid portion. Acyloxyacyl hydrolase (AOAH) is a host enzyme that removes secondary (acyloxyacyl-linked) fatty acids from LPS, rendering it immunologically inert. This activity is critical for recovery from immune tolerance that follows Gram-negative infection. To understand the molecular mechanism of AOAH function, we determined its crystal structure and its complex with LPS...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343644/identification-of-genes-required-for-mycobacterium-abscessus-growth-in-vivo-with-a-prominent-role-of-the-esx-4-locus
#6
Laura Laencina, Violaine Dubois, Vincent Le Moigne, Albertus Viljoen, Laleh Majlessi, Justin Pritchard, Audrey Bernut, Laura Piel, Anne-Laure Roux, Jean-Louis Gaillard, Bérengère Lombard, Damarys Loew, Eric J Rubin, Roland Brosch, Laurent Kremer, Jean-Louis Herrmann, Fabienne Girard-Misguich
Mycobacterium abscessus, a rapidly growing mycobacterium (RGM) and an opportunistic human pathogen, is responsible for a wide spectrum of clinical manifestations ranging from pulmonary to skin and soft tissue infections. This intracellular organism can resist the bactericidal defense mechanisms of amoebae and macrophages, an ability that has not been observed in other RGM. M. abscessus can up-regulate several virulence factors during transient infection of amoebae, thereby becoming more virulent in subsequent respiratory infections in mice...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343643/pyridoxal-5-phosphate-as-an-oxygenase-cofactor-discovery-of-a-carboxamide-forming-%C3%AE-amino-acid-monooxygenase-decarboxylase
#7
Ying Huang, Xiaodong Liu, Zheng Cui, Daniel Wiegmann, Giuliana Niro, Christian Ducho, Yuan Song, Zhaoyong Yang, Steven G Van Lanen
Capuramycins are antimycobacterial antibiotics that consist of a modified nucleoside named uridine-5'-carboxamide (CarU). Previous biochemical studies have revealed that CarU is derived from UMP, which is first converted to uridine-5'-aldehyde in a reaction catalyzed by the dioxygenase CapA and subsequently to 5'-C-glycyluridine (GlyU), an unusual β-hydroxy-α-amino acid, in a reaction catalyzed by the pyridoxal-5'-phosphate (PLP)-dependent transaldolase CapH. The remaining steps that are necessary to furnish CarU include decarboxylation, O atom insertion, and oxidation...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343642/mechanogenetics-for-the-remote-and-noninvasive-control-of-cancer-immunotherapy
#8
Yijia Pan, Sangpil Yoon, Jie Sun, Ziliang Huang, Changyang Lee, Molly Allen, Yiqian Wu, Ya-Ju Chang, Michel Sadelain, K Kirk Shung, Shu Chien, Yingxiao Wang
While cell-based immunotherapy, especially chimeric antigen receptor (CAR)-expressing T cells, is becoming a paradigm-shifting therapeutic approach for cancer treatment, there is a lack of general methods to remotely and noninvasively regulate genetics in live mammalian cells and animals for cancer immunotherapy within confined local tissue space. To address this limitation, we have identified a mechanically sensitive Piezo1 ion channel (mechanosensor) that is activatable by ultrasound stimulation and integrated it with engineered genetic circuits (genetic transducer) in live HEK293T cells to convert the ultrasound-activated Piezo1 into transcriptional activities...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343641/degradation-of-fbxo31-by-apc-c-is-regulated-by-akt-and-atm-mediated-phosphorylation
#9
Srinadh Choppara, Sunil K Malonia, Ganga Sankaran, Michael R Green, Manas Kumar Santra
The F-box protein FBXO31 is a tumor suppressor that is encoded in 16q24.3, for which there is loss of heterozygosity in various solid tumors. FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2. FBXO31 levels are normally low but increase substantially following genotoxic stress through a mechanism that remains to be determined...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343640/single-cell-transcriptomics-of-the-developing-lateral-geniculate-nucleus-reveals-insights-into-circuit-assembly-and-refinement
#10
Brian T Kalish, Lucas Cheadle, Sinisa Hrvatin, M Aurel Nagy, Samuel Rivera, Megan Crow, Jesse Gillis, Rory Kirchner, Michael E Greenberg
Coordinated changes in gene expression underlie the early patterning and cell-type specification of the central nervous system. However, much less is known about how such changes contribute to later stages of circuit assembly and refinement. In this study, we employ single-cell RNA sequencing to develop a detailed, whole-transcriptome resource of gene expression across four time points in the developing dorsal lateral geniculate nucleus (LGN), a visual structure in the brain that undergoes a well-characterized program of postnatal circuit development...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339525/pulsating-dissolution-of-crystalline-matter
#11
Cornelius Fischer, Andreas Luttge
Fluid-solid reactions result in material flux from or to the solid surface. The prediction of the flux, its variations, and changes with time are of interest to a wide array of disciplines, ranging from the material and earth sciences to pharmaceutical sciences. Reaction rate maps that are derived from sequences of topography maps illustrate the spatial distribution of reaction rates across the crystal surface. Here, we present highly spatially resolved rate maps that reveal the existence of rhythmic pulses of the material flux from the crystal surface...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339524/communication-in-context-interpreting-promises-in-an-experiment-on-competition-and-trust
#12
Alessandra Casella, Navin Kartik, Luis Sanchez, Sébastien Turban
How much do people lie, and how much do people trust communication when lying is possible? An important step toward answering these questions is understanding how communication is interpreted. This paper establishes in a canonical experiment that competition can alter the shared communication code: the commonly understood meaning of messages. We study a sender-receiver game in which the sender dictates how to share $10 with the receiver, if the receiver participates. The receiver has an outside option and decides whether to participate after receiving a nonbinding offer from the sender...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339523/dna-synthesis-from-diphosphate-substrates-by-dna-polymerases
#13
Cassandra R Burke, Andrej Lupták
The activity of DNA polymerase underlies numerous biotechnologies, cell division, and therapeutics, yet the enzyme remains incompletely understood. We demonstrate that both thermostable and mesophilic DNA polymerases readily utilize deoxyribonucleoside diphosphates (dNDPs) for DNA synthesis and inorganic phosphate for the reverse reaction, that is, phosphorolysis of DNA. For Taq DNA polymerase, the KMs of the dNDP and phosphate substrates are ∼20 and 200 times higher than for dNTP and pyrophosphate, respectively...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339522/effect-of-beta-agonists-on-lam-progression-and-treatment
#14
Kang Le, Wendy K Steagall, Mario Stylianou, Gustavo Pacheco-Rodriguez, Thomas N Darling, Martha Vaughan, Joel Moss
Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also be treated with bronchodilators for asthma-like symptoms due to LAM...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339521/immunogenetic-novelty-confers-a-selective-advantage-in-host-pathogen-coevolution
#15
Karl P Phillips, Joanne Cable, Ryan S Mohammed, Magdalena Herdegen-Radwan, Jarosław Raubic, Karolina J Przesmycka, Cock van Oosterhout, Jacek Radwan
The major histocompatibility complex (MHC) is crucial to the adaptive immune response of vertebrates and is among the most polymorphic gene families known. Its high diversity is usually attributed to selection imposed by fast-evolving pathogens. Pathogens are thought to evolve to escape recognition by common immune alleles, and, hence, novel MHC alleles, introduced through mutation, recombination, or gene flow, are predicted to give hosts superior resistance. Although this theoretical prediction underpins host-pathogen "Red Queen" coevolution, it has not been demonstrated in the context of natural MHC diversity...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339520/targeted-knockout-of-a-chemokine-like-gene-increases-anxiety-and-fear-responses
#16
Jung-Hwa Choi, Yun-Mi Jeong, Sujin Kim, Boyoung Lee, Krishan Ariyasiri, Hyun-Taek Kim, Seung-Hyun Jung, Kyu-Seok Hwang, Tae-Ik Choi, Chul O Park, Won-Ki Huh, Matthias Carl, Jill A Rosenfeld, Salmo Raskin, Alan Ma, Jozef Gecz, Hyung-Goo Kim, Jin-Soo Kim, Ho-Chul Shin, Doo-Sang Park, Robert Gerlai, Bradley B Jamieson, Joon S Kim, Karl J Iremonger, Sang H Lee, Hee-Sup Shin, Cheol-Hee Kim
Emotional responses, such as fear and anxiety, are fundamentally important behavioral phenomena with strong fitness components in most animal species. Anxiety-related disorders continue to represent a major unmet medical need in our society, mostly because we still do not fully understand the mechanisms of these diseases. Animal models may speed up discovery of these mechanisms. The zebrafish is a highly promising model organism in this field. Here, we report the identification of a chemokine-like gene family, samdori (sam), and present functional characterization of one of its members, sam2 We show exclusive mRNA expression of sam2 in the CNS, predominantly in the dorsal habenula, telencephalon, and hypothalamus...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339519/evidence-for-convergent-evolution-of-sine-directed-staufen-mediated-mrna-decay
#17
Bronwyn A Lucas, Eitan Lavi, Lily Shiue, Hana Cho, Sol Katzman, Keita Miyoshi, Mikiko C Siomi, Liran Carmel, Manuel Ares, Lynne E Maquat
Primate-specific Alu short interspersed elements (SINEs) as well as rodent-specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when present in mRNA 3'-untranslated regions (3'-UTRs). The transposable nature of SINEs, their presence in long noncoding RNAs, their interactions with Staufen, and their rapid divergence in different evolutionary lineages suggest they could have generated substantial modification of posttranscriptional gene-control networks during mammalian evolution. Some of the variation in SMD regulation produced by SINE insertion might have had a similar regulatory effect in separate mammalian lineages, leading to parallel evolution of the Staufen network by independent expansion of lineage-specific SINEs...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339518/iterative-optimization-yields-mcl-1-targeting-stapled-peptides-with-selective-cytotoxicity-to-mcl-1-dependent-cancer-cells
#18
Raheleh Rezaei Araghi, Gregory H Bird, Jeremy A Ryan, Justin M Jenson, Marina Godes, Jonathan R Pritz, Robert A Grant, Anthony Letai, Loren D Walensky, Amy E Keating
Bcl-2 family proteins regulate apoptosis, and aberrant interactions of overexpressed antiapoptotic family members such as Mcl-1 promote cell transformation, cancer survival, and resistance to chemotherapy. Discovering potent and selective Mcl-1 inhibitors that can relieve apoptotic blockades is thus a high priority for cancer research. An attractive strategy for disabling Mcl-1 involves using designer peptides to competitively engage its binding groove, mimicking the structural mechanism of action of native sensitizer BH3-only proteins...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339517/infected-erythrocytes-expressing-dc13-pfemp1-differ-from-recombinant-proteins-in-epcr-binding-function
#19
Yvonne Azasi, Gabriella Lindergard, Ashfaq Ghumra, Jianbing Mu, Louis H Miller, J Alexandra Rowe
Recent advances have identified a new paradigm for cerebral malaria pathogenesis in which endothelial protein C receptor (EPCR) is a major host receptor for sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the brain and other vital organs. The parasite adhesins that bind EPCR are members of the IE variant surface antigen family Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) containing specific adhesion domains called domain cassette (DC) 8 and DC13. The binding interaction site between PfEMP1 and EPCR has been mapped by biophysical and crystallography studies using recombinant proteins...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339516/human-airway-branch-variation-and-chronic-obstructive-pulmonary-disease
#20
Benjamin M Smith, Hussein Traboulsi, John H M Austin, Ani Manichaikul, Eric A Hoffman, Eugene R Bleecker, Wellington V Cardoso, Christopher Cooper, David J Couper, Stephen M Dashnaw, Jia Guo, MeiLan K Han, Nadia N Hansel, Emlyn W Hughes, David R Jacobs, Richard E Kanner, Joel D Kaufman, Eric Kleerup, Ching-Long Lin, Kiang Liu, Christian M Lo Cascio, Fernando J Martinez, Jennifer N Nguyen, Martin R Prince, Stephen Rennard, Stephen S Rich, Leora Simon, Yanping Sun, Karol E Watson, Prescott G Woodruff, Carolyn J Baglole, R Graham Barr
Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts (n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
journal
journal
20328
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"