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https://www.readbyqxmd.com/read/28432925/structure-of-the-s1-subunit-c-terminal-domain-from-bat-derived-coronavirus-hku5-spike-protein
#1
Xue Han, Jianxun Qi, Hao Song, Qihui Wang, Yanfang Zhang, Ying Wu, Guangwen Lu, Kwok-Yung Yuen, Yi Shi, George F Gao
Accumulating evidence indicates that MERS-CoV originated from bat coronaviruses (BatCoVs). Previously, we demonstrated that both MERS-CoV and BatCoV HKU4 use CD26 as a receptor, but how the BatCoVs evolved to bind CD26 is an intriguing question. Here, we solved the crystal structure of the S1 subunit C-terminal domain of HKU5 (HKU5-CTD), another BatCoV that is phylogenetically related to MERS-CoV but cannot bind to CD26. We observed that the conserved core subdomain and those of other betacoronaviruses (betaCoVs) have a similar topology of the external subdomain, indicating the same ancestor of lineage C betaCoVs...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28432473/vasopressin-and-vasopressin-antagonists-in-heart-failure
#2
Julie K Vishram-Nielsen, Finn Gustafsson
Despite the introduction of multiple new pharmacological agents over the past three decades in the field of heart failure (HF), overall prognosis remains poor. Hyponatremia is prevalent in HF patients and has been suggested as a contributor to poor response to standard therapy. Elevated levels of arginine vasopressin (AVP), a peptide hormone produced in the hypothalamus, play a role in development of hyponatremia, and AVP and its surrogate, copeptin, are related to changes in osmolality, hemodynamics, neuro-hormones as well as in overall outcome in HF patients...
April 22, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28432455/dual-activation-of-toll-like-receptors-7-and-9-impairs-the-efficacy-of-antitumor-vaccines-in-murine-models-of-metastatic-breast-cancer
#3
Mariela A Moreno Ayala, María Florencia Gottardo, María Soledad Gori, Alejandro Javier Nicola Candia, Carla Caruso, Andrea De Laurentiis, Mercedes Imsen, Slobodanka Klein, Elisa Bal de Kier Joffé, Gabriela Salamone, Maria G Castro, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28432363/joint-based-description-of-protein-structure-its-application-to-the-geometric-characterization-of-membrane-proteins
#4
Jayaraman Thangappan, Sangwook Wu, Sun-Gu Lee
A macroscopic description of a protein structure allows an understanding of the protein conformations in a more simplistic manner. Here, a new macroscopic approach that utilizes the joints of the protein secondary structures as a basic descriptor for the protein structure is proposed and applied to study the arrangement of secondary structures in helical membrane proteins. Two types of dihedral angle, Ω and λ, were defined based on the joint points of the transmembrane (TM) helices and loops, and employed to analyze 103 non-homologous membrane proteins with 3 to 14 TM helices...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432346/functionally-interchangeable-cis-acting-rna-elements-in-both-genome-segments-of-a-picorna-like-plant-virus
#5
Jiangbo Guo, Junping Han, Junyan Lin, John Finer, Anne Dorrance, Feng Qu
Cis-acting RNA structures in the genomes of RNA viruses play critical roles in viral infection, yet their importance in the bipartite genomes of the picorna-like, plant-infecting comoviruses has not been carefully investigated. We previously characterized SLC, a stem-loop structure in the 5' untranslated region (UTR) of the bean pod mottle comovirus (BPMV) RNA2, and found it to be essential for RNA2 accumulation in infected cells. Here we report the identification of SL1, a similar cis-acting element in the other BPMV genome segment - RNA1...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432303/closed-loop-deep-brain-stimulation-by-pulsatile-delayed-feedback-with-increased-gap-between-pulse-phases
#6
Oleksandr V Popovych, Borys Lysyansky, Peter A Tass
Computationally it was shown that desynchronizing delayed feedback stimulation methods are effective closed-loop techniques for the control of synchronization in ensembles of interacting oscillators. We here computationally design stimulation signals for electrical stimulation of neuronal tissue that preserve the desynchronizing delayed feedback characteristics and comply with mandatory charge deposit-related safety requirements. For this, the amplitude of the high-frequency (HF) train of biphasic charge-balanced pulses used by the standard HF deep brain stimulation (DBS) is modulated by the smooth feedback signals...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432123/an-amphipathic-%C3%AE-helix-directs-palmitoylation-of-the-large-intracellular-loop-of-the-sodium-calcium-exchanger
#7
Fiona Plain, Samitha Dilini Congreve, Rachel Sue Zhen Yee, Jennifer Kennedy, Jacqueline Howie, Chien-Wen Kuo, Niall Fraser, William Fuller
The electrogenic sodium/calcium exchanger (NCX) mediates bidirectional calcium transport controlled by the transmembrane sodium gradient. NCX inactivation occurs in the absence of phosphatidylinositol 4,5-bisphosphate (PIP2), and is facilitated by palmitoylation of a single cysteine at position 739 within NCX's large intracellular loop. The aim of this investigation was to identify the structural determinants of NCX1 palmitoylation. Full-length NCX1 (FL-NCX1) and a YFP fusion protein of the NCX1 large intracellular loop (YFP-NCX1) were expressed in HEK cells...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432122/dual-regulation-of-stat1-and-stat3-by-the-tumor-suppressor-protein-pml-contributes-to-ifn%C3%AE-mediated-inhibition-of-angiogenesis
#8
Kuo-Sheng Hsu, Xuan Zhao, Xiwen Cheng, Dongyin Guan, Ganapati H Mahabeleshwar, Yu Liu, Ernest Borden, Mukesh K Jain, Hung-Ying Kao
IFNs are effective in inhibiting angiogenesis in preclinical models and in treating several angio-proliferative disorders. However, the detailed mechanisms of IFNα-mediated anti-angiogenesis are not completely understood. Stat1/2/3 and PML are IFNα downstream effectors and are pivotal regulators of angiogenesis. Here, we investigated PML's role in the regulation of Stat1/2/3 activity. In Pml knockout (KO) mice, ablation of Pml largely reduces IFNα angiostatic ability in Matrixgel plug assays. This suggested an essential role for PML in IFNα's anti-angiogenic function...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432120/two-glycosaminoglycan-binding-domains-of-the-mouse-cytomegalovirus-encoded-chemokine-mck-2-are-critical-for-oligomerization-of-the-full-length-protein
#9
Sergio M Pontejo, Philip M Murphy
Chemokines are essential for antimicrobial host defenses and tissue repair. Herpesviruses and poxviruses also encode chemokines, copied from their hosts and repurposed for multiple functions, including immune evasion. The CC chemokine MCK-2 encoded by mouse cytomegalovirus (MCMV) has an atypical structure consisting of a classic chemokine domain N-terminal to a second unique domain, resulting from the splicing of MCMV ORFs m131 and m129. MCK-2 is essential for full MCMV infectivity in macrophages and for persistent infection in the salivary gland...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28431964/microvillus-specific-protein-tyrosine-phosphatase-sap-1-plays-a-role-in-regulating-the-intestinal-paracellular-transport-of-macromolecules
#10
Shingo Mori, Noriyasu Kamei, Yoji Murata, Kozo Takayama, Takashi Matozaki, Mariko Takeda-Morishita
The stomach cancer associated protein tyrosine phosphatase 1 (SAP-1) is a receptor-type protein tyrosine phosphatase that is specifically expressed on the apical membrane of the intestinal epithelium. SAP-1 is known to maintain the balance of phosphorylation of proteins together with protein kinases, however, its biological function and impact on pharmacokinetics in the intestine remain unclear. The present study, therefore, aimed to clarify the relationship between SAP-1 and the intestinal absorption behaviors of typical transporter substrates and macromolecules...
April 18, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28431748/a-benchtop-biorobotic-platform-for-in-vitro-observation-of-muscle-tendon-dynamics-with-parallel-mechanical-assistance-from-an-elastic-exoskeleton
#11
Benjamin D Robertson, Siddarth Vadakkeveedu, Gregory S Sawicki
We present a novel biorobotic framework comprised of a biological muscle-tendon unit (MTU) mechanically coupled to a feedback controlled robotic environment simulation that mimics in vivo inertial/gravitational loading and mechanical assistance from a parallel elastic exoskeleton. Using this system, we applied select combinations of biological muscle activation (modulated with rate-coded direct neural stimulation) and parallel elastic assistance (applied via closed-loop mechanical environment simulation) hypothesized to mimic human behavior based on previously published modeling studies...
March 21, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/28431242/structural-and-functional-analysis-of-a-%C3%AE-2-adrenergic-receptor-complex-with-grk5
#12
Konstantin E Komolov, Yang Du, Nguyen Minh Duc, Robin M Betz, João P G L M Rodrigues, Ryan D Leib, Dhabaleswar Patra, Georgios Skiniotis, Christopher M Adams, Ron O Dror, Ka Young Chung, Brian K Kobilka, Jeffrey L Benovic
The phosphorylation of agonist-occupied G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) functions to turn off G-protein signaling and turn on arrestin-mediated signaling. While a structural understanding of GPCR/G-protein and GPCR/arrestin complexes has emerged in recent years, the molecular architecture of a GPCR/GRK complex remains poorly defined. We used a comprehensive integrated approach of cross-linking, hydrogen-deuterium exchange mass spectrometry (MS), electron microscopy, mutagenesis, molecular dynamics simulations, and computational docking to analyze GRK5 interaction with the β2-adrenergic receptor (β2AR)...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431241/akt-pkb-signaling-navigating-the-network
#13
REVIEW
Brendan D Manning, Alex Toker
The Ser and Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of AKT, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28431233/a-compendium-of-rna-binding-proteins-that-regulate-microrna-biogenesis
#14
Thomas Treiber, Nora Treiber, Uwe Plessmann, Simone Harlander, Julia-Lisa Daiß, Norbert Eichner, Gerhard Lehmann, Kevin Schall, Henning Urlaub, Gunter Meister
During microRNA (miRNA) biogenesis, two endonucleolytic reactions convert stem-loop-structured precursors into mature miRNAs. These processing steps can be posttranscriptionally regulated by RNA-binding proteins (RBPs). Here, we have used a proteomics-based pull-down approach to map and characterize the interactome of a multitude of pre-miRNAs. We identify ∼180 RBPs that interact specifically with distinct pre-miRNAs. For functional validation, we combined RNAi and CRISPR/Cas-mediated knockout experiments to analyze RBP-dependent changes in miRNA levels...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431230/structural-basis-for-guide-rna-processing-and-seed-dependent-dna-targeting-by-crispr-cas12a
#15
Daan C Swarts, John van der Oost, Martin Jinek
The CRISPR-associated protein Cas12a (Cpf1), which has been repurposed for genome editing, possesses two distinct nuclease activities: endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage. To elucidate the molecular basis of both activities, we determined crystal structures of Francisella novicida Cas12a bound to guide RNA and in complex with an R-loop formed by a non-cleavable guide RNA precursor and a full-length target DNA. Corroborated by biochemical experiments, these structures reveal the mechanisms of guide RNA processing and pre-ordering of the seed sequence in the guide RNA that primes Cas12a for target DNA binding...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431135/reconstitution-of-a-functional-7sk-snrnp
#16
John E Brogie, David H Price
The 7SK small nuclear ribonucleoprotein (snRNP) plays a central role in RNA polymerase II elongation control by regulating the availability of active P-TEFb. We optimized conditions for analyzing 7SK RNA by SHAPE and demonstrated a hysteretic effect of magnesium on 7SK folding dynamics including a 7SK GAUC motif switch. We also found evidence that the 5΄ end pairs alternatively with two different regions of 7SK giving rise to open and closed forms that dictate the state of the 7SK motif. We then used recombinant P-TEFb, HEXIM1, LARP7 and MEPCE to reconstruct a functional 7SK snRNP in vitro...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28431120/solution-structure-of-a-reverse-transcriptase-recognition-site-of-a-line-rna-from-zebrafish
#17
Maina Otsu, Masaki Kajikawa, Norihiro Okada, Gota Kawai
Long interspersed nuclear element (LINE) is known to be transposed by reverse transcription using its RNA transcript. Recognition of the 3' stem-loop of LINE RNA by its reverse transcriptase (RT) is an important step of the retrotransposition. Our previous study revealed that the second G residue (G8) in the GGAUA loop of a 17mer LINE RNA from eel, UnaL2-17, is recognized by its RT and the U residue (U10) in the same loop is required to maintain the loop structure (Baba et al., 2004). ZfL2-2, a LINE from zebrafish, has the same 3' stem-loop with UnaL2 and ZfL2-1 has similar but distinct 3' stem-loop with an insertion which can form an additional stem-loop...
April 18, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28430877/the-accessible-chromatin-landscape-during-conversion-of-human-embryonic-stem-cells-to-trophoblast-by-bmp4
#18
Yajun Liu, Dewu Ding, Hongde Liu, Xiao Sun
Human embryonic stem cells (hESC) exposed to the growth factor bone morphogenic protein 4 (BMP4) in the absence of FGF2 have been used as a model to study the development of placental development. However, little is known about the cis-regulatory mechanisms underlying this important process. In this study, we used the public available chromatin accessibility data of hESC H1 cells and BMP4-induced trophoblast (TB)cell lines to identify DNase I hypersensitive sites (DHSs) in the two cell lines, as well as the transcription factor binding sites within the DHSs...
April 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28430783/shigella-dysenteriae-infection-activates-proinflammatory-response-through-%C3%AE-catenin-nf-%C3%AE%C2%BAb-signaling-pathway
#19
Ashidha Gopal, Iyer Soumya Chidambaram, Niranjali Devaraj, Halagowder Devaraj
Shigella dysenteriae (S.dysenteriae) the causative agent of bacillary dysentery invades the human colonic epithelium resulting in severe intestinal inflammatory response and epithelial destruction. However, the mechanism by which S.dysenteriae infection regulates proinflammatory cytokines during intestinal inflammation is still obscure. In this study, we evaluated whether the interaction of β-catenin and NF-κB regulates proinflammatory cytokines TNF-α and IL-8 by modulating GSK-3β activity during S.dysenteriae infection in rat ileal loop model...
2017: PloS One
https://www.readbyqxmd.com/read/28430652/inflammatory-factor-tnf-%C3%AE-promotes-the-growth-of-breast-cancer-via-the-positive-feedback-loop-of-tnfr1-nf-%C3%AE%C2%BAb-and-or-p38-p-stat3-hbxip-tnfr1
#20
Xiaoli Cai, Can Cao, Jiong Li, Fuquan Chen, Shuqin Zhang, Bowen Liu, Weiying Zhang, Xiaodong Zhang, Lihong Ye
In the connection between inflammation and cancer development, tumor necrosis factor-alpha (TNF-α) contributes to the tumorigenesis. However, the underlying mechanism remains poorly understood. In this study, we report that TNF-α enhances the growth of breast cancer through up-regulation of oncoprotein hepatitis B X-interacting protein (HBXIP). Our data showed that the levels of TNF-α were positively related to those of HBXIP in clinical breast cancer tissues. Moreover, TNF-α could up-regulate HBXIP in breast cancer cells...
April 6, 2017: Oncotarget
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