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https://www.readbyqxmd.com/read/28723415/pharmacology-of-human-trace-amine-associated-receptors-therapeutic-opportunities-and-challenges
#1
REVIEW
Mark D Berry, Raul R Gainetdinov, Marius C Hoener, Mohammed Shahid
The discovery in 2001 of a G protein-coupled receptor family, subsequently termed trace amine-associated receptors (TAAR), triggered a resurgence of interest in so-called trace amines. Initial optimism quickly faded, however, as the TAAR family presented a series of challenges preventing the use of standard medicinal chemistry and pharmacology technologies. Consequently the development of basic tools for probing TAAR and translating findings from model systems to humans has been problematic. Despite these challenges the last 5 years have seen considerable advances, in particular with respect to TAAR1, which appears to function as an endogenous rheostat, maintaining central neurotransmission within defined physiological limits, in part through receptor heterodimerization yielding biased signaling outputs...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28720428/inhibitors-of-connexin-and-pannexin-channels-as-potential-therapeutics
#2
REVIEW
Joost Willebrords, Michaël Maes, Sara Crespo Yanguas, Mathieu Vinken
While gap junctions support the exchange of a number of molecules between neighboring cells, connexin hemichannels provide communication between the cytosol and the extracellular environment of an individual cell. The latter equally holds true for channels composed of pannexin proteins, which display an architecture reminiscent of connexin hemichannels. In physiological conditions, gap junctions are usually open, while connexin hemichannels and, to a lesser extent, pannexin channels are typically closed, yet they can be activated by a number of pathological triggers...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28720171/pacbio-assembly-of-a-plasmodium-knowlesi-genome-sequence-with-hi-c-correction-and-manual-annotation-of-the-sicavar-gene-family
#3
S A Lapp, J A Geraldo, J-T Chien, F Ay, S B Pakala, G Batugedara, J Humphrey, J D DeBARRY, K G Le Roch, M R Galinski, J C Kissinger
Plasmodium knowlesi has risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout South East Asia. The P. knowlesi genome sequence generated in 2008 highlighted and confirmed many similarities and differences in Plasmodium species, including a global view of several multigene families, such as the large SICAvar multigene family encoding the variant antigens known as the schizont-infected cell agglutination proteins. However, repetitive DNA sequences are the bane of any genome project, and this and other Plasmodium genome projects have not been immune to the gaps, rearrangements and other pitfalls created by these genomic features...
July 19, 2017: Parasitology
https://www.readbyqxmd.com/read/28716730/interaction-of-small-g-protein-signaling-modulator-3-with-connexin-43-contributes-to-myocardial-infarction-in-rat-hearts
#4
Chang Youn Lee, Jung-Won Choi, Sunhye Shin, Jiyun Lee, Hyang-Hee Seo, Soyeon Lim, Seahyoung Lee, Hyun-Chul Joo, Sang Woo Kim, Ki-Chul Hwang
Connexin 43 (Cx43), a ubiquitous connexin expressed in the heart and skin, is associated with a variety of hereditary conditions. Therefore, the characterization of Cx43-interacting proteins and their dynamics is important to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication but also to identify novel and unanticipated biological functions of Cx43. In the present study, we observed potential targets of Cx43 to determine new molecular functions in cardio-protection...
July 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28715970/scaffold-in-scaffold-potential-to-induce-growth-and-differentiation-of-cardiac-progenitor-cells
#5
Matteo Ciocci, Federico Mochi, Felicia Carotenuto, Emilia Di Giovanni, Paolo Prosposito, Roberto Francini, Fabio De Matteis, Igor Reshetov, Mauro Casalboni, Sonia Melino, Paolo Di Nardo
The design of reliable biocompatible and biodegradable scaffolds remains one of the most important challenges for tissue engineering. In fact, properly designed scaffolds must display an adequate and interconnected porosity to facilitate cell spreading and colonization of the inner layers, and must release physical signals concurring to modulate cell function to ultimately drive cell fate. In the present study, a combination of optimal mechanical and biochemical properties has been considered to design a one-component 3D multitextured hydrogel scaffold in order to favor cell-scaffold interactions...
July 17, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28715203/a-bioinorganic-approach-to-fragment-based-drug-discovery-targeting-metalloenzymes
#6
Seth M Cohen
Metal-dependent enzymes (i.e., metalloenzymes) make up a large fraction of all enzymes and are critically important in a wide range of biological processes, including DNA modification, protein homeostasis, antibiotic resistance, and many others. Consequently, metalloenzymes represent a vast and largely untapped space for drug development. The discovery of effective therapeutics that target metalloenzymes lies squarely at the interface of bioinorganic and medicinal chemistry and requires expertise, methods, and strategies from both fields to mount an effective campaign...
July 17, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28714698/microrna-intercellular-transfer-and-bioelectrical-regulation-of-model-multicellular-ensembles-by-the-gap-junction-connectivity
#7
Javier Cervera, Salvador Meseguer, Salvador Mafe
We have studied theoretically the microRNA (miRNA) intercellular transfer through voltage-gated gap junctions in terms of a biophysically-grounded system of coupled differential equations. Instead of modeling a specific system, we use a general approach describing the interplay between the genetic mechanisms and the single-cell electric potentials. The dynamics of the multicellular ensemble are simulated under different conditions including spatially-inhomogeneous transcription rates and local intercellular transfer of miRNAs...
July 17, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28713376/myristoylation-an-important-protein-modification-in-the-immune-response
#8
REVIEW
Daniel Ikenna Udenwobele, Ruey-Chyi Su, Sara V Good, Terry Blake Ball, Shailly Varma Shrivastav, Anuraag Shrivastav
Protein N-myristoylation is a cotranslational lipidic modification specific to the alpha-amino group of an N-terminal glycine residue of many eukaryotic and viral proteins. The ubiquitous eukaryotic enzyme, N-myristoyltransferase, catalyzes the myristoylation process. Precisely, attachment of a myristoyl group increases specific protein-protein interactions leading to subcellular localization of myristoylated proteins with its signaling partners. The birth of the field of myristoylation, a little over three decades ago, has led to the understanding of the significance of protein myristoylation in regulating cellular signaling pathways in several biological processes especially in carcinogenesis and more recently immune function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28713355/respiratory-pathways-reconstructed-by-multi-omics-analysis-in-melioribacter-roseus-residing-in-a-deep-thermal-aquifer-of-the-west-siberian-megabasin
#9
Sergey Gavrilov, Olga Podosokorskaya, Dmitry Alexeev, Alexander Merkel, Maria Khomyakova, Maria Muntyan, Ilya Altukhov, Ivan Butenko, Elizaveta Bonch-Osmolovskaya, Vadim Govorun, Ilya Kublanov
Melioribacter roseus, a representative of recently proposed Ignavibacteriae phylum, is a metabolically versatile thermophilic bacterium, inhabiting subsurface biosphere of the West-Siberian megabasin and capable of growing on various substrates and electron acceptors. Genomic analysis followed by inhibitor studies and membrane potential measurements of aerobically grown M. roseus cells revealed the activity of aerobic respiratory electron transfer chain comprised of respiratory complexes I and IV, and an alternative complex III...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28712848/a-short-region-of-connexin43-reduces-human-glioma-stem-cell-migration-invasion-and-survival-through-src-pten-and-fak
#10
Myriam Jaraíz-Rodríguez, Ma Dolores Tabernero, María González-Tablas, Alvaro Otero, Alberto Orfao, Jose M Medina, Arantxa Tabernero
Connexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here, we show that a cell-penetrating peptide based on CX43 (TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients...
July 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28712408/-dectection-of-g3bp-and-cd44v6-in-the-tissues-of-laryngeal-squamous-cell-carcinoma-and-their-clinical-significance
#11
Dahu Luo, Weihua Lou
Objective To study the expressions of RNA-binding Ras-GAP SH3 binding protein (G3BP) and tumor stem cell marker CD44v6 in laryngeal squamous cell carcinoma and their correlations with angiogenesis. Methods We collected the cancer tissues and corresponding paracancerous tissues from 56 patients with laryngeal squamous cell carcinoma. The expressions of G3BP and CD44v6 proteins were detected by Western blotting in cancer tissues and corresponding paracancerous tissues; the expressions of G3BP, CD44v6 and vascular endothelial growth factor A (VEGF-A) were tested by immunohistochemistry...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28712094/different-mutations-of-gap-junction-connexin-47-lead-to-discrepant-activation-of-unfolded-protein-response-pathway-in-pelizaeus-merzbacher-like-disease
#12
Na Chen, Jingmin Wang, Yuwu Jiang, Ye Wu, Hongjun Hao, Taoyun Ji
No abstract text is available yet for this article.
July 16, 2017: Neuropediatrics
https://www.readbyqxmd.com/read/28711732/high-level-expression-and-purification-of-a-mollusca-endoglucanase-from-ampullaria-crossean-in-pichia-pastoris
#13
Xiuping Su, Xinwei Geng, Meixian Fu, Yeqing Wu, Longfei Yin, Fukun Zhao, Wei Chen
EG27I is an endogenous glucanase belonging to glycoside hydrolase family (GHF) 45 from the Mollusca, Ampullaria crossean. In this study, the EG27I mature peptide gene fused to HFBII secretion signal of Trichoderma reesei was expressed under GAP promoter of Pichia pastoris in SMD1163 strain. Bioactive EG27I with a molecular weight of 27 kDa was successfully expressed and secreted into the culture medium. When high cell density fermentation of the recombinant Pichia pastoris was performed by a fed-batch strategy for totally 132 h in a 7...
July 12, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28710348/spatiotemporal-expression-patterns-of-wheat-amino-acid-transporters-reveal-their-putative-roles-in-nitrogen-transport-and-responses-to-abiotic-stress
#14
Yongfang Wan, Robert King, Rowan A C Mitchell, Keywan Hassani-Pak, Malcolm J Hawkesford
Amino acid transporters have roles in amino acid uptake from soil, long-distance transport, remobilization from vegetative tissues and accumulation in grain. Critically, the majority of wheat grain nitrogen is derived from amino acids remobilized from vegetative organs. However, no systematic analysis of wheat AAT genes has been reported to date. Here, 283 full length wheat AAT genes representing 100 distinct groups of homeologs were identified and curated by selectively consolidating IWGSC CSSv2 and TGACv1 Triticum aestivum genome assemblies and reassembling or mapping of IWGSC CSS chromosome sorted reads to fill any gaps...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709956/activation-of-human-gonadotropin-releasing-hormone-receptor-promotes-down-regulation-of-arhgap18-and-regulates-the-cell-invasion-of-mda-mb-231%C3%A2-cells
#15
Arturo Aguilar-Rojas, Guadalupe Maya-Núñez, Maira Huerta-Reyes, Marco Allán Pérez-Solis, Raúl Silva-García, Nancy Guillén, Jean-Christophe Olivo-Marin
The Gonadotropin-Releasing Hormone Receptor (GnRHR) is expressed mainly in the gonadotrope membrane of the adenohypophysis and its natural ligand, the Gonadotropin-Releasing Hormone (GnRH), is produced in anterior hypothalamus. Furthermore, both molecules are also present in the membrane of cells derived from other reproductive tissues such as the breast, endometrium, ovary, and prostate, as well as in tumors derived from these tissues. The functions of GnRH receptor and its hormone in malignant cells have been related with the decrease of proliferation and the invasiveness of those tumors however, little is known about the molecules associated with the signaling pathways regulated by both molecules in malignant cells...
July 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28708375/enzyme-that-makes-you-cry-crystal-structure-of-lachrymatory-factor-synthase-from-allium-cepa
#16
Josie A Silvaroli, Matthew J Pleshinger, Surajit Banerjee, Philip D Kiser, Marcin Golczak
The biochemical pathway that gives onions their savor is part of the chemical warfare against microbes and animals. This defense mechanism involves formation of a volatile lachrymatory factor (LF) ((Z)-propanethial S-oxide) that causes familiar eye irritation associated with onion chopping. LF is produced in a reaction catalyzed by lachrymatory factor synthase (LFS). The principles by which LFS facilitates conversion of a sulfenic acid substrate into LF have been difficult to experimentally examine owing to the inherent substrate reactivity and lability of LF...
July 14, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28706505/cell-cell-interaction-proteins-gap-junctions-tight-junctions-and-desmosomes-and-water-transporter-aquaporin-4-in-meningothelial-cells-of-the-human-optic-nerve
#17
Thi Ngoc Co Zeleny, Corina Kohler, Albert Neutzner, Hanspeter E Killer, Peter Meyer
PURPOSE: Meningothelial cells (MECs) play a central role in the maintenance of cerebrospinal fluid (CSF) homeostasis and in physiological and pathophysiological processes within the subarachnoid space (SAS) linking them to optic nerve (ON) pathologies. Still, not much is known about their structural properties that might enable MECs to perform specific functions within the ON microenvironment. METHODS: For closer characterization of the structural properties of the human MEC layer in the arachnoid, we performed immunohistological analyses to evaluate the presence of cell-cell interaction markers, namely, markers for tight junctions (JAM1, Occludin, and Claudin 5), gap junctions (Connexin 26 and 43), and desmosomes (Desmoplakin) as well as for water channel marker aquaporin 4 (AQP4) in retrobulbar, midorbital, and intracanalicular human ON sections...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28706245/connexin-50-functions-as-an-adhesive-molecule-and-promotes-lens-cell-differentiation
#18
Zhengping Hu, Wen Shi, Manuel A Riquelme, Qian Shi, Sondip Biswas, Woo-Kuen Lo, Thomas W White, Sumin Gu, Jean X Jiang
Connexins play essential roles in lens homeostasis and development. Here, we identified a new role for Cx50 that mediates cell-cell adhesion function. Cx50 enhanced the adhesive capability of AQP0. Interestingly, the expression of Cx50 alone promoted cell adhesion at a comparable level to AQP0; however, this cell adhesive function was not observed with other lens connexins, Cx43 and Cx46. Moreover, the adhesive property occurred in both homotypic with Cx50 expressed in both pairing cells and heterotypic with Cx50 in only one pairing cell, and this function appears to be unrelated to its role in forming gap junction channels...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28706196/synaptic-gap-and-gef-complexes-cluster-proteins-essential-for-gtp-signaling
#19
Brent Wilkinson, Jing Li, Marcelo P Coba
GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs) play essential roles in regulating the activity of small GTPases. Several GAPs and GEFs have been shown to be present at the postsynaptic density (PSD) within excitatory glutamatergic neurons and regulate the activity of glutamate receptors. However, it is not known how synaptic GAP and GEF proteins are organized within the PSD signaling machinery, if they have overlapping interaction networks, or if they associate with proteins implicated in contributing to psychiatric disease...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705239/nap-the-network-analysis-profiler-a-web-tool-for-easier-topological-analysis-and-comparison-of-medium-scale-biological-networks
#20
Theodosios Theodosiou, Georgios Efstathiou, Nikolas Papanikolaou, Nikos C Kyrpides, Pantelis G Bagos, Ioannis Iliopoulos, Georgios A Pavlopoulos
OBJECTIVE: Nowadays, due to the technological advances of high-throughput techniques, Systems Biology has seen a tremendous growth of data generation. With network analysis, looking at biological systems at a higher level in order to better understand a system, its topology and the relationships between its components is of a great importance. Gene expression, signal transduction, protein/chemical interactions, biomedical literature co-occurrences, are few of the examples captured in biological network representations where nodes represent certain bioentities and edges represent the connections between them...
July 14, 2017: BMC Research Notes
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