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Non-structural protein 1

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https://www.readbyqxmd.com/read/29149835/forkhead-transcription-factors-formulating-a-foxo-target-for-cognitive-loss
#1
Kenneth Maiese
BACKGROUND: With almost 47 million individuals worldwide suffering from some aspect of dementia, it is clear that cognitive loss impacts a significant proportion of the global population. Unfortunately, definitive treatments to resolve or prevent the onset of cognitive loss are limited. In most cases such care is currently non-existent prompting the need for novel treatment strategies. METHODS: Mammalian forkhead transcription factors of the O class (FoxO) are one such avenue of investigation that offer an exciting potential to bring new treatments forward for disorders that involve cognitive loss...
November 15, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/29148740/effect-of-an-imposed-contact-on-secondary-structure-in-the-denatured-state-of-yeast-iso-1-cytochome-c
#2
Travis A Danielson, Jessica M Stine, Tanveer A Dar, Klara Briknarova, Bruce E Bowler
There is considerable evidence that long-range interactions stabilize residual protein structure under denaturing conditions. However, evaluation of the effect of a specific contact on structure in the denatured state has been difficult. Iso-1-cytochrome c variants with a Lys54-->His mutation form a particularly stable His-heme loop in the denatured state, suggestive of loop-induced residual structure. We have used multidimensional NMR methods to assign (1)H and (15)N backbone amide and (13)C backbone and side chain chemical shifts in the denatured state of iso-1-cytochrome c carrying the Lys54-->His mutation in 3 and 6 M guanidine hydrochloride and at both pH 6...
November 17, 2017: Biochemistry
https://www.readbyqxmd.com/read/29147009/mitochondrial-uqcrb-as-a-new-molecular-prognostic-biomarker-of-human-colorectal-cancer
#3
Hyun-Chul Kim, Junghwa Chang, Hannah S Lee, Ho Jeong Kwon
Ubiquinol cytochrome c reductase binding protein (UQCRB) is important for mitochondrial complex III stability, electron transport, cellular oxygen sensing and angiogenesis. However, its potential as a prognostic marker in colorectal cancer (CRC) remains unclear. The aim of this study was to determine whether UQCRB can be used as a diagnostic molecular marker for CRC. The correlation between the expression of three genes (UQCRB, UQCRFS1 and MT-CYB) in the mitochondrial respiratory chain complex III and clinico-pathological features was determined...
November 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29145933/quantitative-structure-pharmacokinetics-relationships-for-plasma-protein-binding-of-basic-drugs
#4
Zvetanka Dobreva Zhivkova
PURPOSE: Binding of drugs to plasma proteins is a common physiological occurrence which may have a profound effect on both pharmacokinetics and pharmacodynamics. The early prediction of plasma protein binding (PPB) of new drug candidates is an important step in drug development process. The present study is focused on the development of quantitative structure - pharmacokinetics relationship (QSPkR) for the negative logarithm of the free fraction of the drug in plasma (pfu) of basic drugs...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29140585/timap-the-versatile-protein-phosphatase-1-regulator-in-endothelial-cells
#5
REVIEW
Anita Boratkó, Csilla Csortos
Transforming growth factor (TGF)-β inhibited membrane associated protein, TIMAP, is the member of the myosin phosphatase targeting protein (MYPT) family of protein phosphatase 1 (PP1) regulatory subunits. The N-terminal part of TIMAP has a typical MYPT family structure with a sequence element called MyPhone (myosin phosphatase N-terminal element), a putative bipartite nuclear localization signal, a PP1 catalytic subunit binding motif, and five ankyrin repeats. The C-terminal half of TIMAP is intrinsically disordered, but ends with a functional CAAX box for lipid modification which allows localization of TIMAP at the plasma membrane...
November 15, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29138829/resveratrol-ameliorates-inflammatory-damage-and-protects-against-osteoarthritis-in-a-rat-model-of-osteoarthritis
#6
Yulong Wei, Jie Jia, Xin Jin, Wei Tong, Hongtao Tian
Resveratrol is a non‑flavonoid polyphenol compound with a stilbene structure. As a type of phytoalexin produced under stress in plants, it improves the plant's resistance against pathogens and environment deterioration, and performs important functions beneficial to human health, such as anti‑cancer, anti‑oxidation, regulating blood lipid levels and prolonging life span. The effects of resveratrol were examined in a rat model of osteoarthritis (OA) and observed to ameliorate inflammatory damage and protect against OA...
November 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138824/genetic-mutational-testing-of-chinese-children-with-familial-hematuria-with-biopsy%C3%A2-proven-fsgs
#7
Yongzhen Li, Ying Wang, Qingnan He, Xiqiang Dang, Yan Cao, Xiaochuan Wu, Shuanghong Mo, Xiaoxie He, Zhuwen Yi
Focal segmental glomerulosclerosis (FSGS) is a pathological lesion rather than a disease, with a diverse etiology. FSGS may result from genetic and non‑genetic factors. FSGS is considered a podocyte disease due to the fact that in the majority of patients with proven‑FSGS, the lesion results from defects in the podocyte structure or function. However, FSGS does not result exclusively from podocyte‑associated genes, however also from other genes including collagen IV‑associated genes. Patients who carry the collagen type IVA3 chain (COL4A3) or COL4A4 mutations usually exhibit Alport Syndrome (AS), thin basement membrane neuropathy or familial hematuria (FH)...
November 10, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138229/genomic-structural-variations-lead-to-dysregulation-of-important-coding-and-non-coding-rna-species-in-dilated-cardiomyopathy
#8
Jan Haas, Stefan Mester, Alan Lai, Karen S Frese, Farbod Sedaghat-Hamedani, Elham Kayvanpour, Tobias Rausch, Rouven Nietsch, Jes-Niels Boeckel, Avisha Carstensen, Mirko Völkers, Carsten Dietrich, Dietmar Pils, Ali Amr, Daniel B Holzer, Diana Martins Bordalo, Daniel Oehler, Tanja Weis, Derliz Mereles, Sebastian Buss, Eva Riechert, Emil Wirsz, Maximilian Wuerstle, Jan O Korbel, Andreas Keller, Hugo A Katus, Andreas E Posch, Benjamin Meder
The transcriptome needs to be tightly regulated by mechanisms that include transcription factors, enhancers, and repressors as well as non-coding RNAs. Besides this dynamic regulation, a large part of phenotypic variability of eukaryotes is expressed through changes in gene transcription caused by genetic variation. In this study, we evaluate genome-wide structural genomic variants (SVs) and their association with gene expression in the human heart. We detected 3,898 individual SVs affecting all classes of gene transcripts (e...
November 14, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29137867/functionalized-2-1-benzothiazine-2-2-dioxides-as-new-inhibitors-of-dengue-ns5-rna-dependent-rna-polymerase
#9
Rolando Cannalire, Delia Tarantino, Andrea Astolfi, Maria Letizia Barreca, Stefano Sabatini, Serena Massari, Oriana Tabarrini, Mario Milani, Gilles Querat, Eloise Mastrangelo, Giuseppe Manfroni, Violetta Cecchetti
Over recent years, many RNA viruses have been "re-discovered", including life-threatening flaviviruses, such as Dengue, Zika, and several encephalitis viruses. Since no specific inhibitors are currently available to treat these infections, there is a pressing need for new therapeutics. Among the flaviviral proteins, NS5 RNA-dependent RNA polymerase (RdRp) represents a validated target being essential for viral replication and it has no human analog. To date, few NS5 RdRp inhibitor chemotypes have been reported and no inhibitors are currently in clinical development...
November 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29137637/molecular-evolution-of-hiv-1-integrase-during-the-20%C3%A2-years-prior-to-the-first-approval-of-integrase-inhibitors
#10
Karolin Meixenberger, Kaveh Pouran Yousef, Maureen Rebecca Smith, Sybille Somogyi, Stefan Fiedler, Barbara Bartmeyer, Osamah Hamouda, Norbert Bannert, Max von Kleist, Claudia Kücherer
BACKGROUND: Detailed knowledge of the evolutionary potential of polymorphic sites in a viral protein is important for understanding the development of drug resistance in the presence of an inhibitor. We therefore set out to analyse the molecular evolution of the HIV-1 subtype B integrase at the inter-patient level in Germany during a 20-year period prior to the first introduction of integrase strand inhibitors (INSTIs). METHODS: We determined 337 HIV-1 integrase subtype B sequences (amino acids 1-278) from stored plasma samples of antiretroviral treatment-naïve individuals newly diagnosed with HIV-1 between 1986 and 2006...
November 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/29136098/sequential-search-leads-to-faster-more-efficient-fragment-based-de-novo-protein-structure-prediction
#11
Saulo H P de Oliveira, Eleanor C Law, Jiye Shi, Charlotte M Deane
Motivation: Most current de novo structure prediction methods randomly sample protein conformations and thus require large amounts of computational resource. Here, we consider a sequential sampling strategy, building on ideas from recent experimental work which shows that many proteins fold cotranslationally. Results: We have investigated whether a pseudo-greedy search approach, which begins sequentially from one of the termini, can improve the performance and accuracy of de novo protein structure prediction...
November 9, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29134494/expression-of-telomere-associated-proteins-is-interdependent-to-stabilize-native-telomere-structure-and-telomere-dysfunction-by-g-quadruplex-ligand-causes-terra-upregulation
#12
Ratan Sadhukhan, Priyanka Chowdhury, Sourav Ghosh, Utpal Ghosh
Telomere DNA can form specialized nucleoprotein structure with telomere-associated proteins to hide free DNA ends or G-quadruplex structures under certain conditions especially in presence of G-quadruplex ligand. Telomere DNA is transcribed to form non-coding telomere repeat-containing RNA (TERRA) whose biogenesis and function is poorly understood. Our aim was to find the role of telomere-associated proteins and telomere structures in TERRA transcription. We silenced four [two shelterin (TRF1, TRF2) and two non-shelterin (PARP-1, SLX4)] telomere-associated genes using siRNA and verified depletion in protein level...
November 13, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29133046/design-synthesis-and-biological-evaluation-of-novel-benzimidazole-amidines-as-potent-multi-target-inhibitors-for-the-treatment-of-non-small-cell-lung-cancer
#13
Andrea Bistrović, Luka Krstulović, Anja Harej, Petra Grbčić, Mirela Sedić, Sanja Koštrun, Sandra Kraljević Pavelić, Miroslav Bajić, Silvana Raić-Malić
A series of novel amidino 2-substituted benzimidazoles linked to 1,4-disubstituted 1,2,3-triazoles were synthesized by implementation of microwave and ultrasound irradiation in click reaction and subsequent condensation of thus obtained 4-(1,2,3-triazol-1-yl)benzaldehyde with o-phenylenediamines. In vitro antiproliferative screening of compounds performed on human cancer cell lines revealed that p-chlorophenyl-substituted 1,2,3-triazolyl N-isopropylamidine 10c and benzyl-substituted 1,2,3-triazolyl imidazoline 11f benzimidazoles had selective and potent cytostatic activities in the low nM range against non-small cell lung cancer cell line A549, which could be attributed to induction of apoptosis and primary necrosis...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29131935/the-x-ray-structure-of-catenated-lytic-transglycosylase-sltb1
#14
Teresa Domínguez-Gil, Rafael Molina, David A Dik, Edward Spink, Shahriar Mobashery, Juan A Hermoso
Formation of catenanes by proteins is rare, with few examples known. We report herein the X-ray structure of a catenane dimer of the lytic transglycosylase SltB1 of Pseudomonas aeruginosa. The enzyme is soluble and exists in the periplasmic space, where it modifies bacterial cell wall. The catenane dimer exhibits the protein monomers in a non-covalent chain-link arrangement, whereby a stretch of 51 amino acids (to become a loop and three helices) from one monomer threads through the central opening of the structure of the partner monomer...
November 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/29128390/nsp3-of-coronaviruses-structures-and-functions-of-a-large-multi-domain-protein
#15
REVIEW
Jian Lei, Yuri Kusov, Rolf Hilgenfeld
The multi-domain non-structural protein 3 (Nsp3) is the largest protein encoded by the coronavirus (CoV) genome, with an average molecular mass of about 200 kD. Nsp3 is an essential component of the replication/transcription complex. It comprises various domains, the organization of which differs between CoV genera, due to duplication or absence of some domains. However, eight domains of Nsp3 exist in all known CoVs: the ubiquitin-like domain 1 (Ubl1), the Glu-rich acidic domain (also called "hypervariable region"), a macrodomain (also named "X domain"), the ubiquitin-like domain 2 (Ubl2), the papain-like protease 2 (PL2(pro)), the Nsp3 ectodomain (3Ecto, also called "zinc finger domain"), as well as the domains Y1 and CoV-Y of unknown functions...
November 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29127427/amniotic-membrane-promotes-focal-adhesion-remodeling-to-stimulate-cell-migration
#16
Ángel Bernabé-García, Sergio Liarte, Jose M Moraleda, Gregorio Castellanos, Francisco J Nicolás
During wound healing, the migration of keratinocytes onto newly restored extracellular matrix aims to reestablish continuity of the epidermis. The application of amniotic membrane (AM) to chronic, deep traumatic, non-healing wounds has proven successful at stimulating re-epithelialization. When applied on epithelial cell cultures, AM activates extracellular signal-regulated kinases 1/2 (ERK1/2) and c-Jun N-terminal kinases 1/2 (JNK1/2), with the overexpression and phosphorylation of c-Jun along the wound edge...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29126780/identification-of-protein-w-the-elusive-sixth-subunit-of-the-rhodopseudomonas-palustris-reaction-center-light-harvesting-1-core-complex
#17
Philip J Jackson, Andrew Hitchcock, David J K Swainsbury, Pu Qian, Elizabeth C Martin, David A Farmer, Mark J Dickman, Daniel P Canniffe, C Neil Hunter
The X-ray crystal structure of the Rhodopseudomonas (Rps.) palustris reaction center-light harvesting 1 (RC-LH1) core complex revealed the presence of a sixth protein component, variably referred to in the literature as helix W, subunit W or protein W. The position of this protein prevents closure of the LH1 ring, possibly to allow diffusion of ubiquinone/ubiquinol between the RC and the cytochrome bc1 complex in analogous fashion to the well-studied PufX protein from Rhodobacter sphaeroides. The identity and function of helix W have remained unknown for over 13 years; here we use a combination of biochemistry, mass spectrometry, molecular genetics and electron microscopy to identify this protein as RPA4402 in Rps...
November 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29126766/raman-spectroscopic-analysis-of-oral-cells-in-the-high-wavenumber-region
#18
Luis Felipe C S Carvalho, Franck Bonnier, Cláudio Tellez, Laurita Dos Santos, Kate O'Callaghan, Jeff O'Sullivan, Luis Eduardo S Soares, Stephen Flint, Airton A Martin, Fiona M Lyng, Hugh J Byrne
Raman spectroscopy can provide a molecular-level signature of the biochemical composition and structure of cells with submicrometer spatial resolution and could be useful to monitor changes in composition for early stage and non-invasive cancer diagnosis, both ex-vivo and in vivo. In particular, the fingerprint spectral region (400-1800cm(-1)) has been shown to be very promising for optical biopsy purposes. However, limitations for discrimination of dysplastic and inflammatory processes based on the fingerprint region have been demonstrated...
November 7, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29126140/zona-pellucida-binding-protein-2-zpbp2-and-several-proteins-containing-bx7b-motifs-in-human-sperm-may-have-hyaluronic-acid-binding-or-recognition-properties
#19
F Torabi, O A Bogle, J M Estanyol, R Oliva, D Miller
STUDY QUESTION: Are there novel hyaladherins in human sperm? SUMMARY ANSWER: Zona pellucida-binding protein 2 (ZPBP2), containing a Link-like hyaluronic acid (HA)-binding domain, and several other proteins containing BX7B motifs, such as ADAM32 and Midkine, may be novel hyaladherins with HA-binding properties. WHAT IS KNOWN ALREADY: HA-binding proteins (hyaladherins), which can bind HA surrounding the cumulus-oophorus complex, are distinct from hyases such as PH 20 (SPAM1) and are expressed by mature spermatozoa...
November 8, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29123681/lifetimes-and-spatio-temporal-response-of-protein-crystals-in-intense-x-ray-microbeams
#20
Matthew A Warkentin, Hakan Atakisi, Jesse B Hopkins, Donald Walko, Robert E Thorne
Serial synchrotron-based crystallography using intense microfocused X-ray beams, fast-framing detectors and protein microcrystals held at 300 K promises to expand the range of accessible structural targets and to increase overall structure-pipeline throughputs. To explore the nature and consequences of X-ray radiation damage under microbeam illumination, the time-, dose- and temperature-dependent evolution of crystal diffraction have been measured with maximum dose rates of 50 MGy s(-1). At all temperatures and dose rates, the integrated diffraction intensity for a fixed crystal orientation shows non-exponential decays with dose...
November 1, 2017: IUCrJ
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