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https://www.readbyqxmd.com/read/29031163/ebola-virus-requires-phosphatidylinositol-3-5-bisphosphate-production-for-efficient-viral-entry
#1
Shirley Qiu, Anders Leung, Yuxia Bo, Robert A Kozak, Sai Priya Anand, Corina Warkentin, Fabiola D R Salambanga, Jennifer Cui, Gary Kobinger, Darwyn Kobasa, Marceline Côté
For entry, Ebola virus (EBOV) requires the interaction of its viral glycoprotein with the cellular protein Niemann-Pick C1 (NPC1) which resides in late endosomes and lysosomes. How EBOV is trafficked and delivered to NPC1 and whether this is positively regulated during entry remain unclear. Here, we show that the PIKfyve-ArPIKfyve-Sac3 cellular complex, which is involved in the metabolism of phosphatidylinositol (3,5) bisphosphate (PtdIns(3,5)P2), is critical for EBOV infection. Although the expression of all subunits of the complex was required for efficient entry, PIKfyve kinase activity was specifically critical for entry by all pathogenic filoviruses...
October 11, 2017: Virology
https://www.readbyqxmd.com/read/29031045/structural-characterization-of-the-man5-glycoform-of-human-igg3-fc
#2
Ishan S Shah, Scott Lovell, Nurjahan Mehzabeen, Kevin P Battaile, Thomas J Tolbert
Immunoglobulin G (IgG) consists of four subclasses in humans: IgG1, IgG2, IgG3 and IgG4, which are highly conserved but have unique differences that result in subclass-specific effector functions. Though IgG1 is the most extensively studied IgG subclass, study of other subclasses is important to understand overall immune function and for development of new therapeutics. When compared to IgG1, IgG3 exhibits a similar binding profile to Fcγ receptors and stronger activation of complement. All IgG subclasses are glycosylated at N297, which is required for Fcγ receptor and C1q complement binding as well as maintaining optimal Fc conformation...
October 11, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29031033/an-arabidopsis-divergent-pumilio-protein-apum24-is-essential-for-embryogenesis-and-required-for-faithful-pre-rrna-processing
#3
Thiruvenkadam Shanmugam, Nazia Abbasi, Hyung-Sae Kim, Ho Bang Kim, Nam-Il Park, Guen Tae Park, Sung Aeong Oh, Soon Ki Park, Douglas G Muench, Yeonhee Choi, Youn-Il Park, Sang-Bong Choi
Pumilio RNA-binding proteins are largely involved in mRNA degradation and translation repression. However, a few evolutionarily divergent Pumilios are also responsible for proper pre-rRNA processing in human and yeast. Here, we describe an essential Arabidopsis nucleolar Pumilio, APUM24, that is expressed in tissues undergoing rapid proliferation and cell division. A T-DNA insertion for APUM24 did not affect the male and female gametogenesis, but instead resulted in a negative female gametophytic effect on zygotic cell division immediately after fertilization...
October 14, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29029360/laser-desorption-ionization-mass-spectrometry-recent-progress-in-matrix-free-and-label-assisted-techniques
#4
REVIEW
Arundhoti Mandal, Monisha Singha, Partha Sarathi Addy, Amit Basak
The MALDI-based mass spectrometry, over the last three decades, has become an important analytical tool. It is a gentle ionization technique, usually applicable to detect and characterize analytes with high molecular weights like proteins and other macromolecules. The earlier difficulty of detection of analytes with low molecular weights like small organic molecules and metal ion complexes with this technique arose due to the cluster of peaks in the low molecular weight region generated from the matrix. To detect such molecules and metal ion complexes, a four-prong strategy has been developed...
October 13, 2017: Mass Spectrometry Reviews
https://www.readbyqxmd.com/read/29029246/the-epidermal-growth-factor-network-role-in-oocyte-growth-maturation-and-developmental-competence
#5
Dulama Richani, Robert B Gilchrist
BACKGROUND: The LH surge induces great physiological changes within the preovulatory follicle, which culminate in the ovulation of a mature oocyte that is capable of supporting embryo and foetal development. However, unlike mural granulosa cells, the oocyte and its surrounding cumulus cells are not directly responsive to LH, indicating that the LH signal is mediated by secondary factors produced by the granulosa cells. The mechanisms by which the oocyte senses the ovulatory LH signal and hence prepares for ovulation has been a subject of considerable controversy for the past four decades...
September 20, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/29028891/on-the-mechanisms-of-protein-interactions-predicting-their-affinity-from-unbound-tertiary-structures
#6
Manuel Alejandro Marín-López, Joan Planas-Iglesias, Joaquim Aguirre-Plans, Jaume Bonet, Javier Garcia-Garcia, Narcis Fernandez-Fuentes, Baldo Oliva
Motivation: The characterization of the protein-protein association mechanisms is crucial to understanding how biological processes occur. It has been previously shown that the early formation of non-specific encounters enhances the realization of the stereospecific (i.e. native) complex by reducing the dimensionality of the search process. The association rate for the formation of such complex plays a crucial role in the cell biology and depends on how the partners diffuse to be close to each other...
September 27, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29028835/hydrogen-peroxide-yields-mechanistic-insights-into-human-mrna-capping-enzyme-function
#7
Nicholas J Mullen, David H Price
Capping of nascent RNA polymerase II (Pol II) transcripts is required for gene expression and the first two steps are catalyzed by separate 5' triphosphatase and guanylyltransferase activities of the human capping enzyme (HCE). The cap is added co-transcriptionally, but how the two activities are coordinated is unclear. Our previous in vitro work has suggested that an unidentified factor modulates the minimum length at which nascent transcripts can be capped. Using the same well-established in vitro system with hydrogen peroxide as a capping inhibitor, we show that this unidentified factor targets the guanylyltransferase activity of HCE...
2017: PloS One
https://www.readbyqxmd.com/read/29028833/merkel-cell-polyomavirus-recruits-mycl-to-the-ep400-complex-to-promote-oncogenesis
#8
Jingwei Cheng, Donglim Esther Park, Christian Berrios, Elizabeth A White, Reety Arora, Rosa Yoon, Timothy Branigan, Tengfei Xiao, Thomas Westerling, Alexander Federation, Rhamy Zeid, Benjamin Strober, Selene K Swanson, Laurence Florens, James E Bradner, Myles Brown, Peter M Howley, Megha Padi, Michael P Washburn, James A DeCaprio
Merkel cell carcinoma (MCC) frequently contains integrated copies of Merkel cell polyomavirus DNA that express a truncated form of Large T antigen (LT) and an intact Small T antigen (ST). While LT binds RB and inactivates its tumor suppressor function, it is less clear how ST contributes to MCC tumorigenesis. Here we show that ST binds specifically to the MYC homolog MYCL (L-MYC) and recruits it to the 15-component EP400 histone acetyltransferase and chromatin remodeling complex. We performed a large-scale immunoprecipitation for ST and identified co-precipitating proteins by mass spectrometry...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29028831/short-term-vitamin-e-treatment-impairs-reactive-oxygen-species-signaling-required-for-adipose-tissue-expansion-resulting-in-fatty-liver-and-insulin-resistance-in-obese-mice
#9
Martin Alcala, Maria Calderon-Dominguez, Dolors Serra, Laura Herrero, Maria P Ramos, Marta Viana
OBJECTIVES: The use of antioxidant therapy in the treatment of oxidative stress-related diseases such as cardiovascular disease, diabetes or obesity remains controversial. Our aim is to demonstrate that antioxidant supplementation may promote negative effects if used before the establishment of oxidative stress due to a reduced ROS generation under physiological levels, in a mice model of obesity. METHODS: C57BL/6J mice were fed with a high-fat diet for 14 weeks, with (OE group) or without (O group) vitamin E supplementation...
2017: PloS One
https://www.readbyqxmd.com/read/29028796/bak1-is-involved-in-atralf1-induced-inhibition-of-root-cell-expansion
#10
Keini Dressano, Paulo H O Ceciliato, Aparecida L Silva, Juan Carlos Guerrero-Abad, Tábata Bergonci, Fausto Andrés Ortiz-Morea, Marco Bürger, Marcio C Silva-Filho, Daniel S Moura
The rapid alkalinization factor (RALF) peptide negatively regulates cell expansion, and an antagonistic relationship has been demonstrated between AtRALF1, a root-specific RALF isoform in Arabidopsis, and brassinosteroids (BRs). An evaluation of the response of BR signaling mutants to AtRALF1 revealed that BRI1-associated receptor kinase1 (bak1) mutants are insensitive to AtRALF1 root growth inhibition activity. BAK1 was essential for the induction of AtRALF1-responsive genes but showed no effect on the mobilization of Ca2+ and alkalinization responses...
October 13, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29028573/the-first-protection-free-synthesis-of-magnetic-bifunctional-l-proline-as-a-highly-active-and-versatile-artificial-enzyme-synthesis-of-imidazole-derivatives
#11
Hamideh Aghahosseini, Ali Ramazani, Katarzyna Ślepokura, Tadeusz Lis
l-Proline is a bifunctional versatile organocatalyst that could promote a variety of useful transformations. Some passive and dynamic interactions between this simple amino acid and different substrates, which are necessary to enzymatic reactions, have given it "the simplest enzyme" title. Herein we presented the first report on the synthesis of magnetic bifunctional l-proline as an artificial enzyme without requiring any protection/deprotection steps according to an operationally simple process. This magnetic nano-biocatalyst is a promising catalyst that in a case study was successfully applied for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles in the 70-99% and 60-90% yields respectively, which it could be extended to the variety of l-proline-based organic transformations...
October 6, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29028411/expanding-the-map-of-protein-rna-interaction-sites-via-cell-fusion-followed-by-par-clip
#12
Florian Hinze, Philipp Drewe-Boß, Miha Milek, Uwe Ohler, Markus Landthaler, Michael Gotthardt
PAR-CLIP (photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation) facilitates the identification and mapping of protein/RNA interactions. So far, it has been limited to select cell-lines as it requires efficient 4SU uptake. To increase transcriptome complexity and thus identify additional RNA-protein interaction sites we fused HEK 293 T-Rex cells (HEK293-Y) that express the RNA binding protein YBX1 with PC12 cells expressing eGFP (PC12-eGFP). The resulting hybrids enable PAR-CLIP on a neuronally expanded transcriptome (Fusion-CLIP) and serve as a proof of principle...
October 13, 2017: RNA Biology
https://www.readbyqxmd.com/read/29028184/native-kcc2-interactome-reveals-pacsin1-as-a-critical-regulator-of-synaptic-inhibition
#13
Vivek Mahadevan, C Sahara Khademullah, Zahra Dargaei, Jonah Chevrier, Pavel Uvarov, Julian Kwan, Richard D Bagshaw, Tony Pawson, Andrew Emili, Yves De Koninck, Victor Anggono, Matti Airaksinen, Melanie A Woodin
KCC2 is a neuron-specific K(+)-Cl(-) cotransporter essential for establishing the Cl(-) gradient required for hyperpolarizing inhibition in the central nervous system (CNS). KCC2 is highly localized to excitatory synapses where it regulates spine morphogenesis and AMPA receptor confinement. Aberrant KCC2 function contributes to human neurological disorders including epilepsy and neuropathic pain. Using functional proteomics, we identified the KCC2-interactome in the mouse brain to determine KCC2-protein interactions that regulate KCC2 function...
October 13, 2017: ELife
https://www.readbyqxmd.com/read/29028178/zika-virus-immune-evasion-mechanisms-currently-available-therapeutic-regimens-and-vaccines
#14
Arun Asif, Sobia Manzoor, Fatima Tuz-Zahra, Muhammad Saalim, Maliha Ashraf, Javeria Ishtiyaq, Madiha Khalid
The sudden emergence of infectious pathogens such as Zika virus (ZIKV) holds global health concerns. Recent dissemination of ZIKV from Pacific to Americas with an upsurge of congenital anomalies and Guillain Barre Syndrome (GBS) in adults has created an alarming situation. High-throughput studies are in progress to understand ZIKV's mode of pathogenesis and mechanism of immune escape, yet the pathogenesis remains obscure. Mainly ZIKV's envelope (E) protein and nonstructural proteins (mainly NS1 and NS5) manipulate host cell to support viral immune escape by modulation of the interferon pathway and complement antagonism...
October 13, 2017: Viral Immunology
https://www.readbyqxmd.com/read/29028004/geobiological-feedbacks-and-the-evolution-of-thermoacidophiles
#15
Daniel R Colman, Saroj Poudel, Trinity L Hamilton, Jeff R Havig, Matthew J Selensky, Everett L Shock, Eric S Boyd
Oxygen-dependent microbial oxidation of sulfur compounds leads to the acidification of natural waters. How acidophiles and their acidic habitats evolved, however, is largely unknown. Using 16S rRNA gene abundance and composition data from 72 hot springs in Yellowstone National Park, Wyoming, we show that hyperacidic (pH<3.0) hydrothermal ecosystems are dominated by a limited number of archaeal lineages with an inferred ability to respire O2. Phylogenomic analyses of 584 existing archaeal genomes revealed that hyperacidophiles evolved independently multiple times within the Archaea, each coincident with the emergence of the ability to respire O2, and that these events likely occurred in the recent evolutionary past...
October 13, 2017: ISME Journal
https://www.readbyqxmd.com/read/29027601/dnmt1-dnmt3a-and-dnmt3b-proteins-are-differently-expressed-in-mouse-oocytes-and-early-embryos
#16
Fatma Uysal, Saffet Ozturk, Gokhan Akkoyunlu
DNA methylation is one of the epigenetic mechanisms and plays important roles during oogenesis and early embryo development in mammals. DNA methylation is basically known as adding a methyl group to the fifth carbon atom of cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinucleotide sites. This mechanism is composed of two main processes: de novo methylation and maintenance methylation, both of which are catalyzed by specific DNA methyltransferase (DNMT) enzymes. To date, six different DNMTs have been characterized in mammals defined as DNMT1, DNMT2, DNMT3A, DNMT3B, DNMT3C, and DNMT3L...
October 13, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29027288/cxxc5-expression-in-prostate-cancer-implications-for-cancer-progression
#17
Ines Benedetti, Angelo M De Marzo, Jan Geliebter, Niradiz Reyes
Identification of genes specifically deregulated in prostate adenocarcinoma may lead to discovery of new oncogenes/tumour suppressors with clinical relevance for diagnosis, prognosis and/or therapy. CXXC5 is a gene encoding a retinoid-inducible nuclear factor, whose overexpression in breast tumours, metastatic malignant melanomas and papillary thyroid carcinoma has been recently reported. We previously found differential expression of CXXC5 transcripts in metastatic prostate cancer cell lines of both rat and human origin...
August 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/29027132/submicrometer-emitter-esi-tips-for-native-mass-spectrometry-of-membrane-proteins-in-ionic-and-nonionic-detergents
#18
Anna C Susa, Jennifer L Lippens, Zijie Xia, Joseph A Loo, Iain D G Campuzano, Evan R Williams
Native mass spectrometry (native-MS) of membrane proteins typically requires a detergent screening protocol, protein solubilization in the preferred detergent, followed by protein liberation from the micelle by collisional activation. Here, submicrometer nano-ESI emitter tips are used for native-MS of membrane proteins solubilized in both nonionic and ionic detergent solutions. With the submicrometer nano-ESI emitter tips, resolved charge-state distributions of membrane protein ions are obtained from a 150 mM NaCl, 25 mM Tris-HCl with 1...
October 12, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/29026940/advanced-bioanalytics-for-precision-medicine
#19
Aldo Roda, Elisa Michelini, Cristiana Caliceti, Massimo Guardigli, Mara Mirasoli, Patrizia Simoni
Precision medicine is a new paradigm that combines diagnostic, imaging, and analytical tools to produce accurate diagnoses and therapeutic interventions tailored to the individual patient. This approach stands in contrast to the traditional "one size fits all" concept, according to which researchers develop disease treatments and preventions for an "average" patient without considering individual differences. The "one size fits all" concept has led to many ineffective or inappropriate treatments, especially for pathologies such as Alzheimer's disease and cancer...
October 12, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29026529/coordinating-erk-signaling-via-the-molecular-scaffold-kinase-suppressor-of-ras
#20
REVIEW
Danielle Frodyma, Beth Neilsen, Diane Costanzo-Garvey, Kurt Fisher, Robert Lewis
Many cancers, including those of the colon, lung, and pancreas, depend upon the signaling pathways induced by mutated and constitutively active Ras. The molecular scaffolds Kinase Suppressor of Ras 1 and 2 (KSR1 and KSR2) play potent roles in promoting Ras-mediated signaling through the Raf/MEK/ERK kinase cascade. Here we summarize the canonical role of KSR in cells, including its central role as a scaffold protein for the Raf/MEK/ERK kinase cascade, its regulation of various cellular pathways mediated through different binding partners, and the phenotypic consequences of KSR1 or KSR2 genetic inactivation...
2017: F1000Research
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