Read by QxMD icon Read


Marzieh Ezzaty Mirhashemi, Farzad Noubary, Susan Chapman-Bonofiglio, Saul Tzipori, Gordon S Huggins, Giovanni Widmer
BACKGROUND: Human cryptosporidiosis is caused primarily by two species of apicomplexan protozoa, Cryptosporidium parvum and C. hominis. In cultured cell monolayers, the parasite undergoes two generations of asexual multiplication (merogony). However, the proportion of parasites completing the life-cycle is low and insufficient to sustain continuous propagation. Due to the intracellular location of meronts and later life-cycle stages, oocyst and sporozoites are the only forms of the parasite that can readily be isolated...
March 12, 2018: Parasites & Vectors
Francesco Franchi, Fabiana Rollini, Jose Rivas Rios, Andrea Rivas, Malhar Agarwal, Megha Kureti, Deepa Nagaraju, Mustafa Wali, Zubair Shaikh, Maryuri Briceno, Ahmed Nawaz, Jae Youn Moon, Latonya Been, Siva Suryadevara, Daniel Soffer, Martin M Zenni, Theodore A Bass, Dominick J Angiolillo
BACKGROUND : Switching between different classes of P2Y12 inhibitors, including de-escalation from ticagrelor to clopidogrel, commonly occurs in clinical practice. However, the pharmacodynamic profiles of this strategy have been poorly explored. METHODS : This was a prospective, randomized, open-label study conducted in patients on maintenance dosing (MD) of aspirin (81 mg/d) and clopidogrel (75 mg/d). After a 7-day run-in with ticagrelor (180 mg loading dose [LD] followed by 90 mg twice daily MD), patients (n=80) were randomized into 1 of 4 groups: group A, clopidogrel 600 mg LD 24 hours after the last MD of ticagrelor (C-600 mg-24h); group B, clopidogrel 600 mg LD 12 hours after the last MD of ticagrelor (C-600 mg-12h); group C, clopidogrel 75 mg/d MD 24 hours after the last MD of ticagrelor (C-75 mg-24h); and group D, ticagrelor 90 mg twice daily MD (T-90 mg twice daily)...
March 11, 2018: Circulation
Yoko Maruyama, Satoko Ueno, Mitsuhiro Morita, Fumio Hayashi, Shohei Maekawa
Neurons have well-developed membrane microdomains called "rafts" that are recovered as a detergent-resistant membrane microdomain fraction (DRM). NAP-22 is one of the major protein components of neuronal DRM. In a previous study, we showed that DRM-derived NAP-22 binds ganglioside and the inhibitory effect of ganglioside to calcineurin (CaN), a neuron-enriched calmodulin-regulated phosphoprotein phosphatase. Considering the important roles of CaN in neurons, identification of other cellular regulators of CaN could be a good clue to understand the molecular background of neuronal function...
March 7, 2018: Neuroscience Letters
Zhulong Hu, Yuang Wang, Qiaopeng Tang, Xiaodan Yang, Yali Qin, Mingzhou Chen
Viral invasion triggers the activation of the host antiviral response. Besides the innate immune response, stress granules (SGs) also act as an additional defense response to combat viral replication. However, many viruses have evolved various strategies to suppress SG formation to facilitate their own replication. Here, we show that viral mRNAs derived from human parainfluenza virus type 3 (HPIV3) infection induce SG formation in an eIF2α phosphorylation- and PKR-dependent manner in which viral mRNAs are sequestered and viral replication is inhibited independent of the interferon signaling pathway...
March 8, 2018: PLoS Pathogens
Achim Dickmanns, Christopher P Zschiedrich, Johannes Arens, Iwan Parfentev, Jan Gundlach, Romina Hofele, Piotr Neumann, Henning Urlaub, Boris Görke, Ralf Ficner, Jorg Stulke
Utilization of energy-rich carbon sources such as glucose is fundamental to the evolutionary success of bacteria. Glucose can be catabolized via glycolysis for feeding the intermediary metabolism. The methylglyoxal synthase MgsA produces methylglyoxal from the glycolytic intermediate dihydroxyacetone phosphate. Methylglyoxal is toxic, requiring stringent regulation of MgsA activity. In the Gram-positive bacterium Bacillus subtilis , an interaction with the phosphoprotein Crh controls MgsA activity. In the absence of preferred carbon sources, Crh is present in the nonphosphorylated state and binds to and thereby inhibits MgsA...
March 7, 2018: Journal of Biological Chemistry
C Helten, D Naguib, L Dannenberg, M Pöhl, A Ayhan, T Hohlfeld, B Levkau, M Kelm, T Zeus, A Polzin
BACKGROUND: High on-treatment platelet reactivity (HTPR) to antiplatelet medication leads to ischemic events, while low on-treatment platelet reactivity (LTPR) increases bleeding risk. However, various trials failed to demonstrate superiority of tailored antiplatelet regimes (ARCTIC, ANTARCTIC, Trigger-PCI, GRAVITAS). TROPICAL-ACS was the first study that proved benefit of tailoring antiplatelet medication according to platelet function analyzing. A potential reason may be that different platelet function assays were used in these trials...
March 7, 2018: Journal of Thrombosis and Haemostasis: JTH
Xavier Carette, John Platig, David C Young, Michaela Helmel, Albert T Young, Zhe Wang, Lakshmi-Prasad Potluri, Cameron Stuver Moody, Jumei Zeng, Sladjana Prisic, Joseph N Paulson, Jan Muntel, Ashoka V R Madduri, Jorge Velarde, Jacob A Mayfield, Christopher Locher, Tiansheng Wang, John Quackenbush, Kyu Y Rhee, D Branch Moody, Hanno Steen, Robert N Husson
Tuberculosis is the leading killer among infectious diseases worldwide. Increasing multidrug resistance has prompted new approaches for tuberculosis drug development, including targeted inhibition of virulence determinants and of signaling cascades that control many downstream pathways. We used a multisystem approach to determine the effects of a potent small-molecule inhibitor of the essential Mycobacterium tuberculosis Ser/Thr protein kinases PknA and PknB. We observed differential levels of phosphorylation of many proteins and extensive changes in levels of gene expression, protein abundance, cell wall lipids, and intracellular metabolites...
March 6, 2018: MBio
Gyosuke Sakashita, Hitoshi Kiyoi, Tomoki Naoe, Takeshi Urano
Nucleophosmin (NPM1) is a multifunctional phosphoprotein which plays important roles in diverse biological processes. NPM1 can form homo- or hetero-oligomers through its N-terminal region, and bind DNA and RNA through its C-terminal region. However, the monomer-oligomer distribution of NPM1, and the extent of NPM1 binding and unbinding to RNA in living cells, are not fully understood. In this work, we analysed molecular complexes of NPM1 using size exclusion chromatography. We found that a substantial fraction of NPM1 behaves as an oligomer in HeLa cells...
March 5, 2018: Scientific Reports
Hebatullah Laban, Andreas Weigert, Joana Zink, Amro Elgheznawy, Christoph Schürmann, Lea Günther, Randa Abdel Malik, Sabrina Bothur, Susanne Wingert, Rolf Bremer, Michael A Rieger, Bernhard Brüne, Ralf P Brandes, Ingrid Fleming, Peter M Benz
In ischemic vascular diseases, leukocyte recruitment and polarization are crucial for revascularization and tissue repair. We investigated the role of vasodilator-stimulated phosphoprotein (VASP) in vascular repair. After hindlimb ischemia induction, blood flow recovery, angiogenesis, arteriogenesis, and leukocyte infiltration into ischemic muscles in VASP-/- mice were accelerated. VASP deficiency also elevated the polarization of the macrophages through increased signal transducer and activator of transcription (STAT) signaling, which augmented the release of chemokines, cytokines, and growth factors to promote leukocyte recruitment and vascular repair...
March 5, 2018: Journal of Cell Biology
Sirada Srihirun, Barbora Piknova, Nathawut Sibmooh, Alan N Schechter
Nitrite is recognized as a bioactive nitric oxide (NO) metabolite. We have shown that nitrite inhibits platelet activation and increases platelet cGMP levels in the presence of partially deoxygenated erythrocytes. In this study, we investigated the effect of nitrite on phosphorylation of vasodilator-stimulated phosphoprotein on residue serine 239 (P-VASPSer239), a marker of protein kinase G (PKG) activation, in human platelets. In platelet-rich plasma (PRP), nitrite itself had no effect on levels of P-VASPSer239 while DEANONOate increased P-VASPSer239...
2018: PloS One
Erxu Pi, Chengmin Zhu, Wei Fan, Yingying Huang, Liqun Qu, Yangyang Li, Qinyi Zhao, Feng Ding, Lijuan Qiu, Huizhong Wang, B W Poovaiah, Liqun Du
Salinity causes osmotic stress to crops and limits their productivity. To understand the mechanism underlying soybean salt tolerance, proteomics approach was used to identify phosphoproteins altered by NaCl treatment. Results revealed that 412 of the 4698 quantitatively analyzed phosphopeptides were significantly up-regulated upon salt treatment, including a phosphopeptide covering the serine 59 in the transcription factor GmMYB173. Our data showed that GmMYB173 is one of the three MYB proteins differentially phosphorylated upon salt treatment, and a substrate of the casein kinase-II...
March 1, 2018: Molecular & Cellular Proteomics: MCP
Raghuveera Kumar Goel, Marta Paczkowska, Juri Reimand, Scott Napper, Kiven Erique Lukong
SRMS (Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites), also known as PTK 70 (Protein tyrosine kinase 70), is a non-receptor tyrosine kinase that belongs to the BRK family of kinases (BFKs). To date less is known about the cellular role of SRMS primarily due to the unidentified substrates or signaling intermediates regulated by the kinase. In this study, we used phosphotyrosine antibody-based immunoaffinity purification in large-scale label-free quantitative phosphoproteomics to identify novel candidate substrates of SRMS...
March 1, 2018: Molecular & Cellular Proteomics: MCP
Jesse Lyons, Douglas K Brubaker, Phaedra C Ghazi, Katherine R Baldwin, Amanda Edwards, Myriam Boukhali, Samantha Dale Strasser, Lucia Suarez-Lopez, Yi-Jang Lin, Vijay Yajnik, Joseph L Kissil, Wilhelm Haas, Douglas A Lauffenburger, Kevin M Haigis
Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract that has limited treatment options. To gain insight into the pathogenesis of chronic colonic inflammation (colitis), we performed a multiomics analysis that integrated RNA microarray, total protein mass spectrometry (MS), and phosphoprotein MS measurements from a mouse model of the disease. Because we collected all three types of data from individual samples, we tracked information flow from RNA to protein to phosphoprotein and identified signaling molecules that were coordinately or discordantly regulated and pathways that had complex regulation in vivo...
February 27, 2018: Science Signaling
Yuehan Pang, Xin Zhou, Yaling Chen, Jinsong Bao
Protein phosphorylation plays important roles in regulation of various molecular events such as plant growth and seed development. However, its involvement in starch biosynthesisis less understood. Here, a comparative phosphoproteomic analysis of two indica rice cultivars during grain development was performed. A total of 2079 and 2434 phosphopeptides from 1273 and 1442 phosphoproteins were identified, covering 2441 and 2808 phosphosites in indica rice 9311 and Guangluai4 (GLA4), respectively. Comparative analysis identified 303 differentially phosphorylated peptides, and 120 and 258 specifically phosphorylated peptides in 9311 and GLA4, respectively...
February 27, 2018: Journal of Agricultural and Food Chemistry
Catherine D E Wilder, Nikoleta Pavlaki, Tutku Dursun, Paul Gyimah, Ellice Caldwell-Dunn, Antonella Ranieri, Hannah R Lewis, Michael J Curtis
BACKGROUND & PURPOSE: Antiarrhythmic β-blockers are used in patients at risk of myocardial ischaemia, but the survival benefit and mechanisms are unclear. We hypothesised that β-blockers do not prevent ventricular fibrillation (VF), but instead inhibit the ability of catecholamines to facilitate ischaemia-induced VF, limiting the scope of their usefulness. EXPERIMENTAL APPROACH: ECGs were analysed from ischaemic Langendorff-perfused rat hearts perfused with adrenoceptor antagonists and/or exogenous catecholamines (313 nM noradrenaline+75 nM adrenaline; CATs) in a blinded and randomised study...
February 23, 2018: British Journal of Pharmacology
Jaileene Pérez-Morales, Angel Núñez-Marrero, Pedro G Santiago-Cardona
The retinoblastoma protein (pRb) is an important tumor suppressor and cell cycle repressor. pRb is a phosphoprotein whose function is regulated primarily at the level of phosphorylation, and therefore, detecting pRb's phosphorylation status in human tissue samples can be clinically informative. Unfortunately, detection of phosphorylated pRb residues can be technically challenging, as these residues can often be weak antigens. In this chapter, we describe an enhanced sensitivity immunohistochemistry protocol for the staining of phosphorylated serine 249 in pRb, in human lung tumor samples...
2018: Methods in Molecular Biology
Pedro G Santiago-Cardona, Jaileene Pérez-Morales, Jonathan González-Flores
The retinoblastoma tumor suppressor protein (pRb) is a preeminent tumor suppressor that acts as a cell cycle repressor, specifically as an inhibitor of the G1-S transition of the cell cycle . pRb is a phosphoprotein whose function is repressed by extensive phosphorylation in several key residues, and therefore, pRb's phosphorylation status has become a surrogate for pRb activity. In particular, hyperphosphorylation of pRb has been associated with pathological states such as cancer, and therefore, assessing pRb's phosphorylation status is increasingly gaining diagnostic and prognostic value, may be used to inform therapeutic decisions, and is also an important tool for the cancer biologists seeking an understanding of the molecular etiology of cancer...
2018: Methods in Molecular Biology
Xuejing Yang, Bin Lu, Xueqin Sun, Cuijuan Han, Chunling Fu, Kailin Xu, Min Wang, Dengju Li, Zhichao Chen, Puneet Opal, Qiang Wen, John D Crispino, Qian-Fei Wang, Zan Huang
Deregulation of key regulators of histone modification is important in the initiation and progression of human leukemia. Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) participates in histone acetylation and its role in acute myeloid leukemia remains unclear. Here we observed significant upregulation of ANP32A in primary AML cells, which was essential for AML cell proliferation, survival, and colony formation. Integrative analysis of the genome-wide histone H3 acetylation and gene expression demonstrated that ANP32A deficiency reduced histone H3 acetylation, in accordance with changes in gene expression...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Ayswarya Ravi, Shengchun Guo, Beth Rasala, Miller Tran, Stephen Mayfield, Zivko L Nikolov
Correct folding and post-translational modifications are vital for therapeutic proteins to elicit their biological functions. Osteopontin (OPN), a bone regenerative protein present in a range of mammalian cells, is an acidic phosphoprotein with multiple potential phosphorylation sites. In this study, the ability of unicellular microalgae, Chlamydomonas reinhardtii , to produce phosphorylated recombinant OPN in its chloroplast is investigated. This study further explores the impact of phosphorylation and expression from a "plant-like" algae on separation of OPN...
February 16, 2018: International Journal of Molecular Sciences
Xiao Zhou, Gang Li, Anna Kaplan, Michael M Gaschler, Xiaoyan Zhang, Zhipeng Hou, Jiang Mali, Roseann Zott, Serge Cremers, Brent R Stockwell, Wenzhen Duan
Huntington's disease (HD) is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin (HTT) gene encoding an elongated polyglutamine tract within the N-terminal of the Huntingtin protein (Htt) and leads to Htt misfolding, aberrant protein aggregation, and progressive appearance of disease symptoms. Chronic activation of endoplasmic reticulum (ER) stress by mutant Htt (mHtt) results in cellular dysfunction and ultimately cell death. Protein disulfide isomerase (PDI) is a chaperone protein located in the ER...
February 16, 2018: Human Molecular Genetics
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"