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Fadia J A Gujam, Donald C McMillan, Joanne Edwards
The aim of the present study was to examine the relationship between tumour cell expression of total and phosphorylated STAT1 (ph-STAT1) and STAT3 (ph-STAT-3), components of tumour microenvironment and survival in patients with invasive ductal breast cancer.Immunohistochemical analysis of total and ph-STAT1, and STAT3 were performed on tissue microarray of 384 breast cancer specimens. Tumour cell expression of STAT1 and STAT3 at both cytoplasmic and nuclear locations were combined and identified as STAT1/STAT3 tumour cell expression...
October 18, 2016: Oncotarget
Judith Hagenbuchner, Martina Rupp, Christina Salvador, Bernhard Meister, Ursula Kiechl-Kohlendorfer, Thomas Müller, Kathrin Geiger, Consolato Sergi, Petra Obexer, Michael J Ausserlechner
Neuroblastoma is the most frequent, extracranial solid tumor in children with still poor prognosis in stage IV disease. In this study, we analyzed FOXO3-phosphorylation and cellular localization in tumor biopsies and determined the function of this homeostasis regulator in vitro and in vivo. FOXO3-phosphorylation at threonine-32 (T32) and nuclear localization in biopsies significantly correlated with stage IV disease. DNA-damaging drugs induced nuclear accumulation of FOXO3, which was associated with elevated T32-phosphorylation in stage IV-derived neuroblastoma cells, thereby reflecting the in situ results...
October 18, 2016: Oncotarget
Katharina Grundler, Raffaela Rotter, Sloane Tilley, Joachim Pircher, Thomas Czermak, Mustaf Yakac, Erik Gaitzsch, Steffen Massberg, Florian Krötz, Hae-Young Sohn, Ulrich Pohl, Hanna Mannell, Bjoern F Kraemer
INTRODUCTION: Platelets possess critical hemostatic functions in the system of thrombosis and hemostasis, which can be affected by a multitude of external factors. Previous research has shown that platelets have the capacity to synthesize proteins de novo and more recently a multicatalytic protein complex, the proteasome, has been discovered in platelets. Due to its vital function for cellular integrity, the proteasome has become a therapeutic target for anti-proliferative drug therapies in cancer...
October 13, 2016: Thrombosis Research
Liang Li, Jin-Yu Zhao, Hui-Xia Chen, Hui-Dong Ju, Meng An, Zhen Xu, Lu-Ping Zhang
The cinnamon flounder Pseudorhombus cinnamoneus is a frequently consumed marine fish in China. However, the occurrence of ascaridoid larvae in P. cinnamoneus remains unclear. In the present study, a total of 85 P. cinnamoneus caught from the Yellow Sea (off Shidao, 36°52'57″N, 122°26'42″E) in 2011, which is located between mainland China and the Korean Peninsula, was investigated for ascaridoid larval infection. Four ascaridoid larval types, including Anisakis type I of Berland (1961), Hysterothylacium type of Smith (1983), Hysterothylacium type HL of Guo et al...
October 14, 2016: International Journal of Food Microbiology
Kyung-Ha Lee, Peipei Zhang, Hong Joo Kim, Diana M Mitrea, Mohona Sarkar, Brian D Freibaum, Jaclyn Cika, Maura Coughlin, James Messing, Amandine Molliex, Brian A Maxwell, Nam Chul Kim, Jamshid Temirov, Jennifer Moore, Regina-Maria Kolaitis, Timothy I Shaw, Bing Bai, Junmin Peng, Richard W Kriwacki, J Paul Taylor
Expansion of a hexanucleotide repeat GGGGCC (G4C2) in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Transcripts carrying (G4C2) expansions undergo unconventional, non-ATG-dependent translation, generating toxic dipeptide repeat (DPR) proteins thought to contribute to disease. Here, we identify the interactome of all DPRs and find that arginine-containing DPRs, polyGly-Arg (GR) and polyPro-Arg (PR), interact with RNA-binding proteins and proteins with low complexity sequence domains (LCDs) that often mediate the assembly of membrane-less organelles...
October 20, 2016: Cell
Aindrila Chatterjee, Janine Seyfferth, Jacopo Lucci, Ralf Gilsbach, Sebastian Preissl, Lena Böttinger, Christoph U Mårtensson, Amol Panhale, Thomas Stehle, Oliver Kretz, Abdullah H Sahyoun, Sergiy Avilov, Stefan Eimer, Lutz Hein, Nikolaus Pfanner, Thomas Becker, Asifa Akhtar
A functional crosstalk between epigenetic regulators and metabolic control could provide a mechanism to adapt cellular responses to environmental cues. We report that the well-known nuclear MYST family acetyl transferase MOF and a subset of its non-specific lethal complex partners reside in mitochondria. MOF regulates oxidative phosphorylation by controlling expression of respiratory genes from both nuclear and mtDNA in aerobically respiring cells. MOF binds mtDNA, and this binding is dependent on KANSL3. The mitochondrial pool of MOF, but not a catalytically deficient mutant, rescues respiratory and mtDNA transcriptional defects triggered by the absence of MOF...
October 20, 2016: Cell
Chongsheng He, Simone Sidoli, Robert Warneford-Thomson, Deirdre C Tatomer, Jeremy E Wilusz, Benjamin A Garcia, Roberto Bonasio
Interactions between noncoding RNAs and chromatin proteins play important roles in gene regulation, but the molecular details of most of these interactions are unknown. Using protein-RNA photocrosslinking and mass spectrometry on embryonic stem cell nuclei, we identified and mapped, at peptide resolution, the RNA-binding regions in ∼800 known and previously unknown RNA-binding proteins, many of which are transcriptional regulators and chromatin modifiers. In addition to known RNA-binding motifs, we detected several protein domains previously unknown to function in RNA recognition, as well as non-annotated and/or disordered regions, suggesting that many functional protein-RNA contacts remain unexplored...
October 20, 2016: Molecular Cell
Jiang Yue, James F Griffith, Fan Xiao, Lin Shi, Defeng Wang, Jiayun Shen, Priscilla Wong, Edmund K Li, Martin Li, Tena K Li, Tracy Y Zhu, Vivian W Hung, Ling Qin, Lai-Shan Tam
Objective To compare the bone healing effects of denosumab and alendronate in female rheumatoid arthritis (RA) patients by high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods This is a post-hoc analysis of a randomized-controlled trial (NCT01770106). 40 patients were randomized in a 1:1 ratio to receive either subcutaneous denosumab (60mg) once or oral alendronate (70mg) weekly for 6 months. The size of individual bone erosions and the presence and extent of erosion-associated sclerosis (marginal osteosclerosis) were measured in the second metacarpal head of the non-dominant hand at baseline, 3 and 6 months...
October 21, 2016: Arthritis Care & Research
Michael Chalick, Oded Jacobi, Edward Pichinuk, Christian Garbar, Armand Bensussan, Alan Meeker, Ravit Ziv, Tania Zehavi, Nechama I Smorodinsky, John Hilkens, Franz-Georg Hanisch, Daniel B Rubinstein, Daniel H Wreschner
Translation of mRNA in alternate reading frames (ARF) is a naturally occurring process heretofore underappreciated as a generator of protein diversity. The MUC1 gene encodes MUC1-TM, a signal-transducing trans-membrane protein highly expressed in human malignancies. Here we show that an AUG codon downstream to the MUC1-TM initiation codon initiates an alternate reading frame thereby generating a novel protein, MUC1-ARF. MUC1-ARF, like its MUC1-TM 'parent' protein, contains a tandem repeat (VNTR) domain. However, the amino acid sequence of the MUC1-ARF tandem repeat as well as N- and C- sequences flanking it differ entirely from those of MUC1-TM...
2016: PloS One
E Levy, M Byrne, D J Coates, B M Macdonald, S McArthur, S van Leeuwen
The influence of geographic range on species persistence has long been of interest and there is a need for a better understanding of the genetic consequences for species with restricted distributions, particularly with the increasing rate of global species extinctions. However, the genetic effects of restricted range are often confounded by the impacts of population distribution. We compared chloroplast and nuclear genetic diversity and differentiation in two acacias, the restricted, patchily distributed Acacia atkinsiana and the widespread, semi-continuously distributed A...
2016: PloS One
Yong-Sik Bong, Shahin Assefnia, Therese Tuohy, Deborah W Neklason, Randall W Burt, Jaeil Ahn, Hao-Wen J Jiang, Stephen W Byers
Vitamin D is implicated in the etiology of cancers of the gastrointestinal tract, usually characterized by alteration in the APC/β-catenin/TCF tumor suppressor pathway. The vitamin D receptor (VDR) is also implicated in cardiovascular and skin diseases as well as in immunity. Activated VDR can indirectly alter β-catenin nuclear localization and directly suppress β-catenin/TCF mediated transcriptional activity. We treated VDR null mice with the carcinogen azoxymethane (AOM) and generated mice bearing a mutated APC (hypomorph) on a VDR null background (Apc1638N/+Vdr-/-)...
October 19, 2016: Oncotarget
Yun Liang, Xin He, Xian Li, Xuzhao Zhang, Xiaohong Zhang, Lei Zhang, Xi Qiu, Xiaoying Zhao, Rongzhen Xu
Multiple myeloma (MM) remains incurable despite the development and the use of new agents. In our studies, we found that 4-chlorbenzoyl berbamine (BBMD9), a novel synthetic derivative of berbamine, inhibited the proliferation of MM cells in dose- and time-dependent manners. Flow cytometric (FCM) analysis revealed that MM cells were arrested in the G1 phase and that apoptotic cells increased in a time-dependent manner. Moreover, the BBMD9 treatment downregulated IKKα and IKKβ, inhibited p-IκBα, and blocked p65 nuclear localization...
October 21, 2016: Cancer Investigation
M Barbagallo, A Musumarra, L Cosentino, E Maugeri, S Heinitz, A Mengoni, R Dressler, D Schumann, F Käppeler, N Colonna, P Finocchiaro, M Ayranov, L Damone, N Kivel, O Aberle, S Altstadt, J Andrzejewski, L Audouin, M Bacak, J Balibrea-Correa, S Barros, V Bécares, F Bečvář, C Beinrucker, E Berthoumieux, J Billowes, D Bosnar, M Brugger, M Caamaño, M Calviani, F Calviño, D Cano-Ott, R Cardella, A Casanovas, D M Castelluccio, F Cerutti, Y H Chen, E Chiaveri, G Cortés, M A Cortés-Giraldo, S Cristallo, M Diakaki, C Domingo-Pardo, E Dupont, I Duran, B Fernandez-Dominguez, A Ferrari, P Ferreira, W Furman, S Ganesan, A García-Rios, A Gawlik, T Glodariu, K Göbel, I F Gonçalves, E González-Romero, E Griesmayer, C Guerrero, F Gunsing, H Harada, T Heftrich, J Heyse, D G Jenkins, E Jericha, T Katabuchi, P Kavrigin, A Kimura, M Kokkoris, M Krtička, E Leal-Cidoncha, J Lerendegui, C Lederer, H Leeb, S Lo Meo, S J Lonsdale, R Losito, D Macina, J Marganiec, T Martínez, C Massimi, P Mastinu, M Mastromarco, A Mazzone, E Mendoza, P M Milazzo, F Mingrone, M Mirea, S Montesano, R Nolte, A Oprea, A Pappalardo, N Patronis, A Pavlik, J Perkowski, M Piscopo, A Plompen, I Porras, J Praena, J Quesada, K Rajeev, T Rauscher, R Reifarth, A Riego-Perez, P Rout, C Rubbia, J Ryan, M Sabate-Gilarte, A Saxena, P Schillebeeckx, S Schmidt, P Sedyshev, A G Smith, A Stamatopoulos, G Tagliente, J L Tain, A Tarifeño-Saldivia, L Tassan-Got, A Tsinganis, S Valenta, G Vannini, V Variale, P Vaz, A Ventura, V Vlachoudis, R Vlastou, J Vollaire, A Wallner, S Warren, M Weigand, C Weiß, C Wolf, P J Woods, T Wright, P Žugec
The energy-dependent cross section of the ^{7}Be(n,α)^{4}He reaction, of interest for the so-called cosmological lithium problem in big bang nucleosynthesis, has been measured for the first time from 10 meV to 10 keV neutron energy. The challenges posed by the short half-life of ^{7}Be and by the low reaction cross section have been overcome at n_TOF thanks to an unprecedented combination of the extremely high luminosity and good resolution of the neutron beam in the new experimental area (EAR2) of the n_TOF facility at CERN, the availability of a sufficient amount of chemically pure ^{7}Be, and a specifically designed experimental setup...
October 7, 2016: Physical Review Letters
Jie Yang, Markus Guehr, Xiaozhe Shen, Renkai Li, Theodore Vecchione, Ryan Coffee, Jeff Corbett, Alan Fry, Nick Hartmann, Carsten Hast, Kareem Hegazy, Keith Jobe, Igor Makasyuk, Joseph Robinson, Matthew S Robinson, Sharon Vetter, Stephen Weathersby, Charles Yoneda, Xijie Wang, Martin Centurion
Observing the motion of the nuclear wave packets during a molecular reaction, in both space and time, is crucial for understanding and controlling the outcome of photoinduced chemical reactions. We have imaged the motion of a vibrational wave packet in isolated iodine molecules using ultrafast electron diffraction with relativistic electrons. The time-varying interatomic distance was measured with a precision 0.07 Å and temporal resolution of 230 fs full width at half maximum. The method is not only sensitive to the position but also the shape of the nuclear wave packet...
October 7, 2016: Physical Review Letters
David A Mazziotti
A central challenge of physics is the computation of strongly correlated quantum systems. The past ten years have witnessed the development and application of the variational calculation of the two-electron reduced density matrix (2-RDM) without the wave function. In this Letter we present an orders-of-magnitude improvement in the accuracy of 2-RDM calculations without an increase in their computational cost. The advance is based on a low-rank, dual formulation of an important constraint on the 2-RDM, the T2 condition...
October 7, 2016: Physical Review Letters
Junki Yoshitake, Joji Nasu, Yukitoshi Motome
Experimental identification of quantum spin liquids remains a challenge, as the pristine nature is to be seen in asymptotically low temperatures. We here theoretically show that the precursor of quantum spin liquids appears in the spin dynamics in the paramagnetic state over a wide temperature range. Using the cluster dynamical mean-field theory and the continuous-time quantum Monte Carlo method, which are newly developed in the Majorana fermion representation, we calculate the dynamical spin structure factor, relaxation rate in nuclear magnetic resonance, and magnetic susceptibility for the honeycomb Kitaev model whose ground state is a canonical example of the quantum spin liquid...
October 7, 2016: Physical Review Letters
Lauren M Schiebelhut, Sarah S Abboud, Liza E Gómez Daglio, Holly F Swift, Michael N Dawson
The inclusion of next-generation sequencing technologies in population genetic and phylogenetic studies has elevated the need to balance time and cost of DNA extraction without compromising DNA quality. We tested eight extraction methods - ranging from low- to high-throughput techniques - and eight phyla: Annelida, Arthropoda, Cnidaria, Chordata, Echinodermata, Mollusca, Ochrophyta, and Porifera. We assessed DNA yield, purity, efficacy, and cost of each method. Extraction efficacy was quantified using the proportion of successful polymerase chain reaction (PCR) amplification of two molecular markers for metazoans (mitochondrial COI and nuclear Histone 3) and one for Ochrophyta (mitochondrial nad6) at four time points - 0...
October 21, 2016: Molecular Ecology Resources
Ana Lúcia Anversa Segatto, Claudia Elizabeth Thompson, Loreta Brandão Freitas
Developmental genes are believed to contribute to major changes during plant evolution, from infrageneric to higher levels. Due to their putative high sequence conservation, developmental genes are rarely used as molecular markers, and few studies including these sequences at low taxonomic levels exist. WUSCHEL-related homeobox genes (WOX) are transcription factors exclusively present in plants and are involved in developmental processes. In this study, we characterized the infrageneric genetic variation of Petunia WOX genes...
October 20, 2016: Genetics and Molecular Biology
Wei Huang, Jiyuan Wu, Huiqin Yang, Yin Xiong, Rui Jiang, Tianpen Cui, Duyun Ye
Abnormal features of the systemic lupus erythematosus (SLE)-derived neutrophils, promoted aberrant immune response, have inspired new studies of the induction of autoimmunity and the development of organ damage in SLE. In this study, we explore the effect of milk fat globule-EGF factor 8 (MFG-E8) on the aberrant nitrification features in pristane-induced lupus. SLE patients and mice with pristane-induced lupus develop autoantibodies associated with MFG-E8 overproduction. However, the deletion of MFG-E8 leads to uncontrolled early pulmonary and peritoneal inflammation and tissue damage in mice with pristane-induced lupus...
October 21, 2016: Cell Death and Differentiation
Ji Luo, Qingyang Liu, Kunihiko Morihiro, Alexander Deiters
Using small molecules to control the function of proteins in live cells with complete specificity is highly desirable, but challenging. Here we report a small-molecule switch that can be used to control protein activity. The approach uses a phosphine-mediated Staudinger reduction to activate protein function. Genetic encoding of an ortho-azidobenzyloxycarbonyl amino acid using a pyrrolysyl transfer RNA synthetase/tRNACUA pair in mammalian cells enables the site-specific introduction of a small-molecule-removable protecting group into the protein of interest...
November 2016: Nature Chemistry
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