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Michael L Schulte, Matthew R Hight, Gregory D Ayers, Qi Liu, Yu Shyr, M Kay Washington, H Charles Manning
PURPOSE: This study aimed to study whether cancer cells possess distinguishing metabolic features compared with surrounding normal cells, such as increased glutamine uptake. Given this, quantitative measures of glutamine uptake may reflect critical processes in oncology. Approximately, 10 % of patients with colorectal cancer (CRC) express BRAF (V600E) , which may be actionable with selective BRAF inhibitors or in combination with inhibitors of complementary signaling axes. Non-invasive and quantitative predictive measures of response to these targeted therapies remain poorly developed in this setting...
October 21, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Akhi Akhter, Emanuel Rosonina
The Saccharomyces cerevisiae transcription factor Gcn4 is expressed during amino acid starvation and its abundance is controlled by ubiquitin-mediated proteolysis. Cdk8, a kinase component of the RNA polymerase II Mediator complex, phosphorylates Gcn4 which triggers its ubiquitination/proteolysis and is thought to link Gcn4 degradation with transcription of target genes. In addition to phosphorylation and ubiquitination, we previously showed that Gcn4 becomes sumoylated in a DNA-binding dependent manner, while a non-sumoylatable form of Gcn4 showed increased chromatin occupancy, but only if Cdk8 was present...
October 21, 2016: Genetics
Zhigang Sui, Yejing Weng, Qun Zhao, Nan Deng, Fei Fang, Xudong Zhu, Yichu Shan, Lihua Zhang, Yukui Zhang
The cartilage zone of the velvet antler is richly vascularized, this being a major difference to the classical cartilage, in which there are no blood vessels. Angiogenesis and rapid growth of vasculature in velvet antler cartilage (VAC) make it an ideal model for discovering the novel angiogenic regulatory factors. However, the proteomic analysis of VAC is challenging due to the serious interference of proteoglycans (PGs) and collagens. To achieve a comprehensive proteome characterization of VAC, herein, we developed an ionic liquid-based method using 1-dodecyl-3-methylimidazolium chloride ([C12-mim]Cl) for selective extraction of cellular proteins from VAC...
December 1, 2016: Talanta
Elena Hernandez-Encinas, Diana Aguilar-Morante, Jose A Morales-Garcia, Elena Gine, Marina Sanz-SanCristobal, Angel Santos, Ana Perez-Castillo
BACKGROUND: The CCAAT/enhancer-binding protein β (C/EBPβ) is a transcription factor implicated in the control of proliferation, differentiation, and inflammatory processes mainly in adipose tissue and liver; although more recent results have revealed an important role for this transcription factor in the brain. Previous studies from our laboratory indicated that CCAAT/enhancer-binding protein β is implicated in inflammatory process and brain injury, since mice lacking this gene were less susceptible to kainic acid-induced injury...
October 21, 2016: Journal of Neuroinflammation
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
Ruben Perez-Carrasco, Pilar Guerrero, James Briscoe, Karen M Page
During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules-morphogens-guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms...
October 2016: PLoS Computational Biology
Christine M Freeman, Jeffrey L Curtis
Hallmarks of chronic obstructive pulmonary disease (COPD) include innate inflammation and remodeling of small airways that begin in early disease and the development of lung lymphoid follicles (LLF), indicative of adaptive immunity, in more spirometrically-severe stages. Common to these processes in all stages is orchestration by dendritic cells (DC). Recently improved understanding of the analogous lung DC subsets in humans and mice has allowed for better integration and interpretation of the experimental and clinical pathological literature...
October 21, 2016: American Journal of Respiratory Cell and Molecular Biology
Hugo Pereira, Katkam N Gangadhar, Peter S C Schulze, Tamára Santos, Carolina Bruno de Sousa, Lisa M Schueler, Luísa Custódio, F Xavier Malcata, Luísa Gouveia, João C S Varela, Luísa Barreira
Bioprospecting for novel microalgal strains is key to improving the feasibility of microalgae-derived biodiesel production. Tetraselmis sp. CTP4 (Chlorophyta, Chlorodendrophyceae) was isolated using fluorescence activated cell sorting (FACS) in order to screen novel lipid-rich microalgae. CTP4 is a robust, euryhaline strain able to grow in seawater growth medium as well as in non-sterile urban wastewater. Because of its large cell size (9-22 μm), CTP4 settles down after a six-hour sedimentation step. This leads to a medium removal efficiency of 80%, allowing a significant decrease of biomass dewatering costs...
October 21, 2016: Scientific Reports
Inimary T Toby, Mikhail K Levin, Edward A Salinas, Scott Christley, Sanchita Bhattacharya, Felix Breden, Adam Buntzman, Brian Corrie, John Fonner, Namita T Gupta, Uri Hershberg, Nishanth Marthandan, Aaron Rosenfeld, William Rounds, Florian Rubelt, Walter Scarborough, Jamie K Scott, Mohamed Uduman, Jason A Vander Heiden, Richard H Scheuermann, Nancy Monson, Steven H Kleinstein, Lindsay G Cowell
BACKGROUND: The genes that produce antibodies and the immune receptors expressed on lymphocytes are not germline encoded; rather, they are somatically generated in each developing lymphocyte by a process called V(D)J recombination, which assembles specific, independent gene segments into mature composite genes. The full set of composite genes in an individual at a single point in time is referred to as the immune repertoire. V(D)J recombination is the distinguishing feature of adaptive immunity and enables effective immune responses against an essentially infinite array of antigens...
October 6, 2016: BMC Bioinformatics
Damarius S Fleming, Laura C Miller
Eight RNA samples taken from the tracheobronchial lymph nodes (TBLN) of pigs that were either infected or non-infected with a feral isolate of porcine pseudorabies virus (PRV) were used to investigate changes in gene expression related to the pathogen. The RNA was processed into fastq files for each library prior to being analyzed using Illumina Digital Gene Expression Tag Profiling sequences (DGETP) which were used as the downstream measure of differential expression. Analyzed tags consisted of 21 base pair sequences taken from time points 1, 3, 6, and 14 days' post infection (dpi) that generated 1,927,547 unique tag sequences...
December 2016: Genomics Data
Teresa Delgado-Goni, Maria Falck Miniotis, Slawomir Wantuch, Harold G Parkes, Richard Marais, Paul Workman, Martin O Leach, Mounia Beloueche-Babari
Understanding the impact of BRAF signaling inhibition in human melanoma on key disease mechanisms is important for developing biomarkers of therapeutic response and combination strategies to improve long term disease control. This work investigates the downstream metabolic consequences of BRAF inhibition with vemurafenib, the molecular and biochemical processes that underpin them, their significance for antineoplastic activity and potential as non-invasive imaging response biomarkers.(1)H NMR spectroscopy showed that vemurafenib decreases the glycolytic activity of BRAF mutant (WM266...
October 7, 2016: Molecular Cancer Therapeutics
Katrin Ochsenreither, Claudia Glück, Timo Stressler, Lutz Fischer, Christoph Syldatk
Polyunsaturated fatty acids (PUFAs) of the ω-3 and ω-6 class (e.g., α-linolenic acid, linoleic acid) are essential for maintaining biofunctions in mammalians like humans. Due to the fact that humans cannot synthesize these essential fatty acids, they must be taken up from different food sources. Classical sources for these fatty acids are porcine liver and fish oil. However, microbial lipids or single cell oils, produced by oleaginous microorganisms such as algae, fungi and bacteria, are a promising source as well...
2016: Frontiers in Microbiology
Meng Wu, Lishann Ingram, Ezequiel J Tolosa, Renzo E Vera, Qianjin Li, Sungjin Kim, Yongjie Ma, Demetri D Spyropoulos, Zanna Beharry, Jiaoti Huang, Martin E Fernandez-Zapico, Houjian Cai
Although the differentiation of oncogenically transformed basal progenitor cells is one of the key steps in prostate tumorigenesis, the mechanisms mediating this cellular process are still largely unknown. Here we demonstrated that an expanded p63+ and CK5+ basal/progenitor cell population, induced by the concomitant activation of oncogenic Kras(G12D) and androgen receptor (AR) signaling, underwent cell differentiation in vivo. The differentiation process led to suppression of the p63 expressing cells with a decreased number of CK5+ basal cells, but an increase of CK8+ luminal tumorigenic cells, and revealed a hierarchal lineage pattern consisting of p63+/CK5+ progenitor, CK5+/CK8+ transitional progenitor, and CK8+ differentiated luminal cells...
October 19, 2016: Journal of Biological Chemistry
Daniel Hachim, Samuel T LoPresti, Cecelia C Yates, Bryan N Brown
The present study tests the hypothesis that transient, early-stage shifts in macrophage polarization at the tissue-implant interface from a pro-inflammatory (M1) to an anti-inflammatory/regulatory (M2) phenotype mitigates the host inflammatory reaction against a non-degradable polypropylene mesh material and improves implant integration downstream. To address this hypothesis, a nanometer-thickness coating capable of releasing IL-4 (an M2 polarizing cytokine) from an implant surface at early stages of the host response has been developed...
October 11, 2016: Biomaterials
Jonatan Enk, Assi Levi, Yiska Weisblum, Rachel Yamin, Yoav Charpak-Amikam, Dana G Wolf, Ofer Mandelboim
Herpes simplex virus 1 (HSV1) is a ubiquitous human pathogen that utilizes variable mechanisms to evade immune surveillance. The glycosylphosphatidylinositol (GPI) anchoring pathway is a multistep process in which a myriad of different proteins are covalently attached to a GPI moiety to be presented on the cell surface. Among the different GPI-anchored proteins there are many with immunological importance. We present evidence that the HSV1-encoded miR H8 directly targets PIGT, a member of the protein complex that covalently attaches proteins to GPI in the final step of GPI anchoring...
October 18, 2016: Cell Reports
Xiao-Qian Li, Zai-Li Zhang, Wen-Fei Tan, Xi-Jia Sun, Hong Ma
Toll-like receptor 4 (TLR4) is important for the pathogenesis of inflammatory reactions and the promotion of pain processing after ischemia/reperfusion (IR) in spinal cord. Recently, C-X-C chemokine ligand 12 (CXCL12) and its receptor, C-X-C chemokine receptor 4 (CXCR4), were demonstrated to be simultaneously critical for inflammatory reactions, thereby facilitating glial activation. However, whether CXCL12/CXCR4 expression can contribute to IR-induced inflammatory pain via spinal TLR4 remained unclear. A rat model was established by 8 min of aortic arch occlusion...
2016: PloS One
S P Pfeifer
Sequencing has revolutionized biology by permitting the analysis of genomic variation at an unprecedented resolution. High-throughput sequencing is fast and inexpensive, making it accessible for a wide range of research topics. However, the produced data contain subtle but complex types of errors, biases and uncertainties that impose several statistical and computational challenges to the reliable detection of variants. To tap the full potential of high-throughput sequencing, a thorough understanding of the data produced as well as the available methodologies is required...
October 19, 2016: Heredity
Wayne O Miles, Antonio Lembo, Angela Volorio, Elena Brachtel, Bin Tian, Dennis Sgroi, Paolo Provero, Nicholas Dyson
Alternative polyadenylation (APA) is a process that changes the post-transcriptional regulation and translation potential of mRNAs via addition or deletion of 3'UTR sequences. To identify post-transcriptional regulatory events affected by APA in breast tumors, tumor datasets were analyzed for recurrent APA events. Motif mapping of the changed 3'UTR region found that APA-mediated removal of Pumilio Regulatory Elements (PRE) was unusually common. Breast tumor sub-type specific APA profiling identified triple-negative breast tumors as having the highest levels of APA...
October 10, 2016: Cancer Research
Janghyun Yoo, Tae-Sun Lee, Byungsan Choi, Min Ju Shon, Tae-Young Yoon
Extremely weak protein-protein interactions (PPIs), signified by micromolar or even millimolar dissociation constants, are one of the keys to understanding the rapid responses of cellular systems. Although single-molecule methods are particularly useful in determining kinetics of biological processes, their application is largely limited to rather strong interactions because of the diffraction-limited observation volume. In this study, we report a single-molecule method that allows the characterization of PPIs using a prey concentration four orders of magnitude lower than the dissociation constant...
October 19, 2016: Journal of the American Chemical Society
Carlos Vera, Andrés Córdova, Carla Aburto, Cecilia Guerrero, Sebastián Suárez, Andrés Illanes
Lactose-derived non-digestible oligosaccharides are prominent components of functional foods. Among them, galacto-oligosaccharides (GOS) outstand for being prebiotics whose health-promoting effects are supported on strong scientific evidences, having unique properties as substitutes of human milk oligosaccharides in formulas for newborns and infants. GOS are currently produced enzymatically in a kinetically-controlled reaction of lactose transgalactosylation catalyzed by β-galactosidases from different microbial strains...
December 2016: World Journal of Microbiology & Biotechnology
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