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Lai Yee Leung, Ying Deng-Bryant, Katherine Cardiff, Megan Winter, Frank Tortella, Deborah Shear
BACKGROUND: Energy metabolic dysfunction is a key determinant of cellular damage following traumatic brain injury and may be worsened by additional insults. This study evaluated the acute/subacute effects of combined hypoxemia (HX) and hemorrhagic shock (HS) on cerebral interstitial levels of glucose, lactate, and pyruvate in a rat model of penetrating ballistic-like brain injury (PBBI). METHODS: Rats were randomly assigned into the sham control, PBBI, and combined injury (P + HH) groups...
November 2016: Journal of Trauma and Acute Care Surgery
Eliza Tsitoura, Athol U Wells, Kostantinos Karagiannis, Ismini Lasithiotaki, Eirini Vasarmidi, Eleni Bibaki, Chara Koutoulaki, Hiroe Sato, Demetrios A Spandidos, Nikolaos M Siafakas, George Sourvinos, Katerina M Antoniou
MicroRNA signatures of BAL cells and alveolar macrophages are currently lacking in IPF. Here we sought to investigate the expression of fibrosis-related microRNAs in the cellular component of the BAL in IPF. We thus focused on microRNAs previously associated with fibrosis (miR-29a, miR-29b, miR-29c, let-7d, and miR-21) and rapid IPF progression (miR-185, miR-210, miR-302c-3p miR-376c and miR-423-5p). Among the tested microRNAs miR-29a and miR-185 were found significantly downregulated in IPF while miR-302c-3p and miR-376c were not expressed by BAL cells...
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
Qiyong Jiang, Yimin Liu, Shijuan Zhang, Naikun Li, Gaoling Sun
MiRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers. Aberrant miRNA expression has been observed in human glioblastoma (GBM). The present study was to evaluate the expression and molecular mechanisms of COX-2 and miR-26b in human GBM tissues and GBM cell lines T98G, U87 and U251. In the present study, we found that expression of miR-26b was markedly downregulated in GBM cell lines and human GBM tissues, compared to matched non-tumor associated tissues...
October 17, 2016: Oncotarget
Na Li, Yunhuan Yan, Angke Zhang, Jiming Gao, Chong Zhang, Xue Wang, Gaopeng Hou, Gaiping Zhang, Jinbu Jia, En-Min Zhou, Shuqi Xiao
Many viruses encode microRNAs (miRNAs) that are small non-coding single-stranded RNAs which play critical roles in virus-host interactions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically impactful viruses in the swine industry. The present study sought to determine whether PRRSV encodes miRNAs that could regulate PRRSV replication. Four viral small RNAs (vsRNAs) were mapped to the stem-loop structures in the ORF1a, ORF1b and GP2a regions of the PRRSV genome by bioinformatics prediction and experimental verification...
October 17, 2016: Oncotarget
Sandeep Pallerla, Ted Gauthier, Rushikesh Sable, Seetharama D Jois
Doxorubicin (DOX) belongs to the anthracycline class of drugs that are used in the treatment of various cancers. It has limited cystostatic effects in therapeutic doses, but higher doses can cause cardiotoxicity. In the current approach, we conjugated a peptidomimetic (Arg-aminonaphthylpropionic acid-Phe, compound 5) known to bind to HER2 protein to DOX via a glutaric anhydride linker. Antiproliferative assays suggest that the DOX-peptidomimetic conjugate has activity in the lower micromolar range. The conjugate exhibited higher toxicity in HER2-overexpressed cells than in MCF-7 and MCF-10A cells that do not overexpress HER2 protein...
October 10, 2016: European Journal of Medicinal Chemistry
Jan Reckenbeil, Dominik Kraus, Helmut Stark, Birgit Rath-Deschner, Andreas Jäger, Matthias Wenghoefer, Jochen Winter, Werner Götz
OBJECTIVE: The objective of this study was to investigate effects of insulin-like growth factor 1 (IGF1) on proliferation, wound healing and differentiation processes of human periodontal ligament (PDL) cells under inflammatory conditions and whether the protective, anabolic effects of IGF1 can attenuate unfavorable effects of interleukin-1β (IL-1β). DESIGN: Inflammation was mimicked through cell stimulation with IL-1β. PDL cells were characterized in respect to the presence of components of the IGF system and the responsive potential on IL-1β incubation...
October 15, 2016: Archives of Oral Biology
Jasmine Rae Frost, Oladunni Olanubi, Stephen Ka-Hon Cheng, Andrea Soriano, Leandro Crisostomo, Alennie Lopez, Peter Pelka
Human adenovirus infects terminally differentiated cells and to replicate it must induce S-phase. The chief architects that drive adenovirus-infected cells into S-phase are the E1A proteins, with 5 different isoforms expressed during infection. E1A remodels the infected cell by associating with cellular factors and modulating their activity. The C-terminus of E1A is known to bind to only a handful of proteins. We have identified a novel E1A C-terminus binding protein, Ku70 (XRCC6), which was found to bind directly within the CR4 of E1A from human adenovirus type 5...
October 18, 2016: Virology
E Kamanga-Sollo, K J Thornton, M E White, W R Dayton
In feedlot steers, estradiol-17β (E2) and combined E2 and trenbolone acetate (a testosterone analog) implants enhance rate and efficiency of muscle growth; and, consequently, these compounds are widely used as growth promoters in several countries. Treatment with E2 stimulates protein synthesis rate and suppresses protein degradation rate in fused bovine satellite cell (BSC) cultures; however, the mechanisms involved in these effects are not known with certainty. Although the genomic effects of E2 mediated through the classical estrogen receptors have been characterized, recent studies indicate that binding of E2 to the G protein-coupled estrogen receptor (GPER)-1 mediates nongenomic effects of E2 on cellular function...
September 13, 2016: Domestic Animal Endocrinology
Malik Nassan, Qingqin Li, Paul E Croarkin, Wenan Chen, Colin L Colby, Marin Veldic, Susan L McElroy, Gregory D Jenkins, Euijung Ryu, Julie M Cunningham, Marion Leboyer, Mark A Frye, Joanna M Biernacka
BACKGROUND: Although multiple genes have been implicated in bipolar disorder (BD), they explain only a small proportion of its heritability. Identifying additional BD risk variants may be impaired by phenotypic heterogeneity, which is usually not taken into account in genome-wide association studies (GWAS). BD with early age at onset is a more homogeneous familial form of the disorder associated with greater symptom severity. METHODS: We conducted a GWAS of early-onset BD (onset of mania/hypomania ≤19 years old) in a discovery sample of 419 cases and 1034 controls and a replication sample of 181 cases and 777 controls...
September 30, 2016: Journal of Affective Disorders
Giulia Suarato, Seong-Il Lee, Weiyi Li, Sneha Rao, Tanvir Khan, Yizhi Meng, Maya Shelly
During mammalian embryonic development, neurons polarize to create distinct cellular compartments of axon and dendrite that inherently differ in form and function, providing the foundation for directional signaling in the nervous system. Polarization results from spatio-temporal segregation of specific proteins' activities to discrete regions of the neuron to dictate axonal vs. dendritic fate. We aim to manipulate axon formation by directed subcellular localization of crucial intracellular protein function...
October 8, 2016: Biomaterials
Julien Muffat, Yun Li, Rudolf Jaenisch
In vitro differentiation of human pluripotent stem cells provides a systematic platform to investigate the physiological development and function of the human nervous system, as well as the etiology and consequence when these processes go awry. Recent development in three-dimensional (3D) organotypic culture systems allows modeling of the complex structure formation of the human CNS, and the intricate interactions between various resident neuronal and glial cell types. Combined with an ever-expanding genome editing and regulation toolkit such as CRISPR/Cas9, it is now a possibility to study human neurological disease in the relevant molecular, cellular and anatomical context...
October 18, 2016: Current Opinion in Cell Biology
Stacy-Anne Morgan, Dana C Nadler, Rayka Yokoo, David F Savage
Metabolic engineering offers the potential to renewably produce important classes of chemicals, particularly biofuels, at an industrial scale. DNA synthesis and editing techniques can generate large pathway libraries, yet identifying the best variants is slow and cumbersome. Traditionally, analytical methods like chromatography and mass spectrometry have been used to evaluate pathway variants, but such techniques cannot be performed with high throughput. Biosensors - genetically encoded components that actuate a cellular output in response to a change in metabolite concentration - are therefore a promising tool for rapid and high-throughput evaluation of candidate pathway variants...
October 18, 2016: Current Opinion in Chemical Biology
Isabel P G Fernandes, Ana Maria Oliveira-Brett
Calmodulin (CaM) is an essential protein present in all eukaryote cells, ranging from vertebrates to unicellular organisms. CaM is the most important Ca(2+) signalling protein, composed of two domains, N- and C-terminal domains, linked by a flexible central α-helix, and is responsible for the regulation of numerous calcium-mediated signalling pathways. Four calcium ions bind to CaM, changing its conformation and determining how it recognizes and regulates its cellular targets. The oxidation mechanism of native and denatured CaM, at a glassy carbon electrode, was investigated using differential pulse voltammetry and electrochemical impedance spectroscopy...
October 7, 2016: Bioelectrochemistry
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
Cong Wu, Meng-Qing Gong, Bo-Ya Liu, Ren-Xi Zhuo, Si-Xue Cheng
To effectively reverse multiple drug resistance (MDR) in tumor treatments, a functional nano-sized drug delivery system with active targeting function and pH sensitivity was prepared for the co-delivery of multiple drug resistance inhibitors. Buthionine sulfoximine (BSO) to inhibit GSH synthesis and celecoxib (CXB) to down-regulate P-gp expression were co-loaded in polymer/inorganic hybrid nanoparticles to form buthionine sulfoximine/celecoxib@biotin-heparin/heparin/calcium carbonate/calcium phosphate nanoparticles (BSO/CXB@BNP)...
October 13, 2016: Colloids and Surfaces. B, Biointerfaces
Laura de Diego-García, Mercedes Ramírez-Escudero, Álvaro Sebastián-Serrano, Juan Ignacio Diaz-Hernández, Jesús Pintor Just, José J Lucas, Miguel Díaz-Hernández
The Ubiquitin-Proteasome System (UPS) is essential for the regulation of the cellular proteostasis. Indeed, it has been postulated that an UPS dysregulation is the common mechanism that underlies several neurological disorders. Considering that extracellular nucleotides, through their selective P2Y2 receptor (P2Y2R), play a neuroprotective role in various neurological disorders that course with an UPS impairment, we wonder if this neuroprotective capacity resulted from their ability to modulate the UPS. Using a cellular model expressing two different UPS reporters, we found that the stimulation of P2Y2R by its selective agonist Up4U induced a significant reduction of UPS reporter levels...
October 18, 2016: Biochimica et Biophysica Acta
Yi Lin, Eiichiro Mori, Masato Kato, Siheng Xiang, Leeju Wu, Ilmin Kwon, Steven L McKnight
Two complementary approaches were used in search of the intracellular targets of the toxic PR poly-dipeptide encoded by the repeat sequences expanded in the C9orf72 form of amyotrophic lateral sclerosis. The top categories of PRn-bound proteins include constituents of non-membrane invested cellular organelles and intermediate filaments. PRn targets are enriched for the inclusion of low complexity (LC) sequences. Evidence is presented indicating that LC sequences represent the direct target of PRn binding and that interaction between the PRn poly-dipeptide and LC domains is polymer-dependent...
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
Jorge Moscat, Michael Karin, Maria T Diaz-Meco
Adaptor proteins participate in selective autophagy, which is critical for cellular detoxification and stress relief. However, new evidence supports an autophagy-independent key role of the adaptor p62 (encoded by the gene Sqstm1) in signaling functions central to tumor initiation in the epithelium and suppression of tumor progression in the stroma.
October 20, 2016: Cell
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