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Nicolina E Savvaidou, Lazaros C Triarhou
Professor Emil Redlich (1866-1930) of the University of Vienna was born 150 years ago. Raised in a humble environment, he became an eminent researcher and neurology scholar, and succeeded in laying some of the key foundations of neuroanatomy and neuropathology. His name is linked to medical eponyms that define the dorsal root entry zone into the spinal cord, epidemic disseminated encephalomyelitis, narcolepsy, senile plaques and dementia. As its first director, he managed to organize the Maria-Theresien-Schlössel into a first-class neuropsychiatric hospital...
October 21, 2016: European Neurology
Yanfen Fang, Yannan Kong, Jianbei Xi, Mengli Zhu, Tong Zhu, Tongtong Jiang, Wenhao Hu, Mingliang Ma, Xiongwen Zhang
NEK2 is a conserved mitotic regulator critical for cell cycle progression. Aberrant expression of NEK2 has been found in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. In the present study, we have identified a novel compound MBM-5, which was found to bind to NEK2 with high affinity by docking simulations study. MBM-5 potently inhibited NEK2 kinase activity in vitro in a concentration-dependent manner. MBM-5 also suppressed cellular NEK2 kinase activity, as evidenced by the decreased phosphorylation of its substrate Hec1 on S165 in a concentration- and time-dependent manner...
October 15, 2016: Oncotarget
Kaijun Di, Naomi Lomeli, Spencer D Wood, Christopher D Vanderwal, Daniela A Bota
Mitochondrial dysfunction is a hallmark of cancer biology. Tumor mitochondrial metabolism is characterized by an abnormal ability to function in scarce oxygen conditions through glycolysis (the Warburg effect), and accumulation of mitochondrial DNA defects are present in both hereditary neoplasia and sporadic cancers. Mitochondrial Lon is a major regulator of mitochondrial metabolism and the mitochondrial response to free radical damage, and plays an essential role in the maintenance and repair of mitochondrial DNA...
October 15, 2016: Oncotarget
Zhenze Zhao, Xiuye Ma, Spencer D Shelton, Derek C Sung, Monica Li, Daniel Hernandez, Maggie Zhang, Michael D Losiewiz, Yidong Chen, Alexander Pertsemlidis, Xiaojie Yu, Yuanhang Liu, Liqin Du
MYCN amplification is the most common genetic alteration in neuroblastoma and plays a critical role in neuroblastoma tumorigenesis. MYCN regulates neuroblastoma cell differentiation, which is one of the mechanisms underlying its oncogenic function. We recently identified a group of differentiation-inducing microRNAs. Given the demonstrated inter-regulation between MYCN and microRNAs, we speculated that MYCN and the differentiation-inducing microRNAs might form an interaction network to control the differentiation of neuroblastoma cells...
October 15, 2016: Oncotarget
Tong Zhou, Luke Erber, Bing Liu, Yankun Gao, Hai-Bin Ruan, Yue Chen
Proline hydroxylation is a critical cellular mechanism regulating oxygen-response pathways in tumor initiation and progression. Yet, its substrate diversity and functions remain largely unknown. Here, we report a system-wide analysis to characterize proline hydroxylation substrates in cancer cells using an immunoaffinity-purification assisted proteomics strategy. We identified 562 sites from 272 proteins in HeLa cells. Bioinformatic analysis revealed that proline hydroxylation substrates are significantly enriched with mRNA processing and stress-response cellular pathways with canonical and diverse flanking sequence motifs...
October 13, 2016: Oncotarget
Li Bo, Huchuan Cui, Zhengxian Fang, Tao Qun, Caoyun Xia
Resistance to taxol represents a major obstacle for long-term remission in ovarian cancer. Transforming Growth Factor-β-Activated Kinase 1 (TAK1) is a critical component in immune response pathway. However, the role of TAK1 in the development of chemoresistance in ovarian cancer remains unknown. Here, we showed that in vitro, taxol-resistant cells expressed higher TAK1, and the ratio of p-TAK1/TAK1 positively associated with taxol resistance in ovarian cancer cells. Inactivation of TAK1 by inhibitor 5Z-7-oxozeaenol or gene knockdown sensitized taxol cytotoxicity in vitro, promoting cell apoptosis and mitosis arrest...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Leihong Zhao, Lining Yang, Hongjun Lin, Meijia Zhang, Haiying Yu, Bao-Qiang Liao, Fangyuan Wang, Xiaoling Zhou, Renjie Li
While the adsorptive fouling in membrane bioreactors (MBRs) is highly dependent of the surface morphology, little progress has been made on modeling biocake layer surface morphology. In this study, a novel method, which combined static light scattering method for fractal dimension (Df) measurement with fractal method represented by the modified two-variable Weierstrass-Mandelbrot function, was proposed to model biocake layer surface in a MBR. Characterization by atomic force microscopy showed that the biocake surface was stochastic, disorder, self-similarity, and with non-integer dimension, illustrating obvious fractal features...
October 13, 2016: Bioresource Technology
Kei Itagaki, Minoru Takebayashi, Chiyo Shibasaki, Naoto Kajitani, Hiromi Abe, Mami Okada-Tsuchioka, Shigeto Yamawaki
BACKGROUND: While electroconvulsive therapy (ECT) treatment for depression is highly effective, the high rate of relapse is a critical problem. The current study investigated factors associated with the risk of relapse in mood disorders in patients in which ECT was initially effective. METHOD: The records of 100 patients with mood disorders (61 unipolar depression, 39 bipolar depression) who received and responded to an acute ECT course were retrospectively reviewed...
October 11, 2016: Journal of Affective Disorders
Ioly Kotta-Loizou, Spyridon N Vasilopoulos, Robert H A Coutts, Stamatios Theocharis
Hu-antigen R (HuR) is an RNA-binding posttranscriptional regulator that belongs to the Hu/ELAV family. HuR expression levels are modulated by a variety of proteins, microRNAs, chemical compounds, or the microenvironment, and in turn, HuR affects mRNA stability and translation of various genes implicated in breast cancer formation, progression, metastasis, and treatment. The aim of the present review is to critically summarize the role of HuR in breast cancer development and its potential as a prognosticator and a therapeutic target...
October 17, 2016: Neoplasia: An International Journal for Oncology Research
Thomas J Younts, Hannah R Monday, Barna Dudok, Matthew E Klein, Bryen A Jordan, István Katona, Pablo E Castillo
Long-term changes of neurotransmitter release are critical for proper brain function. However, the molecular mechanisms underlying these changes are poorly understood. While protein synthesis is crucial for the consolidation of postsynaptic plasticity, whether and how protein synthesis regulates presynaptic plasticity in the mature mammalian brain remain unclear. Here, using paired whole-cell recordings in rodent hippocampal slices, we report that presynaptic protein synthesis is required for long-term, but not short-term, plasticity of GABA release from type 1 cannabinoid receptor (CB1)-expressing axons...
October 19, 2016: Neuron
Courtney Boen
Research links Black-White health disparities to racial differences in socioeconomic status (SES), but understanding of the role of SES in racial health gaps has been restricted by reliance on static measures of health and socioeconomic well-being that mask the dynamic quality of these processes and ignore the racialized nature of the SES-health connection. Utilizing twenty-three years of longitudinal data from the Panel Study of Income Dynamics (1984-2007), this study uses multilevel growth curve models to examine how multiple dimensions of socioeconomic well-being-including long-term economic history and differential returns to SES-contribute to the life course patterning of Black-White health disparities across two critical markers of well-being: body mass index (N = 9057) and self-rated health (N = 11,329)...
October 11, 2016: Social Science & Medicine
Bruno Cessac, Arnaud Le Ny, Eva Löcherbach
We initiate a mathematical analysis of hidden effects induced by binning spike trains of neurons. Assuming that the original spike train has been generated by a discrete Markov process, we show that binning generates a stochastic process that is no longer Markov but is instead a variable-length Markov chain (VLMC) with unbounded memory. We also show that the law of the binned raster is a Gibbs measure in the DLR (Dobrushin-Lanford-Ruelle) sense coined in mathematical statistical mechanics. This allows the derivation of several important consequences on statistical properties of binned spike trains...
October 20, 2016: Neural Computation
William Severa, Ojas Parekh, Conrad D James, James B Aimone
The dentate gyrus forms a critical link between the entorhinal cortex and CA3 by providing a sparse version of the signal. Concurrent with this increase in sparsity, a widely accepted theory suggests the dentate gyrus performs pattern separation-similar inputs yield decorrelated outputs. Although an active region of study and theory, few logically rigorous arguments detail the dentate gyrus's (DG) coding. We suggest a theoretically tractable, combinatorial model for this action. The model provides formal methods for a highly redundant, arbitrarily sparse, and decorrelated output signal...
October 20, 2016: Neural Computation
Indu Jose Thoompumkal, Krishnan Rehna, Kumaraswamy Anbarasu, Sundarasamy Mahalingam
Guanine nucleotide binding protein-like 3-like (GNL3L) is an evolutionarily conserved putative nucleolar GTPase belonging to the HSR1-MMR1 family. In the present study, using protein-protein interaction assays, we show that Leucine Zipper Down-regulated in Cancer-1 (LDOC1) is a novel interacting partner of GNL3L. Furthermore, our results reveal that ectopic expression of LDOC1 destabilizes endogenous GNL3L levels and down modulates GNL3L-induced cell proliferation, in contrast, the knockdown of LDOC1 potentiates cell proliferation upon GNL3L expression...
October 20, 2016: Cell Cycle
Jin Kyung Kim, Hye-Mi Lee, Ki-Sun Park, Dong-Min Shin, Tae Sung Kim, Yi Sak Kim, Hyun-Woo Suh, Soo Yeon Kim, In Soo Kim, Jin-Man Kim, Ji-Woong Son, Kyung Mok Sohn, Sung Soo Jung, Chaeuk Chung, Sang-Bae Han, Chul-Su Yang, Eun-Kyeong Jo
Autophagy is an important antimicrobial effector process that defends against Mycobacterium tuberculosis (Mtb), the human pathogen causing tuberculosis (TB). MicroRNAs (miRNAs), endogenous noncoding RNAs, are involved in various biological functions and act as post-transcriptional regulators to target mRNAs. The process by which miRNAs affect antibacterial autophagy and host defense mechanisms against Mtb infections in human monocytes and macrophages is largely uncharacterized. In this study, we show that Mtb significantly induces the expression of MIR144*/hsa-miR-144-5p, which targets the 3'-untranslated region of DRAM2 (DNA damage regulated autophagy modulator 2) in human monocytes and macrophages...
October 20, 2016: Autophagy
Barbara Fenesi, Chelsea Mackinnon, Lucia Cheng, Joseph A Kim, Bruce C Wainman
The use of two-dimensional (2D) images is consistently used to prepare anatomy students for handling real specimen. This study examined whether the quality of 2D images is a critical component in anatomy learning. The visual clarity and consistency of 2D anatomical images was systematically manipulated to produce low-quality and high-quality images of the human hand and human eye. On day 0, participants learned about each anatomical specimen from paper booklets using either low-quality or high-quality images, and then completed a comprehension test using either 2D images or three-dimensional (3D) cadaveric specimens...
October 20, 2016: Anatomical Sciences Education
Jawed Iqbal, Mairaj Ahmed Ansari, Binod Kumar, Dipanjan Dutta, Arunava Roy, Leela Chikoti, Gina Pisano, Sujoy Dutta, Shahrooz Vahedi, Mohanan Valiya Veettil, Bala Chandran
IFI16 (gamma-interferon-inducible protein 16), a predominantly nuclear protein involved in transcriptional regulation, also functions as an innate immune response DNA sensor and induces the IL-1β and antiviral type-1 interferon-β (IFN-β) cytokines. We have shown that IFI16, in association with BRCA1, functions as a sequence independent nuclear sensor of episomal dsDNA genomes of KSHV, EBV and HSV-1. Recognition of these herpesvirus genomes resulted in IFI16 acetylation, BRCA1-IFI16-ASC-procaspase-1 inflammasome formation, cytoplasmic translocation, and IL-1β generation...
October 2016: PLoS Pathogens
Ke Ren, Wei Zhang, Xiaoqing Chen, Yingyu Ma, Yue Dai, Yimei Fan, Yayi Hou, Ren Xiang Tan, Erguang Li
The human HSV-1 and -2 are common pathogens of human diseases. Both host and viral factors are involved in HSV lytic infection, although detailed mechanisms remain elusive. By screening a chemical library of epigenetic regulation, we identified bromodomain-containing protein 4 (BRD4) as a critical player in HSV infection. We show that treatment with pan BD domain inhibitor enhanced both HSV infection. Using JQ1 as a probe, we found that JQ1, a defined BD1 inhibitor, acts through BRD4 protein since knockdown of BRD4 expression ablated JQ1 effect on HSV infection...
October 2016: PLoS Pathogens
David M Bogner, Mark A Kaemingk, Melissa R Wuellner
Little is known about how hatch phenology (e.g., the start, peak, and duration of hatching) could influence subsequent recruitment of freshwater fishes into a population. We used two commonly sympatric fish species that exhibit different hatching phenologies to examine recruitment across multiple life stages. Nine yellow perch (Perca flavescens) and bluegill (Lepomis macrochirus) annual cohorts were sampled from 2004 through 2013 across larval, age-0, age-1, and age-2 life stages in a Nebraska (U.S.A.) Sandhill lake...
2016: PloS One
Lucas C Wheeler, Micah T Donor, James S Prell, Michael J Harms
The S100 proteins are a large family of signaling proteins that play critical roles in biology and disease. Many S100 proteins bind Zn2+, Cu2+, and/or Mn2+ as part of their biological functions; however, the evolutionary origins of binding remain obscure. One key question is whether divalent transition metal binding is ancestral, or instead arose independently on multiple lineages. To tackle this question, we combined phylogenetics with biophysical characterization of modern S100 proteins. We demonstrate an earlier origin for established S100 subfamilies than previously believed, and reveal that transition metal binding is widely distributed across the tree...
2016: PloS One
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