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Zhisong He, Qianhui Yu
BACKGROUND: Neuron maturation is a critical process in neurogenesis, during which neurons gain their morphological, electrophysiological and molecular characteristics for their functions as the central components of the nervous system. RESULTS: To better understand the molecular changes during this process, we combined the protein-protein interaction network and public single cell RNA-seq data of mature and immature neurons to identify functional modules relevant to the neuron maturation process in humans...
April 17, 2018: BMC Genomics
Pathima Nusrath Hameed, Karin Verspoor, Snezana Kusljic, Saman Halgamuge
BACKGROUND: Drug repositioning is the process of identifying new uses for existing drugs. Computational drug repositioning methods can reduce the time, costs and risks of drug development by automating the analysis of the relationships in pharmacology networks. Pharmacology networks are large and heterogeneous. Clustering drugs into small groups can simplify large pharmacology networks, these subgroups can also be used as a starting point for repositioning drugs. In this paper, we propose a two-tiered drug-centric unsupervised clustering approach for drug repositioning, integrating heterogeneous drug data profiles: drug-chemical, drug-disease, drug-gene, drug-protein and drug-side effect relationships...
April 11, 2018: BMC Bioinformatics
Xiaojing Huang, Hongwen Zhu, Zemin Gao, Junzun Li, Junlong Zhuang, Yu Dong, Bing Shen, Meiqian Li, Hu Zhou, Hongqian Guo, Ruimin Huang, Jun Yan
Once urinary bladder cancer (UBC) develops into muscle-invasive bladder cancer, its mortality rate increases dramatically. However, the molecular mechanisms of UBC invasion and metastasis remain largely unknown. Herein, using 5637 UBC cells, we generated two sublines with low (5637 NMI) and high (5637 HMI) invasive capabilities. Mass spectrum analyses revealed that the Wnt family protein Wnt7a is more highly expressed in 5637 HMI cells than in 5637 NMI cells. We also found that increased Wnt7a expression is associated with UBC metastasis and predicted worse clinical outcome in UBC patients...
March 16, 2018: Journal of Biological Chemistry
Prakash Chandra, Alain M Jonas, Antony E Fernandes
Confinement and cooperativity are important design principles used by Nature to optimize catalytic activity in enzymes. In these biological systems, the precise sequence of the protein encodes for specific chain folding to preorganize critical amino acid side chains within defined binding pockets, allowing to express and trigger synergistic catalytic activation pathways. Here we show that short synthetic precision oligomers with the optimal sequence of catalytic units, spatially arranged by dense surface grafting to form confined cooperative "pockets", display an up to 5-fold activity improvement compared to a "mismatched" sequence or free oligomers using the (pyta)Cu/TEMPO/NMI-catalyzed aerobic selective oxidation of alcohols as a model reaction...
March 15, 2018: Journal of the American Chemical Society
Kathrin Breuer, Cord B Meyer, Felix A Breuer, Anne Richter, Florian Exner, Andreas Max Weng, Serge Stroehle, Bülent Polat, Peter M Jakob, Otto A Sauer, Michael Flentje, Stefan Weick
The purpose of this work is the development of a robust and reliable three-dimensional (3D) Cartesian imaging technique for fast and flexible retrospective four-dimensional abdominal MRI during free breathing. To this end, a non-uniform quasi random (NU-QR) reordering of the phase encoding (ky-kz) lines was incorporated into three-dimensional Cartesian acquisition. The proposed sampling scheme allocates more phase encoding points near the k-space origin while reducing the sampling density in the outer part of the k-space...
March 1, 2018: Physics in Medicine and Biology
Kyle R Padgett, Radka Stoyanova, Sara Pirozzi, Perry Johnson, Jon Piper, Nesrin Dogan, Alan Pollack
PURPOSE: Validating deformable multimodality image registrations is challenging due to intrinsic differences in signal characteristics and their spatial intensity distributions. Evaluating multimodality registrations using these spatial intensity distributions is also complicated by the fact that these metrics are often employed in the registration optimization process. This work evaluates rigid and deformable image registrations of the prostate in between diagnostic-MRI and radiation treatment planning-CT by utilizing a planning-MRI after fiducial marker placement as a surrogate...
February 23, 2018: Journal of Applied Clinical Medical Physics
Evgeny N Suspitsin, Grigoriy A Yanus, Marina Yu Dorofeeva, Tatiana A Ledashcheva, Nataliya V Nikitina, Galina V Buyanova, Elena V Saifullina, Anna P Sokolenko, Evgeny N Imyanitov
Tuberous sclerosis (TS) is a rare autosomal-dominant genetic disease. TS is manifested by the development of multiple hamartomas, which affect brain, kidneys, retina, skin and other organs. This study aimed to reveal specific features of molecular epidemiology of TS in Russia. Blood DNA samples from 61 patients with definite (n = 53) or probable (n = 8) clinical diagnosis of TS were tested for mutations in TSC1 and TSC2 genes using Sanger sequencing and MLPA analysis. Five TSC1/2 mutation-negative patients were further analyzed by exome sequencing...
February 23, 2018: Journal of Human Genetics
Angela Peron, Aglaia Vignoli, Francesca La Briola, Emanuela Morenghi, Lucia Tansini, Rosa Maria Alfano, Gaetano Bulfamante, Silvia Terraneo, Filippo Ghelma, Giuseppe Banderali, David H Viskochil, John C Carey, Maria Paola Canevini
Tuberous Sclerosis Complex (TSC) is a multisystemic condition caused by mutations in TSC1 or TSC2, but a pathogenic variant is not identified in up to 10% of the patients. The aim of this study was to delineate the phenotype of pediatric and adult patients with a definite clinical diagnosis of TSC and no mutation identified in TSC1 or TSC2. We collected molecular and clinical data of 240 patients with TSC, assessing over 50 variables. We compared the phenotype of the homogeneous group of individuals with No Mutation Identified (NMI) with that of TSC patients with a TSC1 and TSC2 pathogenic variant...
February 9, 2018: European Journal of Medical Genetics
Linyuan Feng, Jingxue Sheng, Gia-Phong Vu, Yujun Liu, Chingman Foo, Songbin Wu, Phong Trang, Marco Paliza-Carre, Yanhong Ran, Xiaoping Yang, Xu Sun, Zemin Deng, Tianhong Zhou, Sangwei Lu, Hongjian Li, Fenyong Liu
Interferon-γ (IFN-γ) represents one of the most important innate immunity responses in a host to combat infections of many human viruses including human herpesviruses. Human N-myc interactor (Nmi) protein, which has been shown to interact with signal transducer and activator of transcription (STAT) proteins including STAT1, is important for the activation of IFN-γ induced STAT1-dependent transcription of many genes responsible for IFN-γ immune responses. However, no proteins encoded by herpesviruses have been reported to interact with Nmi and inhibit Nmi-mediated activation of IFN-γ immune responses to achieve immune evasion from IFN-γ responses...
January 29, 2018: PLoS Pathogens
D Jian, W Wang, X Zhou, Z Jia, J Wang, M Yang, W Zhao, Z Jiang, X Hu, J Zhu
AIM: Endothelial recovery, or re-endothelialization, plays an important role in intimal hyperplasia and atherosclerosis after endothelial injury. Studying the mechanisms of re-endothelialization and strategies to promote efficient endothelial recovery are still needed. Interferon-induced protein 35 (IFI35) is an IFN-γ-induced protein that plays important roles in the antivirus-related immune-inflammatory response. In this study, we tested whether overexpression IFI35 affects the proliferation and migration of endothelial cells (ECs) and re-endothelialization...
January 19, 2018: Acta Physiologica
Tuba Sevimoglu, Beste Turanli, Ceyhun Bereketoglu, Kazim Yalcin Arga, Ayse Serap Karadag
Psoriasis is a complex autoimmune disease with multiple genes and proteins being involved in its pathogenesis. Despite the efforts performed to understand mechanisms of psoriasis pathogenesis and to identify diagnostic and prognostic targets, disease-specific and effective biomarkers were still not available. This study is compiled regarding clinical validation of computationally proposed biomarkers at gene and protein expression levels through qRT-PCR and ELISA techniques using skin biopsies and blood plasma...
March 20, 2018: Gene
Hawley C Pruitt, Brandon J Metge, Shannon E Weeks, Dongquan Chen, Shi Wei, Robert A Kesterson, Lalita A Shevde, Rajeev S Samant
The process of organ development requires a delicate balance between cellular plasticity and differentiation. This balance is disrupted in cancer initiation and progression. N-Myc and STAT interactor (NMI: human or Nmi: murine) has emerged as a relevant player in the etiology of breast cancer. However, a fundamental understanding of its relevance to normal mammary biology is lacking. To gain insight into its normal function in mammary gland, we generated a mammary-specific Nmi knockout mouse model. We observed that Nmi protein expression is induced in mammary epithelium at the onset of pregnancy, in luminal cells and persists throughout lactation...
March 2018: Oncogene
Laura Buttrum, Lindsey Ledbetter, Rama Cherla, Yan Zhang, William J Mitchell, Guoquan Zhang
To understand the role of class I major histocompatibility complex (MHC-I) and class II MHC (MHC-II) antigen presentation pathways in host defense against Coxiella burnetii infection, we examined whether MHC-I or MHC-II deficiency in mice would significantly influence their susceptibility to virulent C. burnetii Nine Mile phase I (NMI) infection. The results indicate that NMI infection induced more severe disease in both MHC-I-deficient and MHC-II-deficient mice than in wild-type (WT) mice, while only MHC-I-deficient mice developed a severe persistent infection and were unable to control bacterial replication...
April 2018: Infection and Immunity
Jake Jk Goh
BACKGROUND: Since 2016, the Naval Diving Unit (NDU) of the Republic of Singapore Navy (RSN) has instituted a smoking cessation trial program for their trainees, instituting a blanket ban on smoking during training hours in order to promote smoking cessation and create a smoke-free culture among its servicemen. For the rest of RSN personnel, they would attend a more costly, established Health Promotion Board (HPB) smoking cessation program, which employs social support strategies, while they undergo basic training in the Navy Military Experts Institute (NMI)...
November 2017: Undersea & Hyperbaric Medicine: Journal of the Undersea and Hyperbaric Medical Society, Inc
Sheffali Gulati, Harsh Patel, Biswaroop Chakrabarty, Rachana Dubey, N K Arora, R M Pandey, Vinod K Paul, Konanki Ramesh, Vyshakh Anand, Ankit Meena
Introduction: There is shortage of specialists for the diagnosis of children with neuromotor impairments (NMIs), especially in resource limited settings. Existing International Clinical Epidemiology Network (INCLEN) instrument for diagnosing NMI have been validated for children aged 2-9 years. The current study modified the same including wider symptomatology and age group (1 month to 18 years). Methods: The Modified INCLEN diagnostic tool (INDT) was developed by a team of experts by modifying the existing tool to widen the age range (1 month to 18 years) and include broader symptomatology (inclusion of milestones from the first 2 years of life and better elucidation of cerebellar and extrapyramidal features) in a tertiary care teaching hospital of North India between January and April 2015...
2017: Frontiers in Public Health
A J Fenwick, J L Wevrett, K M Ferreira, A M Denis-Bacelar, A P Robinson
In External Beam Radiotherapy, National Metrology Institutes (NMIs) play a critical role in the delivery of accurate absorbed doses to patients undergoing treatment. In contrast for nuclear medicine the role of the NMI is less clear and although significant work has been done in order to establish links for activity measurement, the calculation of administered absorbed doses is not traceable in the same manner as EBRT. Over recent decades the use of novel radiolabelled pharmaceuticals has increased dramatically...
November 11, 2017: Applied Radiation and Isotopes
Yu-Hsiang Fu, Chung-Yuan Huang, Chuen-Tsai Sun
The authors use four criteria to examine a novel community detection algorithm: (a) effectiveness in terms of producing high values of normalized mutual information (NMI) and modularity, using well-known social networks for testing; (b) examination, meaning the ability to examine mitigating resolution limit problems using NMI values and synthetic networks; (c) correctness, meaning the ability to identify useful community structure results in terms of NMI values and Lancichinetti-Fortunato-Radicchi (LFR) benchmark networks; and (d) scalability, or the ability to produce comparable modularity values with fast execution times when working with large-scale real-world networks...
2017: PloS One
Jingjing Hou, Shihao Jiang, Jiabao Zhao, Dong Zhu, Xinmeng Zhao, Jian-Chun Cai, Si Qing Zhang
NF-κB is a major regulator of gene transcription involved in immune, inflammation, apoptosis and stress responses. However, the regulation of NF-κB is not completely understood. Here, we report that the N-Myc and STATs Interactor (NMI), an IFN-inducible protein, is an important negative regulator of NF-κB activity. We found that NMI negatively regulates TNF-α-induced IL-6 and IL-1β production in HeLa cells. Overexpression of NMI inhibits NF-κB transcriptional activity, in contrast, depletion of NMI by shRNA increases NF-κB transcriptional activity...
November 6, 2017: Scientific Reports
Ashok Keerthi, Boya Radha, Daniele Rizzo, Hao Lu, Valentin Diez Cabanes, Ian Cheng-Yi Hou, David Beljonne, Jérôme Cornil, Cinzia Casiraghi, Martin Baumgarten, Klaus Müllen, Akimitsu Narita
Edge functionalization of bottom-up synthesized graphene nanoribbons (GNRs) with anthraquinone and naphthalene/perylene monoimide units has been achieved through a Suzuki coupling of polyphenylene precursors bearing bromo groups, prior to the intramolecular oxidative cyclo-dehydrogenation. High efficiency of the substitution has been validated by MALDI-TOF MS analysis of the functionalized precursors and FT-IR, Raman, and XPS analyses of the resulting GNRs. Moreover, AFM measurements demonstrated the modulation of the self-assembling behavior of the edge-functionalized GNRs, revealing that GNR-PMI formed an intriguing rectangular network...
November 22, 2017: Journal of the American Chemical Society
Esther Sok Hwee Cheow, Woo Chin Cheng, Terence Yap, Bamaprasad Dutta, Chuen Neng Lee, Dominique P V de Kleijn, Vitaly Sorokin, Siu Kwan Sze
The lack of precise biomarkers that identify patients at risk for myocardial injury and stable angina delays administration of optimal therapy. Hence, the search for noninvasive biomarkers that could accurately stratify patients with impending heart attack, from patients with stable coronary artery disease (CAD), is urgently needed in the clinic. Herein, we performed comparative quantitative proteomics on whole plasma sampled from patients with stable angina (NMI), acute myocardial infarction (MI), and healthy control subjects (Ctrl)...
January 5, 2018: Journal of Proteome Research
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