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Sanjay Tewari, George Renney, John Brewin, Kate Gardner, Fenella Kirkham, Baba Inusa, James E Barrett, Stephan Menzel, Swee Lay Thein, Malcolm Ward, David C Rees
Silent cerebral infarction is the commonest neurological abnormality in children with sickle cell anemia, affecting 30-40% 14 year olds. There are no known biomarkers to identify children with silent cerebral infarcts and the pathological basis is also unknown. We used an unbiased proteomic discovery approach to identify plasma proteins differing in concentration between children with and without silent cerebral infarcts. Clinical parameters and plasma samples were analysed from 51 children (mean age 11.8 years, range 6-18) with sickle cell anemia (HbSS)...
March 15, 2018: Haematologica
Chia-Sheng Pai, Pranao K Sharma, Hsien-Ting Huang, Srivaishnavi Loganathan, Heng Lin, Yu-Luan Hsu, Sarayut Phasuk, Ingrid Y Liu
The genetic and molecular basis underlying fear memory formation is a key theme in anxiety disorder research. Because activating transcription factor 3 ( ATF3 ) is induced under stress conditions and is highly expressed in the hippocampus, we hypothesize that ATF3 plays a role in fear memory formation. We used fear conditioning and various other paradigms to test Atf3 knockout mice and study the role of ATF3 in processing fear memory. The results demonstrated that the lack of ATF3 specifically enhanced the expression of fear memory, which was indicated by a higher incidence of the freeze response after fear conditioning, whereas the occurrence of spatial memory including Morris Water Maze and radial arm maze remained unchanged...
2018: Frontiers in Molecular Neuroscience
Eisuke Miyauchi, Takuya Furuta, Sumio Ohtsuki, Masanori Tachikawa, Yasuo Uchida, Hemragul Sabit, Wataru Obuchi, Tomoko Baba, Michitoshi Watanabe, Tetsuya Terasaki, Mitsutoshi Nakada
Molecular biomarkers in blood are needed to aid the early diagnosis and clinical assessment of glioblastoma (GBM). Here, in order to identify biomarker candidates in plasma of GBM patients, we performed quantitative comparisons of the plasma proteomes of GBM patients (n = 14) and healthy controls (n = 15) using SWATH mass spectrometry analysis. The results were validated by means of quantitative targeted absolute proteomics analysis. As a result, we identified eight biomarker candidates for GBM (leucine-rich alpha-2-glycoprotein (LRG1), complement component C9 (C9), C-reactive protein (CRP), alpha-1-antichymotrypsin (SERPINA3), apolipoprotein B-100 (APOB), gelsolin (GSN), Ig alpha-1 chain C region (IGHA1), and apolipoprotein A-IV (APOA4))...
2018: PloS One
Ye Li, Lei Chen, Jun Zhou, Xiurong Su, Taiwu Li
The gelsolin family proteins are best known for involvement in cytoskeletal rearrangement by controlling actin organization during a variety of cellular processes. Previously, a 1962 bp cDNA encoding a 41.7 kDa protein with three gelsolin-like domains (G domains) from Dendrorhynchus zhejiangensis was identified and named as DzGSN. In this study, the sequence and function of a novel member of the gelsolin family proteins from D. zhejiangensis have been analyzed. Sequence alignment indicates that DzGSN is highly homologous to human gelsolin (35% identity) and human CapG (36% identity)...
March 2, 2018: Protein Journal
Xiaobai Liu, Jian Zheng, Yixue Xue, Chengbin Qu, Jiajia Chen, Zhenhua Wang, Zhen Li, Lei Zhang, Yunhui Liu
Long non-coding RNA (lncRNA) dysregulation is involved in tumorigenesis and regulation of diverse cellular processes in gliomas. lncRNA SNHG12 is upregulated and promotes cell growth in human osteosarcoma cells. TAR-DNA binding protein 43 (TDP43) functions as an oncogene in various tumors by modulating RNA expression. Downregulation of TDP43 or SNHG12 significantly inhibited malignant biological behaviors of glioma cells. miR-195, downregulated in glioma tissues and cells, significantly impaired the malignant progression of glioma cells...
March 2, 2018: Molecular Therapy. Nucleic Acids
Nikolett Kis-Bicskei, Bálint Bécsi, Ferenc Erdődi, Robert C Robinson, Beáta Bugyi, Tamás Huber, Miklós Nyitrai, Gábor Csaba Talián
The actin cytoskeleton fulfills numerous key cellular functions, which are tightly regulated in activity, localization, and temporal patterning by actin binding proteins. Tropomyosins and gelsolin are two such filament-regulating proteins. Here, we investigate how the effects of tropomyosins are coupled to the binding and activity of gelsolin. We show that the three investigated tropomyosin isoforms (Tpm1.1, Tpm1.12, and Tpm3.1) bind to gelsolin with micromolar or submicromolar affinities. Tropomyosin binding enhances the activity of gelsolin in actin polymerization and depolymerization assays...
February 27, 2018: Biophysical Journal
Juhura G Almazi, Peter Pockney, Craig Gedye, Nathan D Smith, Hubert Hondermarck, Nicole M Verrills, Matthew D Dun
BACKGROUND: Optimized blood collection tubes (BCT) have been developed to expand the utility of plasma cell free DNA (cfDNA) and are in clinical use. The appropriateness of plasma collected and stored in these tubes for proteomic analysis is unknown. METHODS: Paired blood samples were collected in BCT and traditional K3EDTA (EDTA) tubes from healthy controls, and from colorectal cancer patients (CRC) before and after surgery, and stored for between 45 minutes and 48 hours at room temperature...
February 24, 2018: Proteomics. Clinical Applications
Isabel Benavente-Fernandez, Juan J Ramos-Rodriguez, Carmen Infante-Garcia, Gema Jimenez-Gomez, Alfonso Lechuga-Sancho, Simon Lubian-Lopez, Monica Garcia-Alloza
Hypoxic-ischemic encephalopathy (HIE) is a severe neonatal complication responsible for ∼23% of all neonatal deaths. Also, 30-70% of these patients will suffer lifetime disabilities, including learning impairment, epilepsy or cerebral palsy. However, biomarkers for HIE screening, or monitoring disease progression are limited. Herein, we sought to evaluate the clinical usefulness of plasma-type gelsolin (pGSN) and amyloid-beta (Aβ) 40 and 42 as prognostic biomarkers for HIE. pGSN has been previously suggested as a feasible marker in other brain injuries and amyloid-beta 40 and 42 are classically assessed in neurodegenerative diseases...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Saimir Hoxha, Ecem Kaya-Sezginer, Filiz Bakar-Ates, Oğuz Köktürk, Ufuk Toygar-Memikoğlu
BACKGROUND: The purpose of this study was to investigate the effect of semi-rapid maxillary expansion (SRME) orthodontic treatment on biomarkers and respiratory parameters in children with obstructive sleep apnea syndrome (OSAS) and maxillary transverse deficiency. METHODS: Thirty children with OSAS were included in this study. Fifteen children were enrolled as control, and 15 children were subjected to SRME orthodontic treatment method for 5 months. Beside respiratory parameters, pharyngeal area, dental arch, and postero-anterior widths and the levels of OSAS biomarkers in serum and urine were measured...
February 17, 2018: Sleep & Breathing, Schlaf & Atmung
Heather L Miears, David R Gruber, Nicholas M Horvath, John M Antos, Jeff Young, Johann P Sigurjonsson, Maya L Klem, Erin A Rosenkranz, Mark Okon, Christopher James McKnight, Liliya Vugmeyster, Serge L Smirnov
Plants utilize multiple isoforms of villin, an F-actin regulating protein with an N-terminal gelsolin-like core and a distinct C-terminal headpiece domain. Unlike their vertebrate homologs, plant villins have a much longer linker polypeptide connecting the core and headpiece. Moreover, the linker-headpiece connection region in plant villins lack sequence homology to the vertebrate villin sequences. It is unknown to what extent the plant villin headpiece structure and function resemble those of the well-studied vertebrate counterparts...
February 14, 2018: Biochemistry
Shan-Shan Shi, Xiao-Jie Yue, Dong-Yan Zhao, Jia-Jie Fan, Jian-Guo Xu, Xi-Wang Liu, Bao-Li Cheng, Xiang-Ming Fang, Jie Fan, Qiang Shu
BACKGROUND: Acute kidney injury (AKI) after cardiopulmonary bypass (CPB) is a common complication especially in pediatric population. Plasma gelsolin (pGSN) is an anti-inflammatory factor through binding with actin and pro-inflammatory cytokines in circulation. Decrease in pGSN has been reported in some pathologic conditions. The purpose of the study was to determine the alterations of pGSN level in infants and young children after CPB and the role of pGSN as a predictor for the morbidity and severity of post-CPB AKI...
February 9, 2018: World Journal of Pediatrics: WJP
Sedat Per, Mehmet Kose, Ahmet Ozdemir, Dilek Pandir
Tissues and organs get exposed to high oxygen (O2) supply in hyperoxia conditions. The goal of this research was to investigate the protective effect of actin binding protein gelsolin on hyperoxia-induced hepatotoxicity through histopathology and measurement of oxidative stress parameters and DNA damage in a neonatal Wistar albino rats. The pups were randomly separated to four equal groups such as: normoxia control group (NC), normoxia plus gelsolin group (NG, 10 ng/kg bw/day gelsolin), hyperoxia (≥85% O2) group (HC), hyperoxia plus gelsolin group (HG, ≥85% O2; 10 ng/kg bw/day gelsolin)...
January 26, 2018: Environmental Toxicology and Pharmacology
Da-Peng Yun, Yu-Qi Wang, De-Long Meng, Yuan-Yuan Ji, Ju-Xiang Chen, Hong-Yan Chen, Da-Ru Lu
Glioma is the most aggressive and malignant primary brain tumor in adults. In the present study, we identified a vital oncoprotein, capping actin protein, gelsolin-like (CapG), and investigated its roles in the prognosis, proliferation and metastasis in glioma. The mRNA and protein levels of CapG were significantly increased in human glioma, and higher CapG expression was an independent prognostic factor for predicting unfavorable prognosis. The expression level of CapG was found to be associated with several common molecular features of glioblastoma (GBM; WHO grade IV glioma) in The Cancer Genome Atlas (TCGA) cohort...
January 22, 2018: Oncology Reports
Robert Bucki, Bonita Durnaś, Marzena Wątek, Ewelina Piktel, Katrina Cruz, Przemysław Wolak, Paul B Savage, Paul A Janmey
The response of the human immune system to most bacterial infections results in accumulation of neutrophils at infection sites that release a significant quantity of DNA and F-actin. Both are negatively charged polyelectrolytes that can interact with positively charged host defense molecules such as cathelicidin-delivered LL-37 peptide or other cationic antibiotic agents. Evaluation of the ability of bacterial outgrowth (using luminescence measurements or counting colony-forming units) to form a biofilm (quantified by crystal violet staining) and analysis of the structure of DNA/F-actin network by optical microscopy in human pus samples treated with different antibiotics in combination with plasma gelsolin, DNAse 1, and/or poly-aspartic acid revealed that bactericidal activity of most tested antibacterial agents increases in the presence of DNA/F-actin depolymerizing factors...
2018: Infection and Drug Resistance
Zhouwei Xu, Aven Lee, Amanda Nouwens, Robert David Henderson, Pamela Ann Mccombe
Mass spectrometry was used to study blood samples from patients with amyotrophic lateral sclerosis (ALS) and healthy controls. Addenbrooke's cognitive examination-III (ACE-III) was used to test for cognitive impairment (CI). Nano liquid chromatography and time of flight mass spectrometry (MS) were performed on samples from 42 ALS patients and 18 healthy controls. SWATH™ proteomic analysis was utilized to look for differences between groups. Western blot analysis was used to study levels of 4 proteins, selected as being of possible interest in ALS, in the MS discovery cohort and a second validation group of 10 ALS patients and 10 healthy controls...
January 31, 2018: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Samsuzzoha Mondal, Amitava Chandra, Ravindra Venkatramani, Ankona Datta
We present a systematic experimental and computational study of phospholipid induced peptide coil-helix transitions which are relevant in the context of proteins mediating cytoskeletal rearrangement via membrane binding. We developed a sensitive Förster resonance energy transfer (FRET) based assay to address whether coil-helix transitions in phospholipid binding motifs of actin-binding proteins can be induced by physiologically-relevant concentrations (1-20 μM) of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) phospholipids...
January 24, 2018: Faraday Discussions
Jaime Jacqueline Jayapalan, Cheng-Siang Lee, Ching Chin Lee, Khoon Leong Ng, Sarni Mat Junit, Onn Haji Hashim
No abstract text is available yet for this article.
January 17, 2018: Clinical Biochemistry
Renu Garg, Nagesh Peddada, Kunzes Dolma, Neeraj Khatri, Ashish Ashish
Plasma gelsolin (pGSN), a protein primarily involved in clearance of circulating actin filaments, is an upcoming novel biomarker. Its level changes in multiple disease and injury conditions, attributable mainly to its consumption during actin clearance, the endogenous regulation of its expression, however, remains elusive as well as unexplored. Here, we are reporting first isolation of the promoter region of pGSN gene and investigation of its transcriptional regulation during pregnancy (a natural process associated with a well programmed injury course of parturition)...
January 17, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
J E Araújo, H López-Fernández, M S Diniz, Pedro M Baltazar, Luís Campos Pinheiro, Fernando Calais da Silva, Mylène Carrascal, Paula Videira, H M Santos, J L Capelo
This study aimed to assess the benefits of dithiothreitol (DTT)-based sample treatment for protein equalization to assess potential biomarkers for bladder cancer. The proteome of plasma samples of patients with bladder carcinoma, patients with lower urinary tract symptoms (LUTS) and healthy volunteers, was equalized with dithiothreitol (DTT) and compared. The equalized proteomes were interrogated using two-dimensional gel electrophoresis and matrix assisted laser desorption ionization time of flight mass spectrometry...
April 1, 2018: Talanta
Zoltán Horváth-Szalai, Péter Kustán, Balázs Szirmay, Ágnes Lakatos, Per Hjort Christensen, Tamás Huber, Beáta Bugyi, Diána Mühl, Andrea Ludány, Attila Miseta, Gábor L Kovács, Tamás Kőszegi
BACKGROUND: Simultaneous determination of the two main actin scavenger proteins in sepsis has not been investigated until now. In our pilot study, we elucidated the predictive values of Gc globulin and gelsolin (GSN) in sepsis by comparing them to classic laboratory and clinical parameters. METHODS: A 5-day follow-up was performed, including 46 septic patients, 28 non-septic patients and 35 outpatients as controls. Serum Gc globulin and GSN levels were determined by automated immune turbidimetric assay on a Cobas 8000/c502 analyzer...
January 10, 2018: Clinical Chemistry and Laboratory Medicine: CCLM
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