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Amélie Bonnet-Garnier, Kiên Kiêu, Tiphaine Aguirre-Lavin, Krisztina Tar, Pierre Flores, Zichuan Liu, Nathalie Peynot, Martine Chebrout, András Dinnyés, Véronique Duranthon, Nathalie Beaujean
Changes to the spatial organization of specific chromatin domains such as constitutive heterochromatin have been studied extensively in somatic cells. During early embryonic development, drastic epigenetic reprogramming of both the maternal and paternal genomes, followed by chromatin remodeling at the time of embryonic genome activation (EGA), have been observed in the mouse. Very few studies have been performed in other mammalian species (human, bovine, or rabbit) and the data are far from complete. During this work, we studied the three-dimensional organization of pericentromeric regions during the preimplantation period in the rabbit using specific techniques (3D-FISH) and tools (semi-automated image analysis)...
April 18, 2018: Chromosoma
Christelle Mbondji-Wonje, Ming Dong, Xue Wang, Jiangqin Zhao, Viswanath Ragupathy, Ana M Sanchez, Thomas N Denny, Indira Hewlett
Functional mapping of the 5'LTR has shown that the U3 and the R regions (U3R) contain a cluster of regulatory elements involved in the control of HIV-1 transcription and expression. As the HIV-1 genome is characterized by extensive variability, here we aimed to describe mutations in the U3R from various HIV-1 clades and CRFs in order to highlight strain specific differences that may impact the biological properties of diverse HIV-1 strains. To achieve our purpose, the U3R sequence of plasma derived virus belonging to different clades (A1, B, C, D, F2) and recombinants (CRF02_AG, CRF01_AE and CRF22_01A1) was obtained using Illumina technology...
2018: PloS One
Yoshitaka Tamaki, Akemi Shodai, Toshifumi Morimura, Ryota Hikiami, Sumio Minamiyama, Takashi Ayaki, Ikuo Tooyama, Yoshiaki Furukawa, Ryosuke Takahashi, Makoto Urushitani
Aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is implicated in the pathogenesis of sporadic and certain familial forms of amyotrophic lateral sclerosis (ALS), suggesting elimination of TDP-43 aggregates as a possible therapeutic strategy. Here we generated and investigated a single-chain variable fragment (scFv) derived from the 3B12A monoclonal antibody (MAb) that recognises D247 of the TDP-43 nuclear export signal, an epitope masked in the physiological state. In transfected HEK293A cells, 3B12A scFv recapitulated the affinity of the full-length MAb to mislocalised TDP-43 with a defective nuclear localising signal and to a TDP-43 inclusion mimic with cysteine-to-serine substitution at RRM1...
April 16, 2018: Scientific Reports
Junice Yi Siu Ng, Roy Kum Wah Chan, Martin Tze-Wei Chio, Raymond Boon Tar Lim, David Koh, Mee Lian Wong
PURPOSE: The objective of this study was to evaluate the efficacy of a behavioral intervention in increasing secondary abstinence and safer sex among heterosexually active adolescents aged 16-19 years. METHODS: This was a randomized controlled trial conducted at the only national sexually transmitted infection clinic in Singapore. The intervention focused on information giving, motivation, and skills building to abstain or practice safer sex. The outcome measures were self-reported secondary abstinence, consistent condom use, and keeping to one partner in the past 6 months over a 12-month period...
April 13, 2018: Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine
Raymond Boon Tar Lim, Olive N Y Cheung, Dede Kam Tyng Tham, Hanh Hao La, Thein Than Win, Roy Chan, Mee Lian Wong
BACKGROUND: There is an increasing global movement of foreign female entertainment workers (FEWs), a hard-to-reach population vulnerable to HIV/STIs. This paper described the needs assessment phase before intervention implementation where the socio-organisation, sexual risk behaviours and access to health services of foreign FEWs in Singapore were explored. We also highlighted how qualitative inquiry, census enumeration technique and community-based engagement approaches were used to gain access and to develop a culturally appropriate STI prevention intervention...
April 16, 2018: Globalization and Health
Clément Boidin, Sophie Jenck, Laurent Bourguignon, Sejad Torkmani, Aurore Roussey-Jean, Stanislas Ledochowski, Lucie Marry, Nacim Ammenouche, Hervé Dupont, Frédéric Marçon, Bernard Allaouchiche, Julien Bohé, Alain Lepape, Sylvain Goutelle, Arnaud Friggeri
Amikacin antimicrobial effect has been correlated with the ratio of the peak concentration (Cmax) to the minimum inhibitory concentration. A target Cmax ≥ 60-80 mg/L has been suggested. It has been shown that such target is not achieved in a large proportion of critically ill patients in intensive care units. A retrospective analysis was performed to examine the determinants of Cmax ≥ 80 mg/L on the first peak in 339 critically ill patients treated by amikacin. The influence of available variables on Cmax target attainment was analyzed using a classification and regression tree (CART) and logistic regression...
April 16, 2018: Fundamental & Clinical Pharmacology
Masaki Takemura, Takeshi Nakahara, Akiko Hashimoto-Hachiya, Masutaka Furue, Gaku Tsuji
Atopic dermatitis (AD) is a common inflammatory skin disease. Recent studies have revealed the involvement of T helper (Th)2 cytokines including Interleukin 4 (IL-4) in the pathogenesis of AD. Since epidermal Langerhans cells (LCs) and dermal myeloid dendritic cells (DCs) produce CCL17 and CCL22 that chemoattract Th2 cells, interfering with CCL17 and CCL22 production from LCs and dermal myeloid DCs may be beneficial in the treatment of AD. To investigate this, we stimulated murine bone marrow-derived DCs (BMDCs) with IL-4...
April 12, 2018: International Journal of Molecular Sciences
Martin F Bachmann, Andris Zeltins, Gints Kalnins, Ina Balke, Nina Fischer, Ana Rostaher, Kaspars Tars, Claude Favrot
No abstract text is available yet for this article.
March 28, 2018: Journal of Allergy and Clinical Immunology
Liang Sun, Kai Zhang, Weiwei Zhai, Haiying Li, Haitao Shen, Zhengquan Yu, Gang Chen
This study aimed to determine the role of TAR DNA binding protein-43 (TDP-43) in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) and its underlying mechanisms. After ICH, expression of TDP-43 in the nucleus was significantly decreased, and its expression in the cytoplasm increased both in vivo and in vitro , which indicates that TDP-43 translocates from the nucleus to the cytoplasm during SBI after ICH. In addition, mutations at S409/410 of TDP-43 could inhibit its phosphorylation, attenuate nuclear loss, and abolish the increase in neuronal apoptosis in the subcortex...
2018: Frontiers in Cellular Neuroscience
Giuseppe Militello, Mohammed Rabiul Hosen, Yuliya Ponomareva, Pascal Gellert, Tyler Weirick, David John, Sajedah Mahmoud Hindi, Kamel Mamchaoui, Vincent Mouly, Claudia Döring, Lidan Zhang, Miki Nakamura, Ashok Kumar, So-Ichiro Fukada, Stefanie Dimmeler, Shizuka Uchida
Myogenesis is a complex process required for skeletal muscle formation during embryonic development and for regeneration and growth of myofibers in adults. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) play key roles in regulating cell fate decision and function in various tissues. However, the role of lncRNAs in the regulation of myogenesis remains poorly understood. In this study, we identified a novel muscle-enriched lncRNA called "Myolinc (AK142388)", which we functionally characterized in the C2C12 myoblast cell line...
April 3, 2018: Journal of Molecular Cell Biology
Luca Lo Piccolo, Rosa Bonaccorso, Andrea Attardi, Lorenzo Li Greci, Giulia Romano, Martina Sollazzo, Giorgio Giurato, Antonia Maria Rita Ingrassia, Fabian Feiguin, Davide F V Corona, Maria Cristina Onorati
Over the past decade, evidence has identified a link between protein aggregation, RNA biology, and a subset of degenerative diseases. An important feature of these disorders is the cytoplasmic or nuclear aggregation of RNA-binding proteins (RBPs). Redistribution of RBPs, such as the human TAR DNA-binding 43 protein (TDP-43) from the nucleus to cytoplasmic inclusions is a pathological feature of several diseases. Indeed, sporadic and familial forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration share as hallmarks ubiquitin-positive inclusions...
April 4, 2018: International Journal of Molecular Sciences
Bert M Verheijen, Kiyomitsu Oyanagi, Fred W van Leeuwen
Guam parkinsonism-dementia complex (G-PDC) is an enigmatic neurodegenerative disease that is endemic to the Pacific island of Guam. G-PDC patients are clinically characterized by progressive cognitive impairment and parkinsonism. Neuropathologically, G-PDC is characterized by abundant neurofibrillary tangles, which are composed of hyperphosphorylated tau, marked deposition of 43-kDa TAR DNA-binding protein, and neuronal loss. Although both genetic and environmental factors have been implicated, the etiology and pathogenesis of G-PDC remain unknown...
2018: Frontiers in Neurology
Chia-You Lai, Yu-Ju Liu, Hsing-Lin Lai, Hui-Mei Chen, Hung-Chi Kuo, Yu-Ping Liao, Yijuang Chern
The A2A adenosine receptor (A2A R) and D2 dopamine receptor (D2 R) are two G-protein-coupled receptors that can form dimers and negatively regulate their partners. TAR DNA-binding protein (TDP-43) is a nuclear protein that has been implicated in amyotrophic lateral sclerosis (ALS). Mislocalization of TDP-43 from the nucleus to the cytoplasm is an early step of TDP-43 proteinopathy. Our previous studies indicated that A2A R is a potential drug target for ALS because treatment with an A2A R agonist (JMF1907; a T1-11 analog) prevents reactive oxygen species (ROS)-induced TDP-43 mislocalization in a motor neuron cell line (NSC34) and delays motor impairment in a TDP-43 transgenic ALS mouse model...
2018: Frontiers in Neuroscience
Christine Leibiger, Jana Deisel, Andreas Aufschnaiter, Stefanie Ambros, Maria Tereshchenko, Bert M Verheijen, Sabrina Büttner, Ralf J Braun
The accumulation of protein aggregates in neurons is a typical pathological hallmark of the motor neuron disease amyotrophic lateral sclerosis (ALS) and of frontotemporal dementia (FTD). In many cases, these aggregates are composed of the 43 kDa TAR DNA-binding protein (TDP 43). Using a yeast model for TDP 43 proteinopathies, we observed that the vacuole (the yeast equivalent of lysosomes) markedly contributed to the degradation of TDP 43. This clearance occurred via TDP 43-containing vesicles fusing with the vacuole through the concerted action of the endosomal-vacuolar (or endolysosomal) pathway and autophagy...
March 21, 2018: Microbial Cell
Yosuke Inoue, Hitoshi Matsuda, Atsushi Omura, Yoshimasa Seike, Kyokun Uehara, Hiroaki Sasaki, Junjiro Kobayashi
OBJECTIVES: Aggressive total arch replacement (TAR) to obtain thrombosis of the distal false lumen (FL) in patients with Stanford Type A acute aortic dissection, particularly with a patent FL at the descending aorta, is discussed. The aim of this study was to examine the efficacy of our strategy. METHODS: In the last 20 years, we retrospectively reviewed the records of 518 patients with Type A acute aortic dissection who underwent an emergent surgery. Among them, 290 patients with a preoperative patent FL at the descending aorta were enrolled in this study...
March 28, 2018: European Journal of Cardio-thoracic Surgery
Reena Rai, Manjunath M Shenoy, Vishalakshi Viswanath, Nilendu Sarma, Imran Majid, Sunil Dogra
Venous leg ulcers are the most common form of non-healing leg ulcers. They are subjected to treatments such as topical medications, dressings, and compression therapies. This can lead to exposure to a number of allergens with subsequent sensitisation and contact dermatitis of the regional skin. This may contribute to the poor ulcer healing. To detect the various contact sensitisers in patients with venous leg ulcers through patch testing, patients from 6 centres across India with venous leg ulcers of longer than 6 weeks duration were enrolled for the study...
March 30, 2018: International Wound Journal
Brandon M Stewart, Michael E Miller, David M Kempisty, John Stubbs, Willie F Harper
The presence of tartrazine (TAR) in the water cycle poses serious threats to human health. This study investigated the used of light emitting diodes (LEDs) in the advanced oxidation of TAR under different pH and duty cycle (DC) conditions. The first order reaction rate constant for TAR oxidation was positively correlated with DC, negatively correlated with pH, and typically greatest at pH 6. Chemical byproduct analysis indicated that OH addition, H abstraction, and electron transfer without molecule transfer were among the relevant reaction mechanisms for TAR degradation...
March 2018: Water Science and Technology: a Journal of the International Association on Water Pollution Research
Mee Lian Wong, Alvin Kuo Jing Teo, Bee Choo Tai, Alwyn Mao Tong Ng, Raymond Boon Tar Lim, Dede Kam Tyng Tham, Nashwinder Kaur, Rayner Kay Jin Tan, Sarath Kros, Savun Touch, Maryan Chhit, Ian Lubek
BACKGROUND: Following Cambodia's implementation of the 100% condom use program with enforcement of condom use and STI treatment services for sex workers in 2001, sexually transmitted infection and HIV declined markedly. In 2008, Cambodia implemented a law to ban brothel-based sex work. We reported trends in unprotected vaginal intercourse with sex workers among heterosexual men buying sex before (2003-2008) and after (2009-2012) the brothel ban in Cambodia. We also determined the association of brothel ban with these men's reports of unprotected intercourse with sex workers...
March 27, 2018: BMC Public Health
Tamar Gefen, Saman S Ahmadian, Qinwen Mao, Garam Kim, Mustafa Seckin, Borna Bonakdarpour, Eliana Marisa Ramos, Giovanni Coppola, Rosa Rademakers, Emily Rogalski, Alfred Rademaker, Sandra Weintraub, M-Marsel Mesulam, Changiz Geula, Eileen H Bigio
This study investigated the presence of combined pathologies in a large cohort of autopsies that show a primary pathologic diagnosis of phosphorylated 43-kDa TAR DNA-binding protein (FTLD-TDP), the majority of which portrayed clinical phenotypes consistent with primary progressive aphasia or behavioral variant frontotemporal dementia (bvFTD). Thirty-eight cases with FTLD-TDP (30 type-A and 8 type-C) were identified to determine characteristic differences between cases with and without combined pathologies. Findings indicated that combined pathologies co-occur with FTLD-TDP type-A at a high frequency (50%)-greater than when compared to FTLD-TDP type-C cases (12...
March 23, 2018: Journal of Neuropathology and Experimental Neurology
Hao Ke, Limin Zhao, Honglei Zhang, Xu Feng, Haibo Xu, Junjun Hao, Shaowei Wang, Qin Yang, Li Zou, Xiaosan Su, Liqiong Wang, Chunlian Wu, Yang Wang, Jianyun Nie, Baowei Jiao
Aberrant alternative splicing has been highlighted as a potential hallmark of cancer. Here, we identify TDP43 (TAR DNA-binding protein 43) as an important splicing regulator responsible for the unique splicing profile in triple-negative breast cancer (TNBC). Clinical data demonstrate that TDP43 is highly expressed in TNBC with poor prognosis. Knockdown of TDP43 inhibits tumor progression, including proliferation and metastasis, and overexpression of TDP43 promotes proliferation and malignancy of mammary epithelial cells...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
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