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Michael P Whyte, Emilina Lim, William H McAlister, Gary S Gottesman, Lien Trinh, Deborah J Veis, Vinieth N Bijanki, Matthew G Boden, Angela Nenninger, Steven Mumm, David Buchbinder
Pediatric granulomatous arthritis (PGA) refers to two formerly separate entities; autosomal dominant Blau syndrome (BS) and its sporadic phenocopy early-onset sarcoidosis (EOS). In 2001 BS and in 2005 EOS became explained by heterozygous mutations within the gene that encodes nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also called caspase recruitment domain-containing protein 15 (CARD15). NOD2 is a microbe sensor in leukocyte cytosol that activates and regulates inflammation. PGA is characterized by a triad of auto-inflammatory problems (dermatitis, uveitis, and arthritis) in early childhood, which suggests the causal NOD2/CARD15 mutations are activating defects...
June 22, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Haiguo Zhang, Guanli Song, Guanbo Song, Ruolei Li, Min Gao, Ling Ye, Chengfang Zhang
BACKGROUND: The aim of this study is to find the potential survival related DNA methylation signature capable of predicting survival time for acute myelocytic leukemia (AML) patients. METHODS: DNA methylation data were downloaded. DNA methylation signature was identified in the training group, and subsequently validated in an independent validation group. The overall survival of DNA methylation signature was performed. Functional analysis was used to explore the function of corresponding genes of DNA methylation signature...
2018: PloS One
Christina Yacoob, Miles Darnell Lange, Kristen Cohen, Kanan Lathia, Junli Feng, Jolene Glenn, Sara Carbonetti, Brian Oliver, Vladimir Vigdorovich, David Noah Sather, Leonidas Stamatatos
Broadly neutralizing HIV-1 antibodies (bNAbs) isolated from infected subjects display protective potential in animal models. Their elicitation by immunization is thus highly desirable. The HIV-1 envelope glycoprotein (Env) is the sole viral target of bnAbs, but is also targeted by binding, non-neutralizing antibodies. Env-based immunogens tested so far in various animal species and humans have elicited binding and autologous neutralizing antibodies but not bNAbs (with a few notable exceptions). The underlying reasons for this are not well understood despite intensive efforts to characterize the binding specificities of the elicited antibodies; mostly by employing serologic methodologies and monoclonal antibody isolation and characterization...
June 22, 2018: PLoS Pathogens
Sophie Crux, Jochen Herms, Mario M Dorostkar
Tcf4 is a transcription factor which regulates neurogenesis and neuronal migration in the brain. In humans, loss of function of Tcf4 leads to the rare neurodevelopmental disorder Pitt-Hopkins syndrome, which is characterized by intellectual disability, developmental delay and autistic behavior. We analyzed the consequences of functional loss of Tcf4 on dendritic spines in mature principal neurons. To this end, we crossed mice in which the DNA-binding domain of the Tcf4 gene is flanked by LoxP sites to mice expressing tamoxifen-inducible cre recombinase in a sparse subset of fluorescently labelled neurons (SlickV line)...
2018: PloS One
Nicolas Henry, Eva-Maria Krammer, Florian Stengel, Quentin Adams, François Van Liefferinge, Ellen Hubin, Rui Chaves, Rouslan Efremov, Ruedi Aebersold, Guy Vandenbussche, Martine Prévost, Vincent Raussens, Stéphanie Deroo
Apolipoprotein E (apoE) is a forefront actor in the transport of lipids and the maintenance of cholesterol homeostasis, and is also strongly implicated in Alzheimer's disease. Upon lipid-binding apoE adopts a conformational state that mediates the receptor-induced internalization of lipoproteins. Due to its inherent structural dynamics and the presence of lipids, the structure of the biologically active apoE remains so far poorly described. To address this issue, we developed an innovative hybrid method combining experimental data with molecular modeling and dynamics to generate comprehensive models of the lipidated apoE4 isoform...
June 22, 2018: PLoS Computational Biology
Arash Mirzahosseini, Tamás Pálla, Gábor Orgován, Gergő Tóth, Béla Noszál
Dopamine and 4 related compounds were studied by 1 H NMR-pH titrations and a case-tailored evaluation method. The resulting acid-base properties of dopamine are quantified in terms of 3 macroscopic and 12 microscopic protonation constants and the concomitant 3 interactivity parameters. The species- and site-specific basicities are interpreted by means of inductive and shielding effects through various intra- and intermolecular comparisons. The site-specific basicities determined this way are key parameters for the prediction of pharmacokinetic behavior and receptor-binding at the molecular level...
June 19, 2018: Journal of Pharmaceutical and Biomedical Analysis
Behrouz Golichenari, Rahim Nosrati, Aref Farokhi-Fard, Khalil Abnous, Farzam Vaziri, Javad Behravan
Tuberculosis is a major global health problem caused by the bacterium Mycobacterium tuberculosis (Mtb) complex. According to WHO reports, 53 million TB patients died from 2000 to 2016. Therefore, early diagnosis of the disease is of great importance for global health care programs. The restrictions of traditional methods have encouraged the development of innovative methods for rapid, reliable, and cost-effective diagnosis of tuberculosis. In recent years, aptamer-based biosensors or aptasensors have drawn great attention to sensitive and accessible detection of tuberculosis...
June 11, 2018: Biosensors & Bioelectronics
Mohammad M Hassan, Christopher M Carr
The effluent discharged by the textile dyehouses has a seriously detrimental effect on the aquatic environment. Some dyestuffs produce toxic decomposition products and the metal complex dyes release toxic heavy metals to watercourses. Of the dyes used in the textile industry, effluents containing reactive dyes are the most difficult to treat because of their high water-solubility and poor absorption into the fibers. A range of treatments has been investigated for the decolorization of textile effluent and the adsorption seems to be one of the cheapest, effective and convenient treatments...
June 14, 2018: Chemosphere
Sheng Cheng, Bin Zheng, Dongbao Yao, Shenglong Kuai, Jingjing Tian, Haojun Liang, Yunsheng Ding
Aptamers could be used to construct simple and effective biosensor because the conformational switch of aptamer upon target binding is easy to be transferred to optical or electrochemical signals. Nevertheless, we found that the binding between saxitoxin (STX) and aptamer (M-30f) is not accompanied with conformational switch. Here, the circular dichroism spectra, fluorophore and quencher labeled aptamer, and crystal violet-based assays were used to identify the binding way between STX and aptamer. The results show that the conformation of aptamer is stabilized in PBS buffer (10 mM phosphate buffer, 2...
June 11, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Douglas S Franciscato, Tiago A Matias, Jorge Shinohara, Josué M Gonçalves, Narcimário P Coelho, Cleverton S Fernandes, Ernani A Basso, Helena S Nakatani, Koiti Araki, Henrique E Toma, Vagner R de Souza
The Raman spectral profile of p-methylcarbohydrazonethioamide (MCHT) is completely changed due to strong SERS effects upon bonding onto gold nanoparticles surface, but some vibrational modes are further enhanced in the presence of Hg(II) ions. The lack of SERS response for most common metal ions indicates that the coordinating groups are interacting with the gold nanoparticles surface and not available for binding metal ions in solution, except for mercury ions. The selective enhancement of some vibrational modes is consistent with significant conformational changes upon binding of Hg(II) ion onto the AuNP@MCHT hybrid, as confirmed by TEM/EDS measurements, demonstrating its potentiality as a highly selective and sensitive SERS substrate...
June 14, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Shuyan Wu, Pak-Lam Yu, Dave Wheeler, Steve Flint
OBJECTIVES: The aim of this study was to determine the gene expression associated with the persistence of a Listeria monocytogenes stationary phase population when facing lethal nisin treatment METHODS: RNA Seq analysis was used for gene expression profiling of the persister cells in rich medium (persister TN) compared with untreated cells (non-persister).The results were confirmed using RT PCR. RESULTS: Functional genes associated with the persister populations were identified in multiple systems, such as heat shock related stress response, cell wall synthesis, ATP-binding cassette (ABC) transport system, phosphotransferase system (PTS system), and SOS/DNA repair...
June 19, 2018: Journal of Global Antimicrobial Resistance
Zhong-Min Dai, Yanan Xiong, Weiran He, Yukun Fang, Ye-Qing Qian, Xiao-Jing Zhu
Wnt signaling play important roles in a variety of developmental and pathological processes. Here we show that Wntless, the main regulator for Wnt secretion, is involved in the innate immune response of the giant freshwater prawn, Macrobrachium rosenbergii. The full-length cDNA of the prawn Wntless (named MrWntless) is 2173 bp in length and contains a 1602-bp open reading frame (ORF), which is conceptually translated into a 533-amino acids sequence. MrWntless protein contains a highly conserved Wnt-binding domain which is required for secretion of Wnt ligands, and exhibits 57-67% identity with known Wntless proteins of other animals...
June 19, 2018: Fish & Shellfish Immunology
Yuan Ma, Yuejie Zhu, Chao Wang, Delin Pan, Shuang Liu, Mengyi Yang, Zhangping Xiao, Xiantao Yang, Wenting Zhao, Xinyang Zhou, Yiding Li, Yufei Pan, Jing Sun, Shuhe Wang, Zhu Guan, Lihe Zhang, Zhenjun Yang
Lipid derivatives of nucleoside analogs have been highlighted for their potential for effective gene delivery. A novel class of nucleobase-lipids are rationally designed and readily synthesized, comprising thymine/cytosine, an ester/amide linker and an oleyl lipid. The diversity of four nucleobase-lipids termed DXBAs (DOTA, DNTA, DOCA and DNCA) is investigated. Besides, DNCA is demonstrated to be an effective neutral transfection material for nucleic acid delivery, which enbles to bind to oligonucleotides via H-bonding and π-π stacking with reduced toxicity in vitro and in vivo...
June 14, 2018: Biomaterials
Shahryar Khoshtinat Nikkhoi, Fatemeh Rahbarizadeh, Davoud Ahmadvand, Seyed Moein Moghimi
The variable domain of the heavy chain antibodies (VHHs) is the smallest (15 kDa) intact single domain antigen-binding fragment. VHHs often exhibit sub-nanomolar affinity for their designated targets and therefore are receiving increasing attention in molecular targeting and nanomedicine engineering. We cloned and expressed four non-overlapping anti-HER2 VHHs in a prokaryotic expression system that yielded periplasmic expression of disulfide-bonded VHHs. Purified VHHs, before and after thiolation, were characterized by Western blot and their functionality against the ecto-domain of HER2 receptor was confirmed by ELISA and flow cytometry...
June 19, 2018: European Journal of Pharmaceutical Sciences
Nebojsa Mihajlica, Christer Betsholtz, Margareta Hammarlund-Udenaes
Pericytes are perivascular cells that play important roles in the regulation of the blood-brain barrier (BBB) properties. Pericyte-deficiency causes compromised BBB integrity and increase in permeability to different macromolecules mainly by upregulated transcytosis. The aim of the present study was to investigate pericyte involvement in the extent of small-molecular drug transport across the BBB. This was performed with five compounds: diazepam, digoxin, levofloxacin, oxycodone and paliperidone. Compounds were administered at low doses via subcutaneous injections as a cassette (simultaneously) to pericyte-deficient Pdgfbret/ret mice and corresponding WT controls...
June 19, 2018: European Journal of Pharmaceutical Sciences
Valentina Di Liberto, R Maarten van Dijk, Matthias Brendel, Ann-Marie Waldron, Christina Möller, Ines Koska, Isabel Seiffert, Fabio Gualtieri, Franz Josef Gildehaus, Barbara von Ungern-Sternberg, Magdalena Lindner, Sibylle Ziegler, Rupert Palme, Rainer Hellweg, Peter Gass, Peter Bartenstein, Heidrun Potschka
Psychiatric comorbidities are prevalent in patients with epilepsy and greatly contribute to the overall burden of disease. The availability of reliable biomarkers to diagnose epilepsy-associated comorbidities would allow for effective treatment and improved disease management. Due to their non-invasive nature, molecular imaging techniques such as positron emission tomography (PET) are ideal tools to measure pathologic changes. In the current study we investigated the potential of [18 F]fluoro-2-deoxy-d-glucose ([18 F]FDG) and 2'-methoxyphenyl-(N-2'-pyridinyl)-p-18 F-fluoro-benzamidoethylpiperazine ([18 F]MPPF) as imaging correlates of neurobehavioral comorbidities in the pilocarpine rat model of epilepsy...
June 19, 2018: Neurobiology of Disease
Vittoria Massafra, Roberto Pellicciari, Antimo Gioiello, Saskia W C van Mil
Bile acids are amphipathic molecules that were previously known to serve as fat solubilizers in the intestine in postprandial conditions. In the last two decades, bile acids have been recognized as signaling molecules regulating energy metabolism pathways via, amongst others, the farnesoid X receptor (FXR). Upon bile acid activation, FXR controls expression of genes involved in bile acid, lipid, glucose and amino acid metabolism. In addition, FXR activation has been shown to limit the inflammatory response...
June 19, 2018: Pharmacology & Therapeutics
Diego A T Pires, Luisa M R Arake, Luciano P Silva, Alejandro Lopez-Castillo, Maura V Prates, Claudia J Nascimento, Carlos Bloch
A previously undescribed six residues long peptide His-Arg-Phe-Leu-Arg-His was identified and purified from the skin secretion of the amphibian Phyllomedusa centralis. A synthetic analogue carboxyamidated HRFLRH-NH2 showed structural changes induced by CO2 and metal ions in aqueous solution when analyzed by NMR. The present work reports NMR structures for the carboxyamidated hexapeptide in the presence CO2 , Zn2+ and Cd2+ , suggesting possible affinity regions on the polypeptide chain for each ligand. The NMR structures were optimized by DFT to identify probable biding sites of these species in the polypeptide structure...
June 19, 2018: Peptides
Lauren M Stein, Christopher J Haddock, Willis K Samson, Grant R Kolar, Gina L C Yosten
Using a series of classical protein purification techniques, coupled with more modern molecular approaches, a family of neuropeptides, the Phoenixins, were identified to be produced in brain and heart, and to bind selectively in pituitary gland, ovary and brain. These same binding sites were revealed, using a novel receptor identification strategy, to express the orphan G protein-coupled receptor, GPR173, the expression of which was required for the actions of phoenixin both in vivo and in vitro. In fact, studies using small interfering RNA molecules to compromise GPR173 expression revealed the physiologic relevance of the initially reported pharmacologic actions of the peptides...
June 19, 2018: Peptides
Patrick H Kee, Delia Danila
Management of patients suffering from myocardial infarction (MI) is based on the extent of coronary artery disease and myocardial scar burden. We have developed a potentially clinically-useful X-ray molecular imaging contrast agent based on gold nanoparticle (AuNPs) functionalized with collagen-binding adhesion protein 35 (CNA35) with the capabilities of achieving prolonged blood pool enhancement for vascular imaging of the coronary arteries and specific targeting of collagen within myocardial scar. At a concentration of ~ 45mg Au/ml, AuNPs maintained a stable blood pool enhancement at 142-160 HU within an hour of intravenous administration...
June 19, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
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