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Andrea Saponaro, Francesca Cantini, Alessandro Porro, Annalisa Bucchi, Dario DiFrancesco, Vincenzo Maione, Chiara Donadoni, Bianca Introini, Pietro Mesirca, Matteo Elia Mangoni, Gerhard Thiel, Lucia Banci, Bina Santoro, Anna Moroni
Binding of TRIP8b to the cyclic nucleotide binding domain (CNBD) of mammalian HCN channels prevents their regulation by cAMP. Since TRIP8b is expressed exclusively in the brain, we envisage that it can be used for orthogonal control of HCN channels beyond the central nervous system. To this end, we have identified by rational design a 40-aa long peptide (TRIP8bnano ) that recapitulates affinity and gating effects of TRIP8b in HCN isoforms (human hHCN1, mHCn2, rbHCN4) and in the cardiac current If in rabbit and mouse sinoatrial node cardiomyocytes...
June 20, 2018: ELife
Rachel Wodarski, Deniz Bagdas, Jason J Paris, Tim Pheby, Wisam Toma, Ruqiang Xu, M Imad Damaj, Pamela E Knapp, Andrew S C Rice, Kurt F Hauser
Introduction: HIV infection is associated with chronic pain states, including sensory neuropathy, which affects greater than 40% of patients. Objectives and Methods: To determine the impact of HIV-Tat induction on nociceptive behaviour in female mice conditionally expressing HIV Tat1-86 protein through a doxycycline (DOX)-driven glial fibrillary acidic protein promoter, intraepidermal nerve fibre density and immune cell activation in the dorsal root ganglion (DRG) and spinal cord were assessed by immunohistochemistry...
May 2018: Pain Reports (Baltimore, Md.)
Toan Thanh Thi Do, Mai Dinh Le, Thanh Van Nguyen, Bach Xuan Tran, Huong Thi Le, Hinh Duc Nguyen, Long Hoang Nguyen, Cuong Tat Nguyen, Tho Dinh Tran, Carl A Latkin, Roger C M Ho, Melvyn W B Zhang
BACKGROUND: As smartphone becomes increasingly prevalent and affordable, more youths today can own a smartphone device and download applications in various application stores. Smartphone applications have been proven to be useful for youths in various aspects. However, there has been a paucity of data looking into the preferences of Vietnamese youths and adolescents with regards to health-related applications and their receptiveness towards smartphone apps. Therefore, this study aimed to determine the receptiveness and preferences of health-related smartphone applications (mHealth apps) among online Vietnamese youths and adolescents...
June 19, 2018: BMC Public Health
Diane E Milenic, Young-Seung Kim, Kwamena E Baidoo, Karen J Wong, Rachel Barkley, Jose Delgado, Martin W Brechbiel
Refinement of treatment regimens enlisting targeted α-radiation therapy (TAT) is an ongoing effort. Among the variables to consider are the target molecule, radionuclide, dosage, and administration route. The panitumumab F(ab')2 fragment targeting epidermal growth factor receptor tolerated modification with the TCMC chelate as well as radiolabeling with 203 Pb or 212 Pb. Good specific activity was attained when the immunoconjugate was labeled with 212 Pb (9.6 ± 1.4 mCi/mg). Targeting of LS-174T tumor xenografts with the 203 Pb-panitumumab F(ab')2 demonstrated comparable amounts of uptake to the similarly radiolabeled panitumumab IgG...
June 2018: Cancer Biotherapy & Radiopharmaceuticals
Yukiko Hasuike, Naoto Kakita, Makoto Aichi, Satoko Masachika, Mari Kantou, Shoko Ikeda Takahashi, Masayoshi Nanami, Yasuyuki Nagasawa, Takahiro Kuragano, Takeshi Nakanishi
OBJECTIVE: For patients with end-stage renal disease on hemodialysis, the durability of vascular access (VA) is still far from optimal, and access survival after intervention for access failure is an important aspect. Procoagulant status is a leading cause of access failure. Coagulation-fibrinolysis imbalance can occur in hemodialyzed patients, but the influence of the imbalance has not been fully elucidated. METHODS: We prospectively examined coagulation-fibrinolysis balance to assess the risk of access failure after the intervention of revascularization in a cohort of 462 hemodialysis patients...
June 15, 2018: Journal of Vascular Surgery
Andrea F Auletta, Simone Cupellaro, Luigi Abbate, Elena Aiello, Pamela Cornacchia, Claudia Norcia, Carla Sogos
Previous research has shown that stimulus pull is one of the contributory factors influencing Thematic Apperception Test (TAT) responses. In recent years, there has been a resurgence of studies examining this. In particular, the Social Cognition and Object Relations Scale-Global Rating Method (SCORS-G) has been employed to examine stimulus pull in adult clinical and nonclinical samples. The present study is the first attempt to examine this issue in a nonclinical sample of children. Ninety-eight children from Italian elementary (1st to 5th grade) and middle (6th to 8th grade) schools provided narratives to six TAT cards (1, 2, 3BM, 4, 8BM, and 16)...
June 1, 2018: Assessment
Rui Ran, Haofei Wang, Yun Liu, Yue Hui, Qi Sun, Arjun Seth, David Wibowo, Dong Chen, Chun-Xia Zhao
Precise engineering of nanoparticles with systematically varied properties (size, charge surface properties, targeting ligands, etc.) remains a challenge, limiting the effective optimization of nanoparticles for particular applications. Herein we report a single-step microfluidic combinatorial approach for producing a library of single and dual-ligand liposomes with systematically-varied properties including size, zeta potential, targeting ligand, ligand density, and ligand ratio. A targeting ligand folic acid and a cell penetrating peptide TAT were employed to achieve the optimal synergistic targeting effect...
June 14, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Hanjun Zhao, Kelvin K W To, Hin Chu, Qiulu Ding, Xiaoyu Zhao, Cun Li, Huiping Shuai, Shuofeng Yuan, Jie Zhou, Kin-Hang Kok, Shibo Jiang, Kwok-Yung Yuen
Limited efficacy of current antivirals and antiviral-resistant mutations impairs anti-influenza treatment. Here, we evaluate the in vitro and in vivo antiviral effect of three defective interfering genes (DIG-3) of influenza virus. Viral replication is significantly reduced in cell lines transfected with DIG-3. Mice treated with DIG-3 encoded by jetPEI-vector, as prophylaxis and therapeutics against A(H7N7) virus, respectively, have significantly better survivals (80% and 50%) than control mice (0%). We further develop a dual-functional peptide TAT-P1, which delivers DIG-3 with high efficiency and concomitantly exerts antiviral activity by preventing endosomal acidification...
June 15, 2018: Nature Communications
Xiaoling Chen, Luyao Zhang, Yue Wu, Lei Wang, Chengbang Ma, Xinping Xi, Olaf R P Bininda-Emonds, Chris Shaw, Tianbao Chen, Mei Zhou
Mastoparan is a typical cationic and amphipathic tetradecapeptide found in wasp venom and exhibits potent biological activities. Yet, compared with other insect-derived peptides, such as melittin from the bee venom, this family have been underrated. Herein, we evaluated the biological activities of mastoparan-C (MP-C), which was identified from the venom of the European Hornet ( Vespa crabro ), and rationally designed two analogues (a skeleton-based cyclization by two cysteine residues and an N-terminal extension via tat-linked) for enhancing the stability of the biological activity and membrane permeability, respectively...
2018: International Journal of Biological Sciences
Kyle M Ewart, Greta J Frankham, Ross McEwing, Dang Tat The, Carolyn J Hogg, Claire Wade, Nathan Lo, Rebecca N Johnson
Rhinoceros (rhinos) have suffered a dramatic increase in poaching over the past decade due to the growing demand for rhino horn products in Asia. One way to reverse this trend is to enhance enforcement and intelligence gathering tools used for species identification of horns, in particular making them fast, inexpensive and accurate. Traditionally, species identification tests are based on DNA sequence data, which, depending on laboratory resources, can be either time or cost prohibitive. This study presents a rapid rhino species identification test, utilizing species-specific primers within the cytochrome b gene multiplexed in a single reaction, with a presumptive species identification based on the length of the resultant amplicon...
2018: PloS One
José R Valverde, Sonia Gullón, Rafael P Mellado
BACKGROUND: Streptomyces lividans has demonstrated its value as an efficient host for protein production due to its ability to secrete functional proteins directly to the media. Secretory proteins that use the major Sec route need to be properly folded outside the cell, whereas secretory proteins using the Tat route appear outside the cell correctly folded. This feature makes the Tat system very attractive for the production of natural or engineered Tat secretory proteins. S. lividans cells are known to respond differently to overproduction and secretion of Tat versus Sec proteins...
June 14, 2018: BMC Microbiology
Shruthi Hamsanathan, Siegfried M Musser
The Tat machinery catalyzes the transport of folded proteins across the cytoplasmic membrane in bacteria and the thylakoid membrane in plants. Transport occurs only in the presence of an electric field (Δψ) and/or a pH (ΔpH) gradient, and thus, Tat transport is considered to be dependent on the proton motive force (pmf). This presents a fundamental and major challenge, namely, that the Tat system catalyzes the movement of large folded protein cargos across a membrane without collapse of ion gradients. Current models argue that the active translocon assembles de novo for each cargo transported, thus providing an effective gating mechanism to minimize ion leakage...
June 1, 2018: FEMS Microbiology Letters
Emmanouil Papasavvas, Steven M Lada, Jocelin Joseph, Xiangfan Yin, Qin Liu, Livio Azzoni, Karam Mounzer, Jay R Kostman, Douglas Richman, Luis J Montaner
OBJECTIVE: The impact of short-term analytical antiretroviral therapy (ART) interruptions on the levels of cellular HIV and of residual activation after subsequent ART-mediated plasma HIV viral load re-suppression remains under active investigation. DESIGN: Peripheral blood mononuclear cells (PBMC) from 23 ART-suppressed, chronically HIV-1-infected subjects were evaluated at the initiation of an analytical treatment interruption (ATI), during ATI, and following plasma re-suppression of HIV with ART...
June 11, 2018: AIDS
Na Li, Qiaoqiao Sun, Zhengze Yu, Xiaonan Gao, Wei Pan, Xiuyan Wan, Bo Tang
Clinical cancer treatments nowadays still face the challenge of recurrence due to the residual cancer cells and minute lesions in surgeries or chemotherapies. To effectively address the problem, we introduce a strategy for constructing cancer cell nuclear-targeted copper sulfide nanoparticles (NPs) with significant photothermal effect to completely kill residual cancer cells and prevent local cancer recurrence. The NPs could directly target to the tumor cells and further enter the nucleus by the surface modification of RGD and TAT peptides...
June 12, 2018: ACS Nano
Shu-Yu Fang, Jie-Jie Cui, Meng-Jia Gong, Yun He, Jing-Fang Zhang, Yang Bi
OBJECTIVE: To investigate the effects of different concentrations of all-trans retinoic acid (ATRA) on the maturation, differentiation and autophagy of Hepa1-6 cells. MONTHOD: Hepa1-6 cells were treated with 0.1, 1, and 10 µmol/L ATRA, and the changes in the expressions of hepatic specific markers were detected using real-time PCR and Western blotting. Indocyanine green (ICG) and periodic acid-schiff (PAS) staining was used to assess the functional maturation of Hepa1-6 cells, and the cell-cell junction and autophagy were observed under transmission electron microscopy to determine the optimal concentration of ATRA for treatment...
May 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
George Awungafac, Elvis T Amin, Akemfua Fualefac, Noah F Takah, Lucy A Agyingi, Julius Nwobegahay, Pascale Ondoa, Patrick A Njukeng
BACKGROUND: The viral load (VL) in patients receiving antiretroviral therapy (ART) is the best predictor of treatment outcome. The anticipated benefits of VL monitoring depend on the actual uptake of VL test results for clinical decisions. The objective of this study was to assess the uptake and utilization of VL test results for clinical decisions on HIV treatment in Cameroon, from 2013 to 2017. METHODS: This was a retrospective cohort analysis of data from files of patients receiving ART at Buea, Limbe, Bamenda and Bafoussam regional hospital HIV treatment centers...
2018: PloS One
Nikki A Thiele, Justin J Wilson
The α-emitting radionuclide actinium-225 possesses nuclear properties that are highly promising for use in targeted α therapy (TAT), a therapeutic strategy that employs α particle emissions to destroy tumors. A key factor, however, that may hinder the clinical use of actinium-225 is the poor understanding of its coordination chemistry, which creates challenges for the development of suitable chelation strategies for this ion. In this article, we provide an overview of the known chemistry of actinium and a summary of the chelating agents that have been explored for use in actinium-225-based TAT...
June 11, 2018: Cancer Biotherapy & Radiopharmaceuticals
Ka-Him Chun, Hua Zhang, Wing-Tat Chan
Double-viewing-position single-particle inductively coupled plasma-atomic emission spectrometry (DVP-SP-ICP-AES) measures emission intensity at two ICP vertical positions simultaneously using a single photomultiplier tube. A particle travelling up the ICP gives two consecutive temporal emission peaks. The Yb II 328.937-nm emission intensity of the two peaks for single Yb2 O3 particles of diameter of 200 - 2000 nm are plotted against each other in a correlation plot. The correlation is poor when the gas temperature at the lower observation position is approximately the boiling point of the particles...
2018: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
Christophe Chopard, Phuoc Bao Viet Tong, Petra Tóth, Malvina Schatz, Hocine Yezid, Solène Debaisieux, Clément Mettling, Antoine Gross, Martine Pugnière, Annie Tu, Jean-Marc Strub, Jean-Michel Mesnard, Nicolas Vitale, Bruno Beaumelle
Most HIV-1 Tat is unconventionally secreted by infected cells following Tat interaction with phosphatidylinositol (4,5) bisphosphate (PI(4,5)P2 ) at the plasma membrane. Extracellular Tat is endocytosed by uninfected cells before escaping from endosomes to reach the cytosol and bind PI(4,5)P2 . It is not clear whether and how incoming Tat concentrates in uninfected cells. Here we show that, in uninfected cells, the S-acyl transferase DHHC-20 together with the prolylisomerases cyclophilin A (CypA) and FKBP12 palmitoylate Tat on Cys31 thereby increasing Tat affinity for PI(4,5)P2 ...
June 8, 2018: Nature Communications
Gabriele Andrea Lugli, Walter Mancino, Christian Milani, Sabrina Duranti, Francesca Turroni, Douwe van Sinderen, Marco Ventura
The repertoire of secreted proteins decoded by a microorganism represents proteins released from or associated with the cell's surface. In gut commensals, such as bifidobacteria, these proteins are perceived to be functionally relevant as they regulate the interaction with the gut environment. In the current study, we have screened the predicted proteome of over 300 bifidobacterial strains amongst the currently recognized bifidobacterial species to generate a comprehensive database encompassing bifidobacterial extracellular proteins...
June 8, 2018: Applied and Environmental Microbiology
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