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double fold

Lingci Zhao, Irina P Suarez, Diego F Gauto, Rodolfo M Rasia, Jin Wang
The intrinsically disordered protein domain DCL1-A is the first report of a complete double stranded RNA binding domain folding upon binding. DCL1-A recognizes the dsRNA by acquiring a well-folded structure after engagement with its interaction partner. Despite the structural characterization of the interaction complex underlying the recognition of dsRNA has been established, the dynamics of disorder-to-order transitions in the binding process remains elusive. Here we have developed a coarse-grained structure-based model with consideration of electrostatic interactions to explore the mechanism of the coupled folding and binding...
March 22, 2018: Physical Chemistry Chemical Physics: PCCP
Luís A B Tonaco, Flavia L Gomes, Gustavo Velasquez-Melendez, Miriam T P Lopes, Carlos E Salas
INTRODUCTION: The aim of the study was to investigate the role of the proteolytic fraction from Vasconcellea cundinamarcensis, designated as P1G10, on the healing of chronic foot ulcers in neuropathic patients with diabetes 2. METHODS: Fifty patients were enrolled in a prospective, randomized, double-blind trial, to verify the efficacy and safety of a topical dressing formulated with 0.1% P1G10, intended for wound healing, versus a hydrogel (control) protocol. Upon completion of the intervention, the outcome evaluated the number of patients attaining full epithelization (100%), or at least 80% healing...
March 21, 2018: Advances in Therapy
Mateja Hajdinjak, Qiaomei Fu, Alexander Hübner, Martin Petr, Fabrizio Mafessoni, Steffi Grote, Pontus Skoglund, Vagheesh Narasimham, Hélène Rougier, Isabelle Crevecoeur, Patrick Semal, Marie Soressi, Sahra Talamo, Jean-Jacques Hublin, Ivan Gušić, Željko Kućan, Pavao Rudan, Liubov V Golovanova, Vladimir B Doronichev, Cosimo Posth, Johannes Krause, Petra Korlević, Sarah Nagel, Birgit Nickel, Montgomery Slatkin, Nick Patterson, David Reich, Kay Prüfer, Matthias Meyer, Svante Pääbo, Janet Kelso
Although it has previously been shown that Neanderthals contributed DNA to modern humans, not much is known about the genetic diversity of Neanderthals or the relationship between late Neanderthal populations at the time at which their last interactions with early modern humans occurred and before they eventually disappeared. Our ability to retrieve DNA from a larger number of Neanderthal individuals has been limited by poor preservation of endogenous DNA and contamination of Neanderthal skeletal remains by large amounts of microbial and present-day human DNA...
March 21, 2018: Nature
Taukeer A Khan, Torsten Fornefeld, Dennis Hübner, Philipp Vana, Lutz F Tietze
A palladium-catalyzed 4-fold domino reaction consisting of two carbopalladation reactions and two C-H activation reactions, followed by the introduction of an acrylate moiety, led to the tetra-substituted helical alkene A2, using the dialkyne A3 as a substrate. The alkene was copolymerized with butyl acrylate by using the reversible addition-fragmentation chain transfer polymerization (RAFT) to give the desired polymeric switch A1.
March 20, 2018: Organic Letters
Tsuyoshi Yamamoto, Ken Hoshikawa, Kentaro Ezura, Risa Okazawa, Satoshi Fujita, Miyo Takaoka, Hugh S Mason, Hiroshi Ezura, Kenji Miura
An efficient and high yielding expression system is required to produce recombinant proteins. Furthermore, the transient expression system can be used to identify the localization of proteins in plant cells. In this study, we demonstrated that combination of a geminiviral replication and a double terminator dramatically enhanced the transient protein expression level in plants. The GFP protein was expressed transiently in lettuce, Nicotiana benthamiana, tomatoes, eggplants, hot peppers, melons, and orchids with agroinfiltration...
March 19, 2018: Scientific Reports
Ruifu Yang, Mingwu Zhou, Chaofeng Xing, Shimin Li, Li Song, Jia Chen, Yingjie Xiong, Kai Zhang
Objective: To expound the clinical effect of a new operation by transplanting double segment triangular fibula flap with vascular pedicle to repair the forefoot with lateral bone defect, and to study how to improve the operation method in the following stage. Methods: The inclusion criteria: More than 2 phalangeal and metatarsal bones defects of the lateral forefoot, widespread skin and soft tissue defects on pelma and dorsal foot, and destruction of the anterior aspect of foot arch, which seriously affects the foot function...
December 2017: Saudi Journal of Biological Sciences
Hung-Chih Yang, Hsiao-Hui Tsou, Sung-Nan Pei, Cheng-Shyong Chang, Jia-Hong Chen, Ming Yao, Shyh-Jer Lin, Johnson Lin, Quan Yuan, Ningshao Xia, Tsang-Wu Liu, Pei-Jer Chen, Ann-Lii Cheng, Chiun Hsu
BACKGROUND AND AIMS: Absence or low anti-hepatitis B (HBV) surface antibody (anti-HBs) is associated with increased risk of HBV reactivation in lymphoma patients with resolved HBV infection receiving rituximab-containing chemotherapy. Quantification of anti-HBV core antibody (anti-HBc) is a new marker associated with the natural history and treatment response of chronic HBV infection. This study investigated whether baseline anti-HBc and anti-HBs levels may better predict HBV reactivation...
March 15, 2018: Journal of Hepatology
Xinwei Ge, Yunxiang Sun, Feng Ding
Accumulating evidence suggests that soluble oligomers are more toxic than final fibrils of amyloid aggregations. Among the mixture of inter-converting intermediates with continuous distribution of sizes and secondary structures, oligomers in the β-barrel conformation - a common class of protein folds with a closed β-sheet - have been postulated as the toxic species with well-defined three-dimensional structures to perform pathological functions. A common mechanism for amyloid toxicity, therefore, implies that all amyloid peptides should be able to form β-barrel oligomers as the aggregation intermediates...
March 14, 2018: Biochimica et Biophysica Acta
Smita Das, Roger B Peck, Rebecca Barney, Ihn Kyung Jang, Maria Kahn, Meilin Zhu, Gonzalo J Domingo
BACKGROUND: As malaria endemic countries shift from control to elimination, the proportion of low density Plasmodium falciparum infections increases. Current field diagnostic tools, such as microscopy and rapid diagnostic tests (RDT), with detection limits of approximately 100-200 parasites/µL (p/µL) and 800-1000 pg/mL histidine-rich protein 2 (HRP2), respectively, are unable to detect these infections. A novel ultra-sensitive HRP2-based Alere™ Malaria Ag P.f RDT (uRDT) was evaluated in laboratory conditions to define the test's performance against recombinant HRP2 and native cultured parasites...
March 17, 2018: Malaria Journal
Hyuck Hur, Richard J Reeder
Sorption of tungstate on boehmite (γ-AlOOH) is increased by co-sorption with Co2+ over the near-neutral pH range. Batch uptake experiments show up to a 3-fold increase in tungstate uptake over the range WO4 2- =50-1000μmol/L compared to boehmite not treated with Co2+ . Desorption experiments reveal a corresponding decrease in sorption reversibility for tungstate co-sorbed with Co2+ . Reaction of boehmite with Co2+ results in the formation of CoAl layered double hydroxide (LDH), as confirmed by X-ray diffraction and X-ray absorption spectroscopy...
March 2018: Journal of Environmental Sciences (China)
Dorothy W Gietzen, Sarah H Lindström, James W Sharp, Pok Swee Teh, Michael J Donovan
Background: Low protein amounts are used in ketogenic diets (KDs), where an essential (indispensable) amino acid (IAA) can become limiting. Because the chemically sensitive, seizurogenic, anterior piriform cortex (APC) is excited by IAA limitation, an imbalanced KD could exacerbate seizure activity. Objective: We questioned whether dietary IAA depletion worsens seizure activity in rodents fed KDs. Methods: In a series of 6 trials, male rats or gerbils of both sexes (6-8/group) were given either control diets (CDs) appropriate for each trial, a KD, or a threonine-devoid (ThrDev) diet for ≥7 d, and tested for seizures using various stimuli...
March 1, 2018: Journal of Nutrition
Hernan Garcia-Ruiz, Arturo Diaz, Paul Ahlquist
Positive-strand RNA viruses replicate their genomes in membrane-bound replication compartments. Brome mosaic virus (BMV) replicates in vesicular invaginations of the endoplasmic reticulum membrane. BMV has served as a productive model system to study processes like virus-host interactions, RNA replication and recombination. Here we present multiple lines of evidence showing that the structure of the viral RNA replication compartments plays a fundamental role and that recruitment of parental RNAs to a common replication compartment is a limiting step in intermolecular RNA recombination...
March 15, 2018: Viruses
Verònica Gálvez, Adrienne Li, Christina Huggins, Paul Glue, Donel Martin, Andrew A Somogyi, Angelo Alonzo, Anthony Rodgers, Philip B Mitchell, Colleen K Loo
BACKGROUND: Ketamine research in depression has mostly used intravenous, weight-based approaches, which are difficult to translate clinically. Intranasal (IN) ketamine is a promising alternative but no controlled data has been published on the feasibility, safety and potential efficacy of repeated IN ketamine treatments. METHODS: This randomised, double-blind, placebo-controlled pilot study compared a 4-week course of eight treatments of 100 mg ketamine or 4.5 mg midazolam...
March 1, 2018: Journal of Psychopharmacology
Jarkko Mäntylä, Tuuli Thomander, Auli Hakulinen, Kaarina Kukkonen, Kati Palosuo, Helena Voutilainen, Anna Pelkonen, Paula Kauppi
INTRODUCTION: The standard care of severe food allergy in both adults and children means avoidance of allergens. In recent years promising results of oral immunotherapy (OIT) have been reported in children. In adults, information on OIT in severe food allergy is very limited. OBJECTIVE: We aimed to study if OIT is possible in adults. METHODS: We report OIT results in 10 adult patients with milk OIT, nine adult patients with peanut OIT, and four adult patients with egg OIT...
March 15, 2018: Immunity, Inflammation and Disease
Cody Caba, Hyder Ali Khan, Janeen Auld, Ryo Ushioda, Kazutaka Araki, Kazuhiro Nagata, Bulent Mutus
Despite its study since the 1960's, very little is known about the post-translational regulation of the multiple catalytic activities performed by protein disulfide isomerase (PDI), the primary protein folding catalyst of the cell. This work identifies a functional role for the highly conserved CxxC-flanking residues Lys57 and Lys401 of human PDI in vitro . Mutagenesis studies have revealed these residues as modulating the oxidoreductase activity of PDI in a pH-dependent manner. Non-conservative amino acid substitutions resulted in enzyme variants upwards of 7-fold less efficient...
2018: Frontiers in Molecular Biosciences
Raynell Lang, Ron Read, Hartmut B Krentz, Soheil Ramazani, Mingkai Peng, Jennifer Gratrix, M John Gill
BACKGROUND: Syphilis is a global health concern disproportionately affecting HIV-infected populations. In Alberta, Canada, the incidence of syphilis in the general population has recently doubled with 25% of these infections occurring in HIV-infected patients. The Southern Alberta HIV Clinic (SAC) and Calgary STI Program (CSTI) analyzed the epidemiologic characteristics of incident syphilis infections in our well-defined, HIV-infected population over 11 years. METHODS: Since 2006, as routine practice of both the Southern Alberta Clinic (SAC) and Calgary STI Programs (CSTI), syphilis screening has accompanied HIV viral load measures every four months...
March 13, 2018: BMC Infectious Diseases
Ami R Zota, Ruth J Geller, Laura E Romano, Kimberly Coleman-Phox, Nancy E Adler, Emily Parry, Miaomiao Wang, June-Soo Park, Angelo F Elmi, Barbara A Laraia, Elissa S Epel
BACKGROUND: Endocrine-disrupting chemicals (EDCs) can target immune and metabolic pathways. However, few epidemiologic studies have examined the influence of EDCs on measures of inflammation and cellular aging during pregnancy and postpartum. OBJECTIVE: We investigated associations between prenatal exposures to polybrominated diphenyl ethers (PBDEs), hydroxylated PBDE metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and per- and polyfluorochemicals (PFASs) with repeated biomarker measurements of inflammation and cellular aging in women during pregnancy and the postpartum period...
March 10, 2018: Environment International
Charlotte H Maden, David Fairman, Michelle Chalker, Maria J Costa, William A Fahy, Nadia Garman, Pauline T Lukey, Tim Mant, Simon Parry, Juliet K Simpson, Robert J Slack, Stuart Kendrick, Richard P Marshall
PURPOSE: Inhaled drug delivery is an attractive route by which to deliver drugs to lungs of patients with idiopathic pulmonary fibrosis (IPF). GSK3008348 is a potent and selective small molecule being developed as the first inhaled inhibitor of the αvβ6 integrin for the treatment of IPF. The phase 1 first-time-in-human clinical trial (NCT02612051) presented here was designed to investigate the safety, tolerability and pharmacokinetic (PK) profile of single doses of GSK3008348 in healthy participants...
March 12, 2018: European Journal of Clinical Pharmacology
Chenlang Liu, Fangnan Yu, Qingshu Liu, Xiaoying Bian, Shengbiao Hu, Huansheng Yang, Yulong Yin, Yuezhong Li, Yuemao Shen, Liqiu Xia, Qiang Tu, Youming Zhang
Transporter engineering has been shown to be a positive approach for enhancing natural product titers in microbial cell factories by expelling target compounds out of feasible hosts. In this work, two multidrug efflux pumps, Orf14 and Orf3, were modulated in the epothilone production strain Burkholderia DSM7029::Tn5-km-epo (named G32) via Red/ET engineering to increase heterologous polyketide epothilone yields. Compared with the prior G32 strain, the total production of several epothilones in the G32::orf14-orf3 mutant was meaningfully doubled according to high-performance liquid chromatography-mass spectrometer (HPLC-MS) analysis...
February 26, 2018: FEMS Microbiology Letters
Michael M Farag, Nevine S Abd El Malak, Soad A Yehia
The aim of this study was to develop a novel buccal bi-layered chronopatch capable of eliciting pulsatile release pattern of drugs treating diseases with circadian rhythm related manifestation. Zaleplon (ZLP) was used as a model drug intended to induce sleep and to treat middle of night insomnia. The chronopatch was prepared adopting double casting technique. The first layer was composed of a controlled release patch containing ZLP-Precirol melt granules intended to release ZLP in a sustained manner to maintain sleep and to prevent early morning awakening...
March 8, 2018: International Journal of Pharmaceutics
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