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Aida Llauró, Pablo Guerra, Ravi Kant, Brian Bothner, Núria Verdaguer, Pedro J de Pablo
Vault particles are naturally occurring proteinaceous cages with promising application as molecular containers. The use of vaults as functional transporters requires a profound understanding of their structural stability to guarantee the protection and controlled payload delivery. Previous results performed with bulk techniques or at non-physiological conditions have suggested pH as a parameter to control vault dynamics. Here we use Atomic Force Microscopy (AFM) to monitor the structural evolution of individual vault particles while changing the pH in real time...
October 14, 2016: Scientific Reports
Noriaki Nagai
 The ophthalmic application of drugs is the primary route of administration for the therapy of glaucoma; however, in traditional formulations, only small amounts of the administered drug penetrate the cornea to reach the desired intraocular tissue due to corneal barriers. Recently, nanoparticulate drug delivery is expected as a technology to overcome the difficulties in delivering drugs across biological barriers (improvement of bioavailability). In this study, we attempted to establish a new method for preparing solid drug nanoparticles by using a bead mill and various additives, and succeeded in preparing a high quality dispersion containing drug nanoparticles...
2016: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Miguel Ángel Muñoz-Ruiz, Anette Hall, Jussi Mattila, Juha Koikkalainen, Sanna-Kaisa Herukka, Minna Husso, Tuomo Hänninen, Ritva Vanninen, Yawu Liu, Merja Hallikainen, Jyrki Lötjönen, Anne M Remes, Irina Alafuzoff, Hilkka Soininen, Päivi Hartikainen
BACKGROUND: Disease State Index (DSI) and its visualization, Disease State Fingerprint (DSF), form a computer-assisted clinical decision making tool that combines patient data and compares them with cases with known outcomes. AIMS: To investigate the ability of the DSI to diagnose frontotemporal dementia (FTD) and Alzheimer's disease (AD). METHODS: The study cohort consisted of 38 patients with FTD, 57 with AD and 22 controls. Autopsy verification of FTD with TDP-43 positive pathology was available for 14 and AD pathology for 12 cases...
May 2016: Dementia and Geriatric Cognitive Disorders Extra
Youssef M Mosaad, Rasha Elashery, Ahmad Darwish, Omar A Sharaf Eldein, Tarek Barakat, Samy Marouf, Noha T Abou El-Khier, Laila F Youssef, Iman M Fawzy
To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = ...
August 9, 2016: Leukemia & Lymphoma
J Maxwell Dow
Cell-to-cell signals of the Diffusible Signal Factor (DSF) family are cis-2-unsaturated fatty acids of differing chain length and branching pattern. DSF signalling has been described in diverse bacteria to include plant and human pathogens where it acts to regulate functions such as biofilm formation, antibiotic tolerance and the production of virulence factors. DSF family signals can also participate in interspecies signalling with other bacteria and interkingdom signaling such as with the yeast Candida albicans...
September 29, 2016: Journal of Applied Microbiology
Annabel O Franz, Tiffany M Harrop, David M McCord
This study aimed to examine the construct validity of the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) interpersonal functioning scales (Ben-Porath & Tellegen, 2008/2011 ) using as a criterion measure the Computerized Adaptive Test of Personality Disorder-Static Form (CAT-PD-SF; Simms et al., 2011 ). Participants were college students (n = 98) recruited through the university subject pool. A series of a priori hypotheses were developed for each of the 6 interpersonal functioning scales of the MMPI-2-RF, expressed as predicted correlations with construct-relevant CAT-PD-SF scales...
September 23, 2016: Journal of Personality Assessment
Kaku Goto, Naoya Kato, Raymond T Chung
We recently described that the anti-apoptotic AMPK-related kinase, SNARK, promotes transforming growth factor (TGF)-β signaling in hepatocellular carcinoma (HCC) cells, as a potentially new therapeutic target. Here we explored FDA-approved drugs inhibiting the enzymatic activity of SNARK, using an in vitro luminescence kinase assay system. Interestingly, the long-used anti-alcoholism drug disulfiram (DSF), also known as Antabuse, emerged as the top hit. Enzymatic kinetics analyses revealed that DSF inhibited SNARK kinase activity in a noncompetitive manner to ATP or phosphosubstrates...
September 2, 2016: Oncotarget
Yong-Hong Yu, Zhe Hu, Hui-Juan Dong, Jin-Cheng Ma, Hai-Hong Wang
Xanthomonas campestris pv. campestris (Xcc), a Gram-negative phytopathogenic bacterium, causes black rot disease of cruciferous vegetables. Although Xcc has a complex fatty acid profile comprised of straight-chain fatty acids and branched-chain fatty acids (BCFAs), and encodes a complete set of genes required for fatty acid synthesis, there is still little known about the mechanism of BCFA synthesis. We reported that expression of Xcc fabH restores the growth of Ralstonia solanacearum fabH mutant, and this allows the R...
2016: Scientific Reports
Xinwei Liu, Lihui Wang, Wei Cui, Xiangzhong Yuan, Lulu Lin, Qi Cao, Nannan Wang, Yi Li, Wei Guo, Xun Zhang, Chunfu Wu, Jingyu Yang
The existence of cancer stem cells (CSCs) in non-small cell lung cancer (NSCLC) has profound implications for cancer therapy. In this study, a disulfiram/copper (DSF/Cu) complex was evaluated in vitro and in vivo for its efficacy to inhibit CSCs, which drive recurrence of NSCLC. First, we investigated whether DSF/Cu could inhibit ALDH-positive NSCLC stem cells in vitro and tumors derived from sorted ALDH-positive CSCs in vivo. DSF/Cu (0.5/1 μmol/l) significantly inhibited the expression of stem cell transcription factors (Sox2, Oct-4 and Nanog) and reduced the capacities of NSCLC stem cells for self-renewal, proliferation and invasion in vitro...
August 16, 2016: Oncotarget
Jifeng Zhang, Vadim Frey, Marta Corcoran, Jian Zhang-van Enk, J Anand Subramony
Thermal stability of the CH2 domain for an IgG1 monoclonal antibody and its aggregation kinetics were systematically studied at pH 4.8, below its pI of 8.8 in individual solutions of arginine salts with acetate, glutamate (Glu(-)), chloride, and sulfate as the anion, in comparison to sodium chloride and sodium sulfate. Thermal unfolding temperature, Tm, an indicator of thermal stability, was measured by both differential scanning calorimetry (DSC) and differential scanning fluorimetry (DSF). The aggregation kinetics was determined by assessing reversibility for the CH2 domain in the DSC repetitive scans and then cross-examined by the isothermal aggregation study measured by size exclusion chromatography...
October 3, 2016: Molecular Pharmaceutics
David Foxe, Cristian E Leyton, John R Hodges, James R Burrell, Muireann Irish, Olivier Piguet
INTRODUCTION: Logopenic progressive aphasia (lv-PPA) is a form of primary progressive aphasia and is predominantly associated with Alzheimer's disease (AD) pathology. The neuropsychological profiles of lv-PPA and typical clinical AD are, however, distinct. In particular, these two syndromes differ on attention span measures, where auditory attention span is more impaired in lv-PPA than in AD and visuospatial span appears more impaired in AD than in lv-PPA. The neural basis of these span profiles, however, remains unclear...
October 2016: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
Zhiqiang Chen, Chao Huang, Naresh Chennamsetty, Xuankuo Xu, Zheng Jian Li
Cation-exchange chromatography (CEX) of a structurally unstable Fc-fusion protein exhibited multi-peak elution profile upon a salt-step elution due to protein aggregation during intra-column buffer transition where low pH and high salt coexisted. The protein exhibited a single-peak elution behavior during a pH-step elution; nevertheless, the levels of soluble aggregates (i.e. high molecular weight species, HMW) in the CEX eluate were still found up to 12-fold higher than that for the load material. The amount of the aggregates formed upon the pH-step elution was dependent on column loading with maximum HMW achieved at intermediate loading levels, supporting the hypothesis that the aggregation was the result of both the conformational changes of the bound protein and the solution concentration of the aggregation-susceptible proteins during elution...
August 19, 2016: Journal of Chromatography. A
Dominic P Byrne, Matthias Vonderach, Samantha Ferries, Philip J Brownridge, Claire E Eyers, Patrick A Eyers
cAMP-dependent protein kinase (PKA) is an archetypal biological signaling module and a model for understanding the regulation of protein kinases. In the present study, we combine biochemistry with differential scanning fluorimetry (DSF) and ion mobility-mass spectrometry (IM-MS) to evaluate effects of phosphorylation and structure on the ligand binding, dynamics and stability of components of heteromeric PKA protein complexes in vitro We uncover dynamic, conformationally distinct populations of the PKA catalytic subunit with distinct structural stability and susceptibility to the physiological protein inhibitor PKI...
October 1, 2016: Biochemical Journal
Michael Ionescu, Kenji Yokota, Elena Antonova, Angelica Garcia, Ellen Beaulieu, Terry Hayes, Anthony T Iavarone, Steven E Lindow
UNLABELLED: Cell density-dependent regulation of gene expression in Xylella fastidiosa that is crucial to its switching between plant hosts and insect vectors is dependent on RpfF and its production of 2-enoic acids known as diffusible signal factor (DSF). We show that X. fastidiosa produces a particularly large variety of similar, relatively long-chain-length 2-enoic acids that are active in modulating gene expression. Both X. fastidiosa itself and a Pantoea agglomerans surrogate host harboring X...
2016: MBio
Sandul Yasobant, Kranti Suresh Vora, Hemant Deepak Shewade, Kristi Sidney Annerstedt, Petros Isaakidis, Dileep V Mavalankar, Nishith B Dholakia, Ayesha De Costa
BACKGROUND: "Chiranjeevi Yojana (CY)", a state-led large-scale demand-side financing scheme (DSF) under public-private partnership to increase institutional delivery, has been implemented across Gujarat state, India since 2005. The scheme aims to provide free institutional childbirth services in accredited private health facilities to women from socially disadvantaged groups (eligible women). These services are paid for by the state to the private facility with the intention of service being free to the user...
2016: BMC Health Services Research
M H M Ahmed, A A Latiff, H Arof, S W Harun
We experimentally demonstrate a stable and simple mode locked erbium doped fiber laser (EDFL) utilizing passive few-layer molybdenum disulfide (MoS<sub>2</sub>) as a saturable absorber. The MoS<sub>2</sub> is obtained by liquid phase exfoliation before it is embedded in a polymer composite film and then inserted in the laser cavity. A stable soliton pulse train started at a low threshold pump power of 20 mW in the anomalous dispersion regime after fine-tuning the rotation of the polarization controller...
May 20, 2016: Applied Optics
Dan Chen, Kai Yang, Li Wei, Hongyu Wang
Bioelectrochemical denitrification system (BEDS) is a promising technology for nitrate removal from wastewaters. The hazards and effects concerning p-nitrophenol (PNP) towards BEDS lack enough investigations and possess great research prospects. This study investigated how PNP affected the nitrate removal efficiency, microbial communities, functional denitrifying genes abundances, nitrate and nitrite reductase activities, diffusible signal factors (DSF) release, and extracellular polymeric substances (EPS) production in the BEDS...
October 2016: Bioresource Technology
Yaping Yang, Kefan Zhang, Yawei Wang, Mengjia Li, Xiaoxue Sun, Zhihong Liang, Liwei Wang, Lixin Chen, Haifeng Yang, Linyan Zhu
Disulfiram (DSF) has been proved to have broad-spectrum anti-alcoholism effects, and it is also found to show stronger anti-tumor effects after chelating with Cu(2+) to form DSF-Cu complex. In this work, we studied the anti-tumor activity of DSF-Cu in MCF-7 cells by flow cytometry, confocal laser scanning microscope, and atomic force microscopy to clarify the underlying anti-tumor mechanisms. MCF-7 cells were incubated with 50, 100, 150, 200, and 250 nM DSF chelated with 10 µM CuCl2 for 24 h. The results showed that DSF-Cu could induce the accumulation of MCF-7 cells in G2/M phase and apoptosis in a concentration-dependent manner...
June 29, 2016: Scanning
Christoph Giese, Jonathan Eras, Anne Kern, Martin A Schärer, Guido Capitani, Rudi Glockshuber
The complex between the bacterial type 1 pilus subunit FimG and the peptide corresponding to the N-terminal extension (termed donor strand, Ds) of the partner subunit FimF (DsF) shows the strongest reported noncovalent molecular interaction, with a dissociation constant (KD ) of 1.5×10(-20)  m. However, the complex only exhibits a slow association rate of 330 m(-1)  s(-1) that limits technical applications, such as its use in affinity purification. Herein, a structure-based approach was used to design pairs of FimGt (a FimG variant lacking its own N-terminal extension) and DsF variants with enhanced electrostatic surface complementarity...
August 1, 2016: Angewandte Chemie
Umesh Yadava, Matthew W Vetting, Nawar Al Obaidi, Michael S Carter, John A Gerlt, Steven C Almo
The uptake of exogenous solutes by prokaryotes is mediated by transport systems embedded in the plasma membrane. In many cases, a solute-binding protein (SBP) is utilized to bind ligands with high affinity and deliver them to the membrane-bound components responsible for translocation into the cytoplasm. In the present study, Avi_5305, an Agrobacterium vitis SBP belonging to Pfam13407, was screened by differential scanning fluorimetry (DSF) and found to be stabilized by D-glucosamine and D-galactosamine. Avi_5305 is the first protein from Pfam13407 shown to be specific for amino sugars, and co-crystallization resulted in structures of Avi_5305 bound to D-glucosamine and D-galactosamine...
June 2016: Acta Crystallographica. Section F, Structural Biology Communications
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