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Vibeke Strand, Eun Bong Lee, Roy Fleischmann, Rieke E Alten, Tamas Koncz, Samuel H Zwillich, David Gruben, Bethanie Wilkinson, Sriram Krishnaswami, Gene Wallenstein
OBJECTIVES: To compare patient-reported outcomes (PROs) in methotrexate (MTX)-naive patients (defined as no prior treatment or ≤3 doses) receiving tofacitinib versus MTX. METHODS: In the 24-month, phase III, randomised, controlled, ORAL Start trial (NCT01039688), patients were randomised 2:2:1 to receive tofacitinib 5 mg two times per day (n=373), tofacitinib 10 mg two times per day (n=397) or MTX (n=186). PROs assessed included Patient Global Assessment of disease (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and health-related quality of life (Short Form-36 [SF-36])...
2016: RMD Open
Tan Ying Peh, Grace Meijuan Yang, Lalit Kumar Radha Krishna, Alethea Chung Peng Yee
BACKGROUND: Doctors report inadequate training and lack confidence in providing palliative care. Although palliative care training improves self-assessed competence, it is not known whether the duration of a palliative medicine (PM) posting affects the extent of improvement in confidence. OBJECTIVE: The aim of this study was to determine whether the duration of a PM posting affects the extent of improvement in doctors' confidence in various aspects of palliative care...
October 17, 2016: Journal of Palliative Medicine
Anna Juhasova, Martina Baliova, Frantisek Jursky
Coomassie Brilliant Blue interacts with proteins and even though the interactions exhibit variation due to the amino acid content, reported dye interactions with individual proteins appear to be relatively stable. Here we report an atypical dynamic interaction of glycine transporters 1 and 2 N-termini with Coomassie dye, resulting in intramolecular interference with their Bradford assay. These proteins exhibit classic protein-Coomassie G-250 complex with absorption maximum at 595 nm, which within minutes starts to decrease and parallel increase of absorbance shoulders above 300 and 700 nm is observed...
October 15, 2016: Protein Journal
Hugo A Araújo, Ernesto P Raposo
We revisit the problem of calculating the survival probability of Lévy flights in a finite interval with absorbing boundaries. Our approach is based on the master equation for discrete Lévy fliers, previously considered to treat the semi-infinite domain. We argue that, although the semi-infinite case can be treated exactly due to Wiener-Hopf factorization, the approximation involved in the problem with the finite interval is actually fairly good. We evidence the shift in the universal behavior of the long-term survival probability from the exponential decay in the presence of two absorbing barriers to the Sparre-Andersen power-law dependence in the single-barrier limit...
September 2016: Physical Review. E
Kinga Morsanyi, Eileen O'Mahony, Teresa McCormack
Recent evidence has highlighted the important role that number ordering skills play in arithmetic abilities (e.g., Lyons & Beilock, 2011). In fact, Lyons et al. (2014) demonstrated that although at the start of formal mathematics education number comparison skills are the best predictors of arithmetic performance, from around the age of 10, number ordering skills become the strongest numerical predictors of arithmetic abilities. In the current study, we demonstrated that number comparison and ordering skills were both significantly related to arithmetic performance in adults, and the effect size was greater in the case of ordering skills...
October 13, 2016: Quarterly Journal of Experimental Psychology: QJEP
George Milis, Panayiotis Kolios, Gaby Van Melick, Toni Staykova, Ira Helsloot, Georgios Ellinas, Christos Panayiotou, Marios Polycarpou
The medical emergency response comprises a domain with complex processes, encompassing multiple heterogeneous entities, from organisations involved in the response to human actors to key information sources. Due to the heterogeneity of the entities and the complexity of the domain, it is important to fully understand the individual processes in which the components are involved and their inter-operations, before attempting to design any technological tool for coordination and decision support. This work starts with the gluing together and visualisation of the interactions of involved entities into a conceptual model, along the identified five workspaces of emergency response...
September 2016: Healthcare Technology Letters
Qiang Shao
Large-scale conformational changes in proteins are important for their functions. Tracking the conformational change in real time at the level of a single protein molecule, however, remains a great challenge. In this article, we present a novel in silico approach with the combination of normal mode analysis and integrated-tempering-sampling molecular simulation (NMA-ITS) to give quantitative data for exploring the conformational transition pathway in multi-dimensional energy landscapes starting only from the knowledge of the two endpoint structures of the protein...
October 12, 2016: Physical Chemistry Chemical Physics: PCCP
Maria D Molina-Sánchez, Fernando M García-Rodríguez, Nicolás Toro
The functional unit of mobile group II introns is a ribonucleoprotein particle (RNP) consisting of the intron-encoded protein (IEP) and the excised intron RNA. The IEP has reverse transcriptase activity but also promotes RNA splicing, and the RNA-protein complex triggers site-specific DNA insertion by reverse splicing, in a process called retrohoming. In vitro reconstituted ribonucleoprotein complexes from the Lactococcus lactis group II intron Ll.LtrB, which produce a double strand break, have recently been studied as a means of developing group II intron-based gene targeting methods for higher organisms...
2016: Frontiers in Molecular Biosciences
Yuki Kawashima Sonoyama, Toshihiro Tajima, Masanobu Fujimoto, Akiko Hasegawa, Naoki Miyahara, Rei Nishimura, Yuichiro Hashida, Atsushi Hayashi, Keiichi Hanaki, Susumu Kanzaki
Pseudohypoaldosteronism type 1 (PHA1) is a rare genetic disease characterized by resistance to aldosterone, and the renal form of PHA1 is associated with heterozygous inactivating mutations in NR3C2, which encodes mineralocorticoid receptor (MR). Here we report a case of renal PHA1 due to a novel frameshift mutation in NR3C2. A 10-day-old Japanese male infant, born at 39 weeks gestation (birth weight, 2,946 g), was admitted to our hospital because of lethargy and vomiting, with a 6.7% weight loss since birth...
October 5, 2016: Endocrine Journal
Francisco J Valero-Cuevas, Verena Klamroth-Marganska, Carolee J Winstein, Robert Riener
BACKGROUND: Comparing the efficacy of alternative therapeutic strategies for the rehabilitation of motor function in chronically impaired individuals is often inconclusive. For example, a recent randomized clinical trial (RCT) compared robot-assisted vs. conventional therapy in 77 patients who had had chronic motor impairment after a cerebrovascular accident. While patients assigned to robotic therapy had greater improvements in the primary outcome measure (change in score on the upper extremity section of the Fugl-Meyer assessment), the absolute difference between therapies was small, which left the clinical relevance in question...
October 11, 2016: Journal of Neuroengineering and Rehabilitation
Sindhu Ghanta, Michael I Jordan, Kivanc Kose, Dana H Brooks, Milind Rajadhyaksha, Jennifer G Dy
Segmenting objects of interest from 3D datasets is a common problem encountered in biological data. Small field of view and intrinsic biological variability combined with optically subtle changes of intensity, resolution and low contrast in images make the task of segmentation difficult, especially for microscopy of unstained living or freshly excised thick tissues. Incorporating shape information in addition to the appearance of the object of interest can often help improve segmentation performance. However, shapes of objects in tissue can be highly variable and design of a flexible shape model that encompasses these variations is challenging...
October 5, 2016: IEEE Transactions on Image Processing: a Publication of the IEEE Signal Processing Society
Petr Jeřábek, Jan Florián, Václav Martínek
Cytochrome P450 1A2 (P450 1A2, CYP1A2) is a membrane-bound enzyme that oxidizes a broad range of hydrophobic substrates. The structure and dynamics of both the catalytic and trans-membrane (TM) domains of this enzyme in the membrane/water environment were investigated using a multiscale computational approach, including coarse-grained and all-atom molecular dynamics. Starting from the spontaneous self-assembly of the system containing the TM or soluble domain immersed in randomized dilauroyl phosphatidylcholine (DLPC)/water mixture into their respective membrane-bound forms, we reconstituted the membrane-bound structure of the full-length P450 1A2...
September 26, 2016: Physical Chemistry Chemical Physics: PCCP
José Vargas-Asencio, Klaudia Wojciechowska, Maia Baskerville, Annika L Gomez, Keith L Perry, Jeremy R Thompson
In analyzing grapevine clones infected with grapevine red blotch associated virus, we identified a small number of isometric particles of approximately 30nm in diameter from an enriched fraction of leaf extract. A dominant protein of 25kDa was isolated from this fraction using SDS-PAGE and was identified by mass spectrometry as belonging to grapevine asteroid mosaic associated virus (GAMaV). Using a combination of three methods RNA-Seq, sRNA-Seq, and Sanger sequencing of RT- and RACE-PCR products, we obtained a full-length genome sequence consisting of 6719 nucleotides without the poly(A) tail...
October 5, 2016: Virus Research
C S Hakkers, J E Arends, R E Barth, S Du Plessis, A I M Hoepelman, M Vink
HIV-associated neurocognitive disorder (HAND) is a frequently occurring comorbidity of HIV infection. Evidence suggests this condition starts subclinical before a progression to a symptomatic stage. Blood oxygenated level dependent (BOLD) fMRI has shown to be a sensitive tool to detect abnormal brain function in an early stage and might therefore be useful to evaluate the effect of HIV infection on brain function. An extensive literature search was performed in June 2015. Eligibility criteria for included studies were as follows: (1) conducting with HIV-positive patients, (2) using BOLD fMRI, and (3) including a HIV-negative control group...
October 7, 2016: Journal of Neurovirology
Matthias G Beuerle, Neil P Dufton, Anna M Randi, Ian R Gould
The ETS family of transcription factors regulate gene targets by binding to a core GGAA DNA-sequence. The ETS factor ERG is required for homeostasis and lineage-specific functions in endothelial cells, some subset of haemopoietic cells and chondrocytes; its ectopic expression is linked to oncogenesis in multiple tissues. To date details of the DNA-binding process of ERG including DNA-sequence recognition outside the core GGAA-sequence are largely unknown. We combined available structural and experimental data to perform molecular dynamics simulations to study the DNA-binding process of ERG...
October 3, 2016: Molecular BioSystems
Supriyo Bhattacharya, Romelia Salomon-Ferrer, Sangbae Lee, Nagarajan Vaidehi
GPCRs are transmembrane receptors involved in diverse biological functions. Despite the diversity in their amino acid sequences, class A GPCRs exhibit a conserved structural topology and possibly common mechanism of receptor activation. To understand how this high sequence diversity translates to a conserved functional mechanism, we have compared the dynamic behavior of eight class A GPCRs comprising of six biogenic amine receptors, and the adenosine A2A and a peptide receptor protease activated receptor 1...
October 6, 2016: Journal of Chemical Theory and Computation
Rucha Harishbhai Mehta, Manivel Ponnuchamy, Jitendra Kumar, Nagaraja Reddy Rama Reddy
De novo assembly of reads produced by next-generation sequencing (NGS) technologies offers a rapid approach to obtain expressed gene sequences for non-model organisms. Senna (Cassia angustifolia Vahl.) is a drought-tolerant annual undershrub of Caesalpiniaceae, a subfamily of Fabaceae. There are insufficient transcriptomic and genomic data in public databases for understanding the molecular mechanism underlying the drought tolerance of senna. Therefore, the main purpose of this study was to know the transcriptome profile of senna, with special reference to drought stress...
October 5, 2016: Functional & Integrative Genomics
Takehiko Ueyama, Yuzuru Ninoyu, Shin-Ya Nishio, Takushi Miyoshi, Hiroko Torii, Koji Nishimura, Kazuma Sugahara, Hideaki Sakata, Dean Thumkeo, Hirofumi Sakaguchi, Naoki Watanabe, Shin-Ichi Usami, Naoaki Saito, Shin-Ichiro Kitajiri
DIAPH1 encodes human DIA1, a formin protein that elongates unbranched actin. The c.3634+1G>T DIAPH1 mutation causes autosomal dominant nonsyndromic sensorineural hearing loss, DFNA1, characterized by progressive deafness starting in childhood. The mutation occurs near the C-terminus of the diaphanous autoregulatory domain (DAD) of DIA1, which interacts with its N-terminal diaphanous inhibitory domain (DID), and may engender constitutive activation of DIA1. However, the underlying pathogenesis that causes DFNA1 is unclear...
October 5, 2016: EMBO Molecular Medicine
J Stephen Dumler, Sara H Sinclair, Valeria Pappas-Brown, Amol C Shetty
Anaplasma phagocytophilum, an obligate intracellular prokaryote, infects neutrophils, and alters cardinal functions via reprogrammed transcription. Large contiguous regions of neutrophil chromosomes are differentially expressed during infection. Secreted A. phagocytophilum effector AnkA transits into the neutrophil or granulocyte nucleus to complex with DNA in heterochromatin across all chromosomes. AnkA binds to gene promoters to dampen cis-transcription and also has features of matrix attachment region (MAR)-binding proteins that regulate three-dimensional chromatin architecture and coordinate transcriptional programs encoded in topologically-associated chromatin domains...
2016: Frontiers in Cellular and Infection Microbiology
Han Wen, Feng Qin, Wenjun Zheng
As a key cellular sensor, the TRPV1 cation channel undergoes a gating transition from a closed state to an open state in response to various physical and chemical stimuli including noxious heat. Despite years of study, the heat activation mechanism of TRPV1 gating remains enigmatic at the molecular level. Toward elucidating the structural and energetic basis of TRPV1 gating, we have performed molecular dynamics (MD) simulations (with cumulative simulation time of 3 μs), starting from the high-resolution closed and open structures of TRPV1 solved by cryo-electron microscopy...
October 3, 2016: Proteins
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