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Anirban Basu, Gopinatha Suresh Kumar
Interaction of proflavine with hemoglobin (Hgb) was studied employing spectroscopy, calorimetry, and atomic force microscopy. The equilibrium constant was found to be of the order 10(4)M(-1). The quenching of Hgb fluorescence by proflavine was due to the complex formation. Calculation of the molecular distance (r) between the donor (β-Trp37 of Hgb) and acceptor (proflavine) suggested that energy can be efficiently transferred from the β-Trp37 residue at the α1β2 interface of the protein to the dye. Proflavine induced significant secondary structural changes in Hgb...
October 12, 2016: Journal of Photochemistry and Photobiology. B, Biology
Wenyan Xu, Daniel Kool, Derek K O'Flaherty, Ashley Keating, Lauralicia Sacre, Martin Egli, Anne Marietta Noronha, Christopher James Wilds, Linlin Zhao
DNA interstrand cross-links (ICLs) are cytotoxic DNA lesions derived from reactions of DNA with a number of anti-cancer reagents as well as endogenous bifunctional electrophiles. Deciphering the DNA repair mechanisms of ICLs is important for understanding the toxicity of DNA cross-linking agents and for the development of effective chemotherapies. Previous research has focused on ICLs cross-linked with the N7 and N2 atoms of guanine as well as those formed at the N6 atom of adenine; however, little is known about the mutagenicity of O6-dG-derived ICLs...
October 21, 2016: Chemical Research in Toxicology
Marion Tegethoff, Esther Stalujanis, Angelo Belardi, Gunther Meinlschmidt
BACKGROUND: The objective was to estimate temporal associations between mental disorders and physical diseases in adolescents with mental-physical comorbidities. METHODS: This article bases upon weighted data (N = 6483) from the National Comorbidity Survey Adolescent Supplement (participant age: 13-18 years), a nationally representative United States cohort. Onset of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition lifetime mental disorders was assessed with the fully structured World Health Organization Composite International Diagnostic Interview, complemented by parent report...
2016: PloS One
Klaus Kratochwill, Michael Boehm, Rebecca Herzog, Katharina Gruber, Anton Michael Lichtenauer, Lilian Kuster, Dagmar Csaicsich, Andreas Gleiss, Seth L Alper, Christoph Aufricht, Andreas Vychytil
BACKGROUND: Peritonitis and ultrafiltration failure remain serious complications of chronic peritoneal dialysis (PD). Dysfunctional cellular stress responses aggravate peritoneal injury associated with PD fluid exposure, potentially due to peritoneal glutamine depletion. In this randomized cross-over phase I/II trial we investigated cytoprotective effects of alanyl-glutamine (AlaGln) addition to glucose-based PDF. METHODS: In a prospective randomized cross-over design, 20 stable PD outpatients underwent paired peritoneal equilibration tests 4 weeks apart, using conventional acidic, single chamber 3...
2016: PloS One
Pirow Bekker, Daniel Dairaghi, Lisa Seitz, Manmohan Leleti, Yu Wang, Linda Ertl, Trageen Baumgart, Sarah Shugarts, Lisa Lohr, Ton Dang, Shichang Miao, Yibin Zeng, Pingchen Fan, Penglie Zhang, Daniel Johnson, Jay Powers, Juan Jaen, Israel Charo, Thomas J Schall
The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood...
2016: PloS One
Gregory Plotnikoff, Melissa Barber
INTRODUCTION: Single-disorder or single-organ-system clinical practice guidelines are often of limited usefulness in guiding effective management of patients with chronic multidimensional signs and symptoms. The presence of multiple long-standing medical problems in a given patient despite intensive medical effort suggests that addressing systemic core imbalances could complement more narrowly focused approaches. CASE PRESENTATION: A 72-year-old man experiencing longstanding depression, fatigue, irritable bowel syndrome, and chronic pain in the context of additional refractory illnesses was assessed and treated, guided by a system-oriented approach to underlying core imbalances termed functional medicine...
October 14, 2016: Permanente Journal
Philippe Hermand, Annick Vandercammen, Emmanuel Mertens, Emmanuel Di Paolo, Vincent Verlant, Philippe Denoël, Fabrice Godfroid
The use of protein antigens able to protect against the majority of Streptococcus pneumoniae serotypes is envisaged as stand-alone and/or complement to the current capsular polysaccharide-based pneumococcal vaccines. Pneumolysin (Ply) is a key virulence factor that is highly conserved in amino acid sequence across pneumococcal serotypes, and therefore may be considered as a vaccine target. However, native Ply cannot be used in vaccines due to its intrinsic cytolytic activity. In the present work a completely, irreversibly detoxified pneumolysin (dPly) has been generated using an optimized formaldehyde treatment...
October 21, 2016: Human Vaccines & Immunotherapeutics
Liang Guo, Liqiang Zheng, Xiaofan Guo, Ye Chang, Xinghu Zhou, Yingxian Sun
BACKGROUND: Complement component 5 (C5) has been described to play an important role in the development and progression of atherosclerosis and cardiovascular disease. Our aim was to determine whether genetic variation of C5 was associated with ischemic stroke (IS) in northeast Chinese population. METHODS: We used a case-control study involving 386 IS patients and 386 non-IS controls from a rural population and determined the genotypes of five polymorphisms (rs12237774, rs17611, rs4837805, rs7026551, and rs1017119) of C5 gene by Snapshot single-nucleotide polymorphism genotyping assays to assess any links with IS...
October 21, 2016: Genetic Testing and Molecular Biomarkers
Syed T Ahmed, Fabio Parmeggiani, Nicholas J Weise, Sabine L Flitsch, Nicholas J Turner
Current routes to nitrogen-containing heteroarylalanines involve complex multistep synthesis and are often reliant on protection/deprotection steps and wasteful chromatographic purifications. In order to complement existing methodologies, a convenient telescopic strategy was developed for the synthesis of l-pyridylalanine analogues (12 examples) and other l-heteroarylalanines (5 examples) starting from the corresponding aldehydes. A phenylalanine ammonia lyase (PAL) from Anabaena variabilis was used as the biocatalyst to give conversions ranging between 88 and 95%, isolated yields of 32-60%, and perfect enantiopurity (>99% ee) by employing an additional deracemization cascade where necessary...
October 21, 2016: Organic Letters
Yun Ma, Russell F Algera, David B Collum
The reactivities and chemoselectivities of sodium diisopropylamide (NaDA) in N,N-dimethylethylamine (DMEA) are compared with those of lithium diisopropylamide (LDA) in tetrahydrofuran (THF). Metalations of arenes, epoxides, ketones, hydrazones, dienes, and alkyl and vinyl halides are represented. The positive attributes of NaDA-DMEA include high solubility, stability, resistance to solvent decomposition, and ease of preparation. The high reactivities and chemoselectivities often complement those of LDA-THF.
October 21, 2016: Journal of Organic Chemistry
Valentina Talarico, Monica Aloe, Alice Monzani, Roberto Miniero, Gianni Bona
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy defined by thrombocytopenia, non-immune microangiopathic hemolytic anemia and acute renal failure. HUS is typically classified into two primary types: 1) HUS due to infections, often associated with diarrhea (D+HUS, Shiga toxin-producing Escherichia Coli-HUS), with the rare exception of HUS due to a severe disseminated infection caused by Streptococcus; 2) HUS related to complement, such HUS is also known as "atypical HUS" and is not diarrhea associated (D-HUS, aHUS); but recent studies have shown other forms of HUS, that can occur in the course of systemic diseases or physiopathological conditions such as pregnancy, after transplantation or after drug assumption...
December 2016: Minerva Pediatrica
Kristine Carandang, Elizabeth A Pyatak, Cheryl L P Vigen
OBJECTIVE: In this study, we systematically reviewed the effectiveness of educational interventions falling within the scope of occupational therapy practice for people with rheumatoid arthritis (RA). These interventions included disease education, joint protection and energy conservation, psychosocial techniques, pain management, and a combination category. METHOD: Two databases, MEDLINE and CINAHL, and select journals were searched for randomized controlled trials published between January 2002 and June 2015...
November 2016: American Journal of Occupational Therapy: Official Publication of the American Occupational Therapy Association
Petr Stadlbauer, Liuba Mazzanti, Tristan Cragnolini, David J Wales, Philippe Derreumaux, Samuela Pasquali, Jiri Sponer
G-quadruplexes are the most important non-canonical DNA architectures. Many quadruplex-forming sequences, including the human telomeric sequence d(GGGTTA)n, have been investigated due to their implications in cancer and other diseases, and because of their potential in DNA-based nanotechnology. Despite availability of atomistic structural studies of folded G-quadruplexes, their folding pathways remain mysterious, and mutually contradicting models of folding coexist in the literature. Recent experiments convincingly demonstrated that G-quadruplex folding often takes days to reach the thermodynamics equilibrium...
October 21, 2016: Journal of Chemical Theory and Computation
Katie M Parkins, Amanda M Hamilton, Ashley V Makela, Yuanxin Chen, Paula J Foster, John A Ronald
Cellular MRI involves sensitive visualization of iron-labeled cells in vivo but cannot differentiate between dead and viable cells. Bioluminescence imaging (BLI) measures cellular viability, and thus we explored combining these tools to provide a more holistic view of metastatic cancer cell fate in mice. Human breast carcinoma cells stably expressing Firefly luciferase were loaded with iron particles, injected into the left ventricle, and BLI and MRI were performed on days 0, 8, 21 and 28. The number of brain MR signal voids (i...
October 21, 2016: Scientific Reports
Bruce Wen, Kirby R Campbell, Karissa Tilbury, Oleg Nadiarnykh, Molly A Brewer, Manish Patankar, Vikas Singh, Kevin W Eliceiri, Paul J Campagnola
Remodeling of the collagen architecture in the extracellular matrix (ECM) has been implicated in ovarian cancer. To quantify these alterations we implemented a form of 3D texture analysis to delineate the fibrillar morphology observed in 3D Second Harmonic Generation (SHG) microscopy image data of normal (1) and high risk (2) ovarian stroma, benign ovarian tumors (3), low grade (4) and high grade (5) serous tumors, and endometrioid tumors (6). We developed a tailored set of 3D filters which extract textural features in the 3D image sets to build (or learn) statistical models of each tissue class...
October 21, 2016: Scientific Reports
Alexander Bernt, Ashraf Y Rangrez, Matthias Eden, Andreas Jungmann, Sylvia Katz, Claudia Rohr, Oliver J Müller, Hugo A Katus, Samuel T Sossalla, Tatjana Williams, Oliver Ritter, Derk Frank, Norbert Frey
The objective of this study was to identify unknown modulators of Calcineurin (Cn)-NFAT signaling. Measurement of NFAT reporter driven luciferase activity was therefore utilized to screen a human cardiac cDNA-library (~10(7) primary clones) in C2C12 cells through serial dilutions until single clones could be identified. This extensive screening strategy culminated in the identification of SUMO2 as a most efficient Cn-NFAT activator. SUMO2-mediated activation of Cn-NFAT signaling in cardiomyocytes translated into a hypertrophic phenotype...
October 21, 2016: Scientific Reports
Kavita J Rawat, Nilakshi H Sabnis, Udit Saraf, Gaurav Surana
Vitamin D functions as a vitamin as well as a hormone. Its major skeletal actions are complemented by varied extra-skeletal functions. During the past decade, association between Vitamin D and its role in various non-skeletal morbidities have been recognized. It plays a role in decreasing the risk of many chronic illnesses like allergies, asthma, autoimmune diseases, diabetes, cancers, infections and cardiovascular disease. We report the case of a middle aged female with chronic quadriparesis and new onset anemia associated with Vitamin D deficiency...
October 2016: Journal of the Association of Physicians of India
Janine Naß, Mita Banerjee, Thomas Efferth, Anita Wohlmann
Illness is a disruptive experience that requires high-quality care. The best evidence-based medical treatment risks losing some of its efficacy, however, when patients feel misunderstood when faced with the complexity of their experiences. They might stop treatment, refuse to disclose relevant information or seek unsound alternatives. A narrative-based approach to health care understands the patient's case history as a narrative that can be read or analyzed like a story. In other words, this approach honors individual illness experiences through the stories that patients tell...
October 20, 2016: International Journal of Clinical Pharmacy
Brandon L Thompson, Christopher Birch, Daniel A Nelson, Jingyi Li, Jacquelyn A DuVall, Delphine Le Roux, An-Chi Tsuei, Daniel L Mills, Brian E Root, James P Landers
Current conventional methods utilized for forensic DNA analysis are time consuming and labor-intensive requiring large and expensive equipment and instrumentation. While more portable Rapid DNA systems have been developed, introducing them to a working laboratory still necessitates a high cost of initiation followed by the recurrent cost of the devices. This has highlighted the need for an inexpensive, rapid and portable DNA analysis tool for human identification in a forensic setting. In order for an integrated DNA analysis system such as this to be realized, device operations must always be concluded by a rapid separation of short-tandem repeat (STR) DNA fragments...
October 21, 2016: Lab on a Chip
Almudena Gómez-Hernández, Nuria Beneit, Sabela Díaz-Castroverde, Óscar Escribano
This review focuses on the contribution of white, brown, and perivascular adipose tissues to the pathophysiology of obesity and its associated metabolic and vascular complications. Weight gain in obesity generates excess of fat, usually visceral fat, and activates the inflammatory response in the adipocytes and then in other tissues such as liver. Therefore, low systemic inflammation responsible for insulin resistance contributes to atherosclerotic process. Furthermore, an inverse relationship between body mass index and brown adipose tissue activity has been described...
2016: International Journal of Endocrinology
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