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Tânia G Lucas, Cláudio M Gomes, Bárbara J Henriques
Systematic identification of buffer formulations and small molecule chaperones that improve the expression, stability, and storage of proteins with therapeutic interest has gained enormous importance in biochemical research as well as in biotechnology and biomedical applications. In particular, the biochemical characterization of disease-related proteins and their genetic variants that result in misfolding requires systematic determination of protein stability, screening of optimal buffer conditions for biophysical and structural studies, and in some cases, the identification of small molecule chaperones with the potential to ameliorate folding defects...
2019: Methods in Molecular Biology
Alexey K Shaytan, Hua Xiao, Grigoriy A Armeev, Daria A Gaykalova, Galina A Komarova, Carl Wu, Vasily M Studitsky, David Landsman, Anna R Panchenko
Hydroxyl-radical footprinting (HRF) is a powerful method for probing structures of nucleic acid-protein complexes with single-nucleotide resolution in solution. To tap the full quantitative potential of HRF, we describe a protocol, hydroxyl-radical footprinting interpretation for DNA (HYDROID), to quantify HRF data and integrate them with atomistic structural models. The stages of the HYDROID protocol are extraction of the lane profiles from gel images, quantification of the DNA cleavage frequency at each nucleotide and theoretical estimation of the DNA cleavage frequency from atomistic structural models, followed by comparison of experimental and theoretical results...
October 19, 2018: Nature Protocols
Stefan Reis, Tomáš Liška, Massimo Vieno, Edward J Carnell, Rachel Beck, Tom Clemens, Ulrike Dragosits, Samuel J Tomlinson, David Leaver, Mathew R Heal
Traditional approaches of quantifying population-level exposure to air pollution assume that concentrations of air pollutants at the residential address of the study population are representative for overall exposure. This introduces potential bias in the quantification of human health effects. Our study combines new UK Census data comprising information on workday population densities, with high spatio-temporal resolution air pollution concentration fields from the WRF-EMEP4UK atmospheric chemistry transport model, to derive more realistic estimates of population exposure to NO2 , PM2...
October 15, 2018: Environment International
Garry Papayan, Andrey Akopov
BACKGROUND: Visualization of Indocyanine Green (ICG) near-infrared (NIR) fluorescence is a promising technique for biomedical applications because of its deep tissue penetration, low autofluorescence, weak dependence on ambient light, safety for patients and medical staff. METHODS: To apply this technique to animal studies and clinical practice, we developed multispectral NIR fluorescence imaging system FLUM-808, which can be used in experimental studies and clinical practice, in open and endoscopic surgery (fluorescence-guided surgery)...
October 16, 2018: Photodiagnosis and Photodynamic Therapy
Mary E Rosenberger, Janet E Fulton, Matthew P Buman, Richard P Troiano, Michael A Grandner, David M Buchner, William L Haskell
The physiologic mechanisms by which the four activities of sleep, sedentary behavior, light-intensity physical activity (LIPA), and moderate-to-vigorous physical activity (MVPA) affect health are related, but these relationships have not been well explored in adults. Research studies have commonly evaluated how time spent in one activity affects health. Because one can only increase time in one activity by decreasing time in another, such studies cannot determine the extent that a health benefit is due to one activity versus due to reallocating time among the other activities...
October 18, 2018: Medicine and Science in Sports and Exercise
Guihong Cha, Zimin Chen, Ran Mo, Guangwen Lu, Beile Gao
Campylobacter jejuni is the leading cause of foodborne gastrointestinal illness worldwide, and chemotaxis plays an important role in its host colonization and pathogenesis. Although many studies on chemotaxis have focused on the physical organization and signaling mechanism of the system's protein complex, much less is known about the transcriptional regulation of its components. Here, we describe two novel regulators, CJJ81176_0275 and CJJ81176_0276 (designated as CheP and CheQ), which specifically activate the transcription of the chemotaxis core genes cheV, cheA and cheW in C...
October 19, 2018: Molecular Microbiology
Ignacio Rodriguez-Una, Augusto Azuara-Blanco
This review describes some of the most relevant recent advances in the development and application of new technologies for detecting and managing glaucoma, including imaging, visual function testing, and tonometry. The widespread availability of mobile technology in the developing world is improving health care delivery, for example, with smartphones and mobile applications that allow patient data to be assessed remotely by health care providers.
October 19, 2018: Asia-Pacific Journal of Ophthalmology
Hirofumi Iitsuka, Keiichi Koizumi, Akiko Inujima, Mikiko Suzaki, Yusuke Mizuno, Yoshiki Takeshita, Takeshi Eto, Yoshiki Otsuka, Ryo Shimada, Mengxin Liu, Keisuke Ikeda, Minoru Nakano, Ryo Suzuki, Kazuo Maruyama, Yue Zhou, Hiroaki Sakurai, Naotoshi Shibahara
Herbal medicine is mainly prepared from boiling herbal water extracts. Many epoch-making immunosuppressant drugs, such as glycyrrhizic acid (old example) and FTY720 (current example), were developed from herbal secondary metabolites in the boiling water extract by partition with organic solvents. However, few immunostimulants have been discovered by this method. Instead of the usual method, we aimed to find a novel immunostimulant component by two unique methods in the research of herbal medicine: ultracentrifugation and electron microscopy...
December 2018: Biochemistry and Biophysics Reports
Richard Gannotta, Shaista Malik, Alvin Y Chan, Kamran Urgun, Frank Hsu, Sumeet Vadera
The landscape of medicine in the United States has been slowly progressing toward a more holistic and individualized approach to healing. Part of this progress has been the integration between western and alternative forms of medicine, a concept that has been described as "integrative medicine." This approach to healthcare incorporates a patient's mind, spirituality, and sense of community into the healing process. Integrative medicine has been typically well received and the demand has been steadily increasing in primary US hospitals...
August 4, 2018: Curēus
Liang Liang, Yanyuan Ma, Ying Wei, Raymond J Carroll
Analysing secondary outcomes is a common practice for case-control studies. Traditional secondary analysis employs either completely parametric models or conditional mean regression models to link the secondary outcome to covariates. In many situations, quantile regression models complement mean-based analyses and provide alternative new insights on the associations of interest. For example, biomedical outcomes are often highly asymmetric, and median regression is more useful in describing the 'central' behaviour than mean regressions...
September 2018: Journal of the Royal Statistical Society. Series B, Statistical Methodology
Stephen A Sonstein, Rebecca J Namenek Brower, William Gluck, H Robert Kolb, Carmen Aldinger, Barbara E Bierer, Carolynn Thomas Jones
Competency standards for clinical research professionals are being developed across the enterprise, based largely on the Core Competency Framework put forth by the Joint Task Force for Clinical Trial Competency (JTF). In late 2016, representatives from organizations around the world convened at a workshop hosted by the Multi-Regional Clinical Trial Center of Brigham and Women's Hospital and Harvard (MRCT Center) to discuss their use of the standards. A number of modifications were suggested that resulted in the publication of JTF Framework 2...
October 18, 2018: Therapeutic Innovation & Regulatory Science
Laurent Tatu, Julien Bogousslavsky
The issue of First World War shell shock has been documented mainly from a medical perspective. Many medical texts dealing with war psychoneuroses and their aggressive treatments, such as electrotherapy, were published during the war. Accounts from shell-shocked soldiers are rare. Nevertheless, shell shock was described from a non-medical point of view by a few writers who had undergone or witnessed this pathology. Their texts deal mainly with the psychiatric forms, the most striking ones, but also with the more common concepts of commotion, emotion and pathological fear...
2018: Frontiers of Neurology and Neuroscience
Ross Cressman, Vlastimil Křivan
Classic bimatrix games, that are based on pair-wise interactions between two opponents in two different roles, do not consider the effect that interaction duration has on payoffs. However, interactions between different strategies often take different amounts of time. In this article, we further develop a new approach to an old idea that opportunity costs lost while engaged in an interaction affect individual fitness. We consider two scenarios: (i) individuals pair instantaneously so that there are no searchers, and (ii) searching for a partner takes positive time and populations consist of a mixture of singles and pairs...
October 15, 2018: Journal of Theoretical Biology
Zachary Boswell, Michael P Latham
Nuclear Magnetic Resonance (NMR) spectroscopy is particularly adept at site-specifically monitoring dynamic processes in proteins, such as protein folding, domain movements, ligand binding, and side chain rotations. By coupling the favorable spectroscopic properties of highly dynamic side chain methyl groups with Transverse Relaxation Optimized SpectroscopY (TROSY), it is now possible to routinely study such dynamic processes in large molecular weight proteins and complexes approaching 1 MDa. In this perspective, we describe many elegant methyl-based NMR experiments that probe slow (second) to fast (picosecond) dynamics in large systems...
October 18, 2018: Biochemistry
Joe Iwanaga, Emily Simonds, Marc Vetter, Mayank Patel, Rod J Oskouian, R Shane Tubbs
The inferior gluteal nerve has been traditionally described as a solely motor branch innervating the gluteus maximus. However, during routine dissection of the gluteal region, a cutaneous branch of the inferior gluteal nerve was identified. As the gluteal region is vulnerable to the development of pressure ulcers and iatrogenic injury with for example, surgical approaches and injection therapies, a comprehensive understanding of its cutaneous innervation is important. Therefore, the aim of this study was to elucidate the anatomy of this cutaneous branch of the inferior gluteal nerve in a series of cadavers...
October 18, 2018: Clinical Anatomy
Yuan Chen, Rui Zhu, Fang Ma, Jialin Mao, Eugene C Chen, Edna Choo, Srikumar Sahasranaman, Lichuan Liu
GDC-0810 was under development as an oral anti-cancer drug for the treatment of estrogen receptor-positive breast cancer as a single agent or in combination. In vitro data indicated that GDC-0810 is a potent inhibitor of OATP1B1/1B3. To assess clinical risk, PBPK model was developed to predict the transporter drug-drug interaction (tDDI) between GDC-0810 and pravastatin in human. The PBPK model was constructed in Simcyp® by integrating in vitro and in vivo data for GDC-0810. The prediction of human pharmacokinetics (PK) was verified using GDC-0810 phase I clinical PK data...
October 18, 2018: Biopharmaceutics & Drug Disposition
Quan Zhang, Ning Zhang, Lei Kang, Gang Hu, Xiangguo Yan, Xiaorong Ding, Qizhi Fu, Yuanting Zhang, Ni Zhao, Junfeng Gao, Strangman Gary E
For many cerebrovascular diseases (CVDs) both blood pressure (BP) and hemodynamic changes are important clinical variables. In this paper, we describe the development of a novel approach to noninvasively and simultaneously monitor cerebral hemodynamics, blood pressure and other important parameters at high temporal resolution (250Hz sampling rate). In this approach, cerebral hemodynamics are acquired using NIRS based sensors and algorithms, whereas continuous blood pressure is acquired by superficial temporal artery (STA) tonometry with pulse transit time based drift correction...
October 15, 2018: IEEE Journal of Biomedical and Health Informatics
Pedro Godinho, Lúcia Gonçalves, Paulo Muendane, Maria Dos Anjos Dixe, Elisabete Valente
Aim The American Society of Anesthesiologists scale is used worldwide for the assessment of the physical status of patients proposed for anaesthesia interventions. This study aims to assess the level of agreement of the last updated American Society of Anesthesiologists classification version, with the introduction of examples for each class, and search for variables that could promote inconsistency. Methods An online questionnaire was sent to anaesthesiology specialists and residents in Portugal, describing 10 fictitious clinical cases...
October 18, 2018: Journal of Perioperative Practice
Daniel Reker, J B Brown
High-throughput and high-content screening campaigns have resulted in the creation of large chemogenomic matrices. These matrices form the training data which is used to build ligand-target interaction models for pharmacological and chemical biology research. While academic, government, and industrial efforts continuously add to the ligand-target data pairs available for modeling, major research efforts are devoted to improving machine learning techniques to cope with the sparseness, heterogeneity, and size of available datasets as well as inherent noise and bias...
2018: Methods in Molecular Biology
Erika Girardi, Paula López, Sébastien Pfeffer
Every living organism has to constantly face threats from the environment and deal with a large number of pathogens against which it has to defend itself to survive. Among those, viruses represent a large class of obligatory intracellular parasites, which rely on their host machinery to multiply and propagate. As a result, viruses and their hosts have engaged in an ever-evolving arms race to be able to maintain their existence. The role played by micro (mi)RNAs in this ongoing battle has been extensively studied in the past 15 years and will be the subject of this review article...
2018: Frontiers in Genetics
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