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Mechanism research

Salvatore Alaimo, Alfredo Pulvirenti
The wealth of knowledge and omic data available in drug research allowed the rising of several computational methods in drug discovery field yielding a novel and exciting application called drug repositioning. Several computational methods try to make a high-level integration of all the knowledge in order to discover unknown mechanisms. In this chapter we present an in-depth review of data resources and computational models for drug repositioning.
2019: Methods in Molecular Biology
Emiliano Macaluso
One of the ultimate goals of cognitive neuroscience is to understand how the brain works in the real world. Functional imaging with naturalistic stimuli provides us with the opportunity to study the brain in situations similar to the everyday life. This includes the processing of complex stimuli that can trigger many types of signals related both to the physical characteristics of the external input and to the internal knowledge that we have about natural objects and environments. In this chapter, I will first outline different types of stimuli that have been used in naturalistic imaging studies...
December 15, 2018: Current Topics in Behavioral Neurosciences
Michael Mason, Jeremy Mennis, Michael Russell, Mathew Moore, Aaron Brown
Adolescents with depression disorders have higher rates of substance use. In order to advance contextually relevant mental health interventions, basic research is needed to test social ecological mechanisms hypothesized to influence adolescent depression and substance use. Accordingly, we conducted growth curve modeling with a sample of 248 urban adolescents to determine if depression's effect on substance use was dependent upon peer network health (sum of peer risk and protective behaviors) and activity space risk (likelihood of high-risk behaviors at routine locations)...
December 14, 2018: Journal of Abnormal Child Psychology
Whitney D Fosco, Michael J Kofler, R Matt Alderson, Stephanie J Tarle, Joseph S Raiker, Dustin E Sarver
Inhibition is a key neurocognitive domain in ADHD that is commonly assessed with the stop-signal task. The stop-signal involves both "go" and "stop" trials; previous research indicates that response times are reliably slower to "go" trials during tasks with vs. without intermittent "stop" trials. However, it is unclear whether this pattern reflects deliberate slowing to maximize inhibitory success (performance adjustment hypothesis) and/or disrupted bottom-up information processing due to increased cognitive demands (dual-task hypothesis)...
December 13, 2018: Journal of Abnormal Child Psychology
David W Bearl, Debra A Dodd, Cary Thurm, Matt Hall, Jonathan H Soslow, Brian Feingold, Justin Godown
Right ventricular (RV) failure is a potentially fatal complication following heart transplantation (HTx). Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that is used to decrease pulmonary vascular resistance immediately post-HTx to reduce the risk of RV failure. The aim of this study was to describe utilization patterns, costs, and outcomes associated with post-transplant iNO use in children. All pediatric HTx recipients (2002-2016) were identified from a unique linked PHIS/SRTR dataset. Post-HTx iNO use was determined based on hospital billing data...
December 13, 2018: Pediatric Cardiology
Aleksandra Łachmańska, Paweł Tecmer, Örs Legeza, Katharina Boguslawski
Understanding the binding mechanism in neptunyl clusters formed due to cation-cation interactions is of crucial importance in nuclear waste reprocessing and related areas of research. Since experimental manipulations with such species are often rather limited, we have to rely on quantum-chemical predictions of their electronic structures and spectroscopic parameters. In this work, we present a state-of-the-art quantum chemical study of the T-shaped and diamond-shaped neptunyl(v) and neptunyl(vi) dimers. Specifically, we scrutinize their molecular structures, (implicit and explicit) solvation effects, the interplay of static and dynamical correlation, and the influence of spin-orbit coupling on the ground state and lowest-lying excited states for different total spin states and total charges of the neptunyl dications...
December 14, 2018: Physical Chemistry Chemical Physics: PCCP
Todd F Alamin, Vijay Agarwal, Alicia Zagel, Albi Qeli
Background: Pain while sitting is the primary complaint of many patients with lumbar spinal ailments, including those with discogenic low back pain and lumbar disc herniations. There has been little basic research on the different mechanical stresses that different sitting positions place on the spine. To demonstrate the effect of different sitting positions on lumbar intersegmental relationships. Methods: Twenty healthy male volunteer subjects were recruited. Lateral X-rays of the lower lumbar spine were taken in four positions: (I) relaxed lateral standing; (II) "standard" sitting position; (III) sitting on a "kneeling" chair; and (IV) unsupported sitting on a stool...
September 2018: Journal of Spine Surgery (Hong Kong)
Michèlle van der Does, Peter Knippertz, Philipp Zschenderlein, R Giles Harrison, Jan-Berend W Stuut
Giant mineral dust particles (>75 μm in diameter) found far from their source have long puzzled scientists. These wind-blown particles affect the atmosphere's radiation balance, clouds, and the ocean carbon cycle but are generally ignored in models. Here, we report new observations of individual giant Saharan dust particles of up to 450 μm in diameter sampled in air over the Atlantic Ocean at 2400 and 3500 km from the west African coast. Past research points to fast horizontal transport, turbulence, uplift in convective systems, and electrical levitation of particles as possible explanations for this fascinating phenomenon...
December 2018: Science Advances
Theresa E Gildner, Nawi Ng, Fan Wu, Yanfei Guo, J Josh Snodgrass, Paul Kowal
Evidence suggests that cognitive decline in older adults is influenced by cardiovascular health (CVH), with metabolic and vascular mechanisms hypothesized to underlie the etiology of cognitive impairment. Research in high-income nations suggests that improved CVH is linked with decreased cognitive impairment risk, but it is unclear if this pattern is evident in low-income countries. Nationally-representative data collected in China were drawn from the World Health Organization's Study on global AGing and adult health Wave 1 (2007-2010; n = 11,295)...
2018: Frontiers in Public Health
Maria Jose Martinez-Harms, Stefan Gelcich, Rainer M Krug, Fleur J F Maseyk, Hannah Moersberger, Archi Rastogi, Geoffrey Wambugu, Cornelia B Krug, Eva M Spehn, Unai Pascual
Sustainability is a key challenge for humanity in the context of complex and unprecedented global changes. Future Earth, an international research initiative aiming to advance global sustainability science, has recently launched knowledge-action networks (KANs) as mechanisms for delivering its research strategy. The research initiative is currently developing a KAN on "natural assets" to facilitate and enable action-oriented research and synthesis towards natural assets sustainability. 'Natural assets' has been adopted by Future Earth as an umbrella term aiming to translate and bridge across different knowledge systems and different perspectives on peoples' relationships with nature...
2018: Sustainability science
Måns Nilsson, Elinor Chisholm, David Griggs, Philippa Howden-Chapman, David McCollum, Peter Messerli, Barbara Neumann, Anne-Sophie Stevance, Martin Visbeck, Mark Stafford-Smith
Pursuing integrated research and decision-making to advance action on the sustainable development goals (SDGs) fundamentally depends on understanding interactions between the SDGs, both negative ones ("trade-offs") and positive ones ("co-benefits"). This quest, triggered by the 2030 Agenda, has however pointed to a gap in current research and policy analysis regarding how to think systematically about interactions across the SDGs. This paper synthesizes experiences and insights from the application of a new conceptual framework for mapping and assessing SDG interactions using a defined typology and characterization approach...
2018: Sustainability science
Takashi Saito, Takaomi C Saido
Alzheimer's disease (AD) is the most common type of neurocognitive disorder. Although both amyloid β peptide deposition and neurofibrillary tangle formation in the AD brain have been established as pathological hallmarks of the disease, many other factors contribute in a complex manner to the pathogenesis of AD before clinical symptoms of the disease become apparent. Longitudinal pathophysiological processes cause patients' brains to exist in a state of chronic neuroinflammation, with glial cells acting as key regulators of the neuroinflammatory state...
November 2018: Clinical & Experimental Neuroimmunology
Man Wang, Shuai Jiang, Wei Wu, Fei Yu, Wenguang Chang, Peifeng Li, Kun Wang
Non-coding RNAs (ncRNAs) are functional RNA molecules that are transcribed from DNA but not translated into proteins. ncRNAs function as key regulators of gene expression and chromatin modification. Recently, the functional role of ncRNAs in teleost fish has been extensively studied. Teleost fish are a highly diverse group among the vertebrate lineage. Fish are also important in terms of aquatic ecosystem, food production and human life, being the source of animal proteins worldwide and models of biomedical research...
2018: Frontiers in Immunology
Xuelian Wang, Xiumin Huang, Youzhong Zhang
Human papillomaviruses (HPV) are the first viruses to have been acknowledged to prompt carcinogenesis, and they are linked with cancers of the uterine cervix, anogenital tumors, and head and neck malignancies. This paper examines the structure and primary genomic attributes of HPV and highlights the clinical participation of the primary HPV serotypes, focusing on the roles that HPV-16 and 18 play in carcinogenesis. The mechanisms that take place in the progression of cervical neoplasia are described. The oncogenic proteins E6 and E7 disrupt control of the cell cycle by their communication with p53 and retinoblastoma protein...
2018: Frontiers in Microbiology
Franka Thurm, Nicolas Zink, Shu-Chen Li
Goal-directed behavior requires sufficient resource allocation of cognitive control processes, such as the ability to prioritize relevant over less relevant information in working memory. Findings from neural recordings in animals and human multimodal imaging studies suggest that reward incentive mechanisms could facilitate the encoding and updating of context representations, which can have beneficial effects on working memory performance in young adults. In order to investigate whether these performance enhancing effects of reward on working memory processes are still preserved in old age, the current study aimed to investigate whether aging alters the effects of reward anticipation on the encoding and updating mechanisms in working memory processing...
2018: Frontiers in Psychology
Brienna Perelli-Harris, Stefanie Hoherz, Fenaba Addo, Trude Lappegård, Ann Evans, Sharon Sassler, Marta Styrc
Extensive research has found that marriage provides health benefits to individuals, particularly in the U.S. The rise of cohabitation, however, raises questions about whether simply being in an intimate co-residential partnership conveys the same health benefits as marriage. Here, we use OLS regression to compare differences between partnered and unpartnered, and cohabiting and married individuals with respect to self-rated health in mid-life, an understudied part of the lifecourse. We pay particular attention to selection mechanisms arising in childhood and characteristics of the partnership...
2018: Population Research and Policy Review
Johan W S Vlaeyen, Chris G Maher, Katja Wiech, Jan Van Zundert, Carolina Beraldo Meloto, Luda Diatchenko, Michele C Battié, Marielle Goossens, Bart Koes, Steven J Linton
Low back pain affects individuals of all ages and is a leading contributor to disease burden worldwide. Despite advancements in assessment and treatment methods, the management of low back pain remains a challenge for researchers and clinicians alike. One reason for the limited success in identifying effective treatments is the large variation in the manifestations, possible causes, precipitating and maintaining factors, course, prognosis and consequences in terms of activity interference and quality of life...
December 13, 2018: Nature Reviews. Disease Primers
Bin Zhou, Rui Guo
The dysregulation of transcription factors has an important impact on the oncogenesis and tumor progression. Nonetheless, its functions in colorectal cancer metastasis are still unclear. In this study, four transcription factors (HNF4A, HSF1, MECP2 and RAD21) were demonstrated to be associated with the metastasis of colorectal cancer in both RNA and protein levels. To comprehensively explore the intrinsic mechanisms, we profiled the molecular landscape of these metastasis-related transcription factors from multiple perspectives...
December 13, 2018: Scientific Reports
Marc Humbert, Christophe Guignabert, Sébastien Bonnet, Peter Dorfmüller, James R Klinger, Mark R Nicolls, Andrea J Olschewski, Soni S Pullamsetti, Ralph T Schermuly, Kurt R Stenmark, Marlene Rabinovitch
Clinical and translational research has played a major role in advancing our understanding of pulmonary hypertension (PH), including pulmonary arterial hypertension and other forms of PH with severe vascular remodelling ( e.g. chronic thromboembolic PH and pulmonary veno-occlusive disease). However, PH remains an incurable condition with a high mortality rate, underscoring the need for a better transfer of novel scientific knowledge into healthcare interventions. Herein, we review recent findings in pathology (with the questioning of the strict morphological categorisation of various forms of PH into pre- or post-capillary involvement of pulmonary vessels) and cellular mechanisms contributing to the onset and progression of pulmonary vascular remodelling associated with various forms of PH...
December 13, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Ashley E Mason, Laura Saslow, Patricia J Moran, Sarah Kim, Hiba Abousleiman, Alison Hartman, Robert Richler, Samantha Schleicher, Wendy Hartogensis, Elissa S Epel, Frederick Hecht
BACKGROUND: Diet patterns have a profound influence on glycemic control for individuals with type 2 diabetes (T2DM), and craving-related eating is an important obstacle to dietary adherence. A growing body of research suggests that carbohydrate-restricted (CR) diets can improve glycemic control and reduce medication dependence in T2DM. However, limited data speak to the effects of long-term adherence to CR diets. Mindful eating training has been shown to reduce craving-related eating in overweight populations but has yet to be examined as a behavioral support for dietary adherence in T2DM...
September 19, 2018: JMIR Research Protocols
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