Neuroscience, molecular biology, and the childhood roots of health disparities: Building a new framework for health promotion and disease prevention

Shonkoff, J. P., Boyce, W. T., & McEwen, B. S. (2009) JAMA, 301(21), 2252-2259 A scientific consensus is emerging that the origins of adult disease are often found among developmental and biological disruptions occurring during the early years of life. These early experiences can affect adult health in 2 ways—either by cumulative damage over time or by the biological embedding of adversities during sensitive developmental periods. In both cases, there can be a lag of many years, even decades, before early adverse experiences are expressed in the form of disease….

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Ecology of Borrelia burgdorferi sensu lato in Europe: transmission dynamics in multi-host systems, influence of molecular processes and effects of climate change

Author: Mannelli, A.; Bertolotti, L.; Gern, L.; Gray, J. Description: The analysis of different multi-host systems suggests that even hosts that are not capable of transmitting Borrelia burgdorferi sensu lato (s.l.) to the tick vector, Ixodes ricinus, or that are secondary reservoirs for these agents contribute to the intensity of transmission and to the overall risk of Lyme borreliosis, through the process of vector augmentation and pathogen amplification. On the other hand, above certain threshold densities, or in the presence of competition with primary reservoir hosts or low attachment rate…

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CP2K: An electronic structure and molecular dynamics software package – Quickstep: Efficient and accurate electronic structure calculations

Author: Kuhne, Thomas D.; Iannuzzi, Marcella; Del Ben, Mauro; Rybkin, Vladimir V.; Seewald, Patrick; Stein, Frederick; Laino, Teodoro; Khaliullin, Rustam Z.; Schutt, Ole; Schiffmann, Florian; Golze, Dorothea; Wilhelm, Jan; Chulkov, Sergey; Bani-Hashemian, Mohammad Hossein; Weber, Valery; Borstnik, Urban; Taillefumier, Mathieu; Jakobovits, Alice Shoshana; Lazzaro, Alfio; Pabst, Hans; Muller, Tiziano; Schade, Robert; Guidon, Manuel; Andermatt, Samuel; Holmberg, Nico; Schenter, Gregory K.; Hehn, Anna; Bussy, Augustin; Belleflamme, Fabian; Tabacchi, Gloria; Glob, Andreas; Lass, Michael; Bethune, Iain; Mundy, Christopher J.; Plessl, Christian; Watkins, Matt; VandeVondele, Joost; Krack, Matthias; Hutter, Jurg Description: CP2K is…

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Molecular signature of pancreatic adenocarcinoma: an insight from genotype to phenotype and challenges for targeted therapy

Author: Sahin, I.H.; Iacobuzio-Donahue, C.A.; O’Reilly, E.M. Description: INTRODUCTION: Pancreatic adenocarcinoma remains one of the most clinically challenging cancers despite an in-depth characterization of the molecular underpinnings and biology of this disease. Recent whole-genome-wide studies have elucidated the diverse and complex genetic alterations which generate a unique oncogenic signature for an individual pancreatic cancer patient and which may explain diverse disease behavior in a clinical setting. AREAS COVERED: In this review article, we discuss the key oncogenic pathways of pancreatic cancer including RAS-MAPK, PI3KCA and TGF-beta signaling, as well as…

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Drugs that target dynamic microtubules: a new molecular perspective

Author: Stanton, R.A.; Gernert, K.M.; Nettles, J.H.; Aneja, R. Description: Microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. As such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. Although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), the exact mechanism by…

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Trypanosoma cruzi-induced molecular mimicry and Chagas’ disease

Author: Girones, N.; Cuervo, H.; Fresno, M. Description: Chagas’ disease, caused by Trypanosoma cruzi, has been considered a paradigm of infection-induced autoimmune disease. Thus, the scarcity of parasites in the chronic phase of the disease contrasts with the severe cardiac pathology observed in approximately 30% of chronic patients and suggested a role for autoimmunity as the origin of the pathology. Antigen-specific and antigen-non-specific mechanisms have been described by which T. cruzi infection might activate T and B cells, leading to autoimmunity. Among the first mechanisms, molecular mimicry has been claimed…

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Scalable molecular dynamics with NAMD

Author: Phillips, J.C.; Braun, R.; Wang, W.; Gumbart, J.; Tajkhorshid, E.; Villa, E.; Chipot, C.; Skeel, R.D.; Kale, L.; Schulten, K. Description: NAMD is a parallel molecular dynamics code designed for high-performance simulation of large biomolecular systems. NAMD scales to hundreds of processors on high-end parallel platforms, as well as tens of processors on low-cost commodity clusters, and also runs on individual desktop and laptop computers. NAMD works with AMBER and CHARMM potential functions, parameters, and file formats. This article, directed to novices as well as experts, first introduces concepts…

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Inducible systemic RNA silencing in Caenorhabditis elegans

Author: Timmons, Lisa; Tabara, Hiroaki; Mello, Craig C.; Fire, Andrew Z. Description: Introduction of double-stranded RNA (dsRNA) can elicit a gene-specific RNA interference response in a variety of organisms and cell types. In many cases, this response has a systemic character in that silencing of gene expression is observed in cells distal from the site of dsRNA delivery. The molecular mechanisms underlying the mobile nature of RNA silencing are unknown. For example, although cellular entry of dsRNA is possible, cellular exit of dsRNA from normal animal cells has not been…

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The chemistry of small-molecule fluorogenic probes

Author: Grimm, J.B.; Heckman, L.M.; Lavis, L.D. Description: Chemical fluorophores find wide use in biology to detect and visualize different phenomena. A key advantage of small-molecule dyes is the ability to construct compounds where fluorescence is activated by chemical or biochemical processes. Fluorogenic molecules, in which fluorescence is activated by enzymatic activity, light, or environmental changes, enable advanced bioassays and sophisticated imaging experiments. Here, we detail the collection of fluorophores and highlight both general strategies and unique approaches that are employed to control fluorescence using chemistry. Subject headings: Boron Compounds/chemistry;…

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Rational design of fluorophores for in vivo applications

Author: Ptaszek, M. Description: Several classes of small organic molecules exhibit properties that make them suitable for fluorescence in vivo imaging. The most promising candidates are cyanines, squaraines, boron dipyrromethenes, porphyrin derivatives, hydroporphyrins, and phthalocyanines. The recent designing and synthetic efforts have been dedicated to improving their optical properties (shift the absorption and emission maxima toward longer wavelengths and increase the brightness) as well as increasing their stability and water solubility. The most notable advances include development of encapsulated cyanine dyes with increased stability and water solubility, squaraine rotaxanes with…

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