Dimebon Does Not Ameliorate Pathological Changes Caused by Expression of Truncated (1–120) Human Alpha-Synuclein in Dopaminergic Neurons of Transgenic Mice

Background: Recent clinical studies have demonstrated that dimebon, a drug originally designed and used as a non-selective antihistamine, ameliorates symptoms and delays progress of mild to moderate forms of Alzheimer’s and Huntington’s diseases. Although the mechanism of dimebon action on pathological processes in degenerating brain is elusive, results of studies carried out in cell cultures and animal models suggested that this drug might affect the process of pathological accumulation and aggregation of various proteins involved in the pathogenesis of proteinopathies. However, the effect of this drug on the pathology caused by overexpression and aggregation of alpha-synuclein, including Parkinson’s disease (PD), has not been assessed. Objective: To test if dimebon affected alpha-synuclein-induced pathology using a transgenic animal model. Methods: We studied the effects of chronic dimebon treatment on transgenic mice expressing the C-terminally truncated (1–120) form of human alpha-synuclein in dopaminergic neurons, a mouse model that recapitulates several biochemical, histopathological and behavioral characteristics of the early stage of PD. Results: Dimebon did not improve balance and coordination of aging transgenic animals or increase the level of striatal dopamine, nor did it prevent accumulation of alpha-synuclein in cell bodies of dopaminergic neurons. Conclusion: Our observations suggest that in the studied model of alpha-synucleinopathy dimebon has very limited effect on certain pathological alterations typical of PD and related diseases

Toward the Integrated Marine Debris Observing System

Plastics and other artificial materials pose new risks to the health of the ocean. Anthropogenic debris travels across large distances and is ubiquitous in the water and on shorelines, yet, observations of its sources, composition, pathways, and distributions in the ocean are very sparse and inaccurate. Total amounts of plastics and other man-made debris in the ocean and on the shore, temporal trends in these amounts under exponentially increasing production, as well as degradation processes, vertical fluxes, and time scales are largely unknown. Present ocean circulation models are not able to accurately simulate drift of debris because of its complex hydrodynamics. In this paper we discuss the structure of the future integrated marine debris observing system (IMDOS)thatisrequiredtoprovidelong-termmonitoringofthestateofthisanthropogenic pollution and support operational activities to mitigate impacts on the ecosystem and on the safety of maritime activity. The proposed observing system integrates remote sensing and in situ observations. Also, models are used to optimize the design of the system and, in turn, they will be gradually improved using the products of the system. Remote sensing technologies will provide spatially coherent coverage and consistent surveying time series at local to global scale. Optical sensors, including high-resolution imaging, multi- and hyperspectral, fluorescence, and Raman technologies, as well as SAR will be used to measure different types of debris. They will be implemented in a variety of platforms, from hand-held tools to ship-, buoy-, aircraft-, and satellite-based sensors. A network of in situ observations, including reports from volunteers, citizen scientists and ships of opportunity, will be developed to provide data for calibration/validation of remote sensors and to monitor the spread of plastic pollution and other marine debris. IMDOS will interact with other observing systems monitoring physical, chemical, and biological processes in the ocean and on shorelines as well as the state of the ecosystem, maritime activities and safety, drift of sea ice, etc. The synthesized data will support innovative multi-disciplinary research and serve a diverse community of users

Current perspectives of the signaling pathways directing neural crest induction

The neural crest is a migratory population of embryonic cells with a tremendous potential to differentiate and contribute to nearly every organ system in the adult body. Over the past two decades, an incredible amount of research has given us a reasonable understanding of how these cells are generated. Neural crest induction involves the combinatorial input of multiple signaling pathways and transcription factors, and is thought to occur in two phases from gastrulation to neurulation. In the first phase, FGF and Wnt signaling induce NC progenitors at the border of the neural plate, activating the expression of members of the Msx, Pax, and Zic families, among others. In the second phase, BMP, Wnt, and Notch signaling maintain these progenitors and bring about the expression of definitive NC markers including Snail2, FoxD3, and Sox9/10. In recent years, additional signaling molecules and modulators of these pathways have been uncovered, creating an increasingly complex regulatory network. In this work, we provide a comprehensive review of the major signaling pathways that participate in neural crest induction, with a focus on recent developments and current perspectives. We provide a simplified model of early neural crest development and stress similarities and differences between four major model organisms: Xenopus, chick, zebrafish, and mouse