Molecular Switches at the Synapse Emerge from Receptor and Kinase Traffic

Changes in the synaptic connection strengths between neurons are believed to play a role in memory formation. An important mechanism for changing synaptic strength is through movement of neurotransmitter receptors and regulatory proteins to and from the synapse. Several activity-triggered biochemical events control these movements. Here we use computer models to explore how these putative memory-related changes can be stabilised long after the initial trigger, and beyond the lifetime of synaptic molecules. We base our models on published biochemical data and experiments on the activity-dependent movement of a glutamate receptor, AMPAR, and a calcium-dependent kinase, CaMKII. We find that both of these molecules participate in distinct bistable switches. These simulated switches are effective for long periods despite molecular turnover and biochemical fluctuations arising from the small numbers of molecules in the synapse. The AMPAR switch arises from a novel self-recruitment process where the presence of sufficient receptors biases the receptor movement cycle to insert still more receptors into the synapse. The CaMKII switch arises from autophosphorylation of the kinase. The switches may function in a tightly coupled manner, or relatively independently. The latter case leads to multiple stable states of the synapse. We propose that similar self-recruitment cycles may be important for maintaining levels of many molecules that undergo regulated movement, and that these may lead to combinatorial possible stable states of systems like the synapse

Influence of Physiochemical and Watershed Characteristics on Mercury Concentration in Walleye, Sander vitreus, M.

Elevated mercury concentration has been documented in a variety of fish and is a growing concern for human consumption. Here, we explore the influence of physiochemical and watershed attributes on mercury concentration in walleye (Sander vitreus, M.) from natural, glacial lakes in South Dakota. Regression analysis showed that water quality attributes were poor predictors of walleye mercury concentration (R2 = 0.57, p = 0.13). In contrast, models based on watershed features (e.g., lake level changes, watershed slope, agricultural land, wetlands) and local habitat features (i.e., substrate composition, maximum lake depth) explained 81% (p = 0.001) and 80% (p = 0.002) of the variation in walleye mercury concentration. Using an information theoretic approach we evaluated hypotheses related to water quality, physical habitat and watershed features. The best model explaining variation in walleye mercury concentration included local habitat features (Wi = 0.991). These results show that physical habitat and watershed features were better predictors of walleye mercury concentration than water chemistry in glacial lakes of the Northern Great Plains

Plant RuBisCo assembly in E. coli with five chloroplast chaperones including BSD2

Plant RuBisCo, a complex of eight large and eight small subunits, catalyzes the fixation of CO2 in photosynthesis. The low catalytic efficiency of RuBisCo provides strong motivation to reengineer the enzyme with the goal of increasing crop yields. However, genetic manipulation has been hampered by the failure to express plant RuBisCo in a bacterial host. We achieved the functional expression of Arabidopsis thaliana RuBisCo in Escherichia coli by coexpressing multiple chloroplast chaperones. These include the chaperonins Cpn60/Cpn20, RuBisCo accumulation factors 1 and 2, RbcX, and bundle-sheath defective-2 (BSD2). Our structural and functional analysis revealed the role of BSD2 in stabilizing an end-state assembly intermediate of eight RuBisCo large subunits until the small subunits become available. The ability to produce plant RuBisCo recombinantly will facilitate efforts to improve the enzyme through mutagenesis

Identification and molecular characterization of highly divergent RNA viruses in cattle, Uganda

The risk for the emergence of novel viral zoonotic diseases in animals and humans in Uganda is high given its geographical location with high biodiversity. We aimed to identify and characterize viruses in 175 blood samples from cattle selected in Uganda using molecular approaches. We identified 8 viral species belonging to 4 families (Flaviviridae, Peribunyaviridae, Reoviridae and Rhabdoviridae) and 6 genera (Hepacivirus, Pestivirus, Orthobunya-virus, Coltivirus, Dinovernavirus and Ephemerovirus). Four viruses were highly divergent and tetantively named Zikole virus (Family: Flaviviridae), Zeboroti virus (Family: Reoviridae), Zebtine virus (Family: Rhabdoviridae) and Kokolu virus (Family: Rhabdoviridae). In addition, Bovine Hepacivirus, Obodhiang virus, Aedes pseudoscutellaris reovirus and Schmallenberg virus were identified for the first time in Ugandan cattle. We report 8 viral species belonging to 4 viral families including divergent ones in the blood of cattle in Uganda. Hence, cattle may be reservoir hosts for likely emergence of novel viruses with pathogenic potential to cause zoonotic diseases in different species with serious public health implications

Pressures to Publish: Catalysts for the Loss of Scientific Writing Integrity?

Publishing research is the final step in the scientific process and is used as the primary means for disseminating research findings to the scientific community. Publishing can embody many personal motivations (e.g., gratification, seeing a finished product in print, desire to further science) for authors as well as professional benefits (e.g., promotion, tenure, future funding opportunities). As the scientific workforce and competition for jobs and funding increase, publishing productivity has become a driving factor for many authors, which may lead to writing practices that violate integrity. In this essay, we discuss writing actions that may be considered a violation of integrity in the context of traditional manuscript sections (introduction and discussion, methods, and results). We define “integrity” as consistency of actions that reflect honesty and truthfulness. Writing the introduction and discussion can be compared to an artistic creation because the rendition of the data may vary depending on the intentions and experience of the author. Some authors may be tempted to relate their research to a hot topic (e.g., climate change, model selection) in an attempt to increase publication success or maximize visibility in search engines, despite not having sufficient data to support their conclusions. Caution must be taken to not overextend the “story” beyond the bounds of the data. Modification of the methods and results sections contains the most extreme cases of scientific integrity violations (e.g., changing an alpha level, only presenting positive results, running numerous tests until desired outcome). Manipulation of methods or results is more difficult to detect by peer review. We believe that however destructive integrity violations may be, despite benefits to the author (e.g., accolades, publication, potential citations, promotion, etc.), the individual scientist should hold him- or herself accountable and to a high standard to avoid sacrificing integrity. Presión para publicar: catalizadores de la pérdida de integridad en la publicación científica Resume: La publicación es la etapa final del proceso científico y se utiliza como el medio principal para diseminar los hallazgos de una investigación. Para los autores, publicar puede implicar distintas motivaciones tanto personales (p.e. satisfacción, ver un producto final impreso, deseo de hacer más ciencia) como profesionales (p.e. promoción interna, basificación, oportunidades de financiamiento). A medida que se incrementa la fuerza laboral científica y la competencia por trabajo y financiamiento, la productividad en cuanto a las publicaciones se ha convertido en un factor determinante para muchos autores, lo cual puede dar pie a prácticas de publicación que comprometen la integridad. En este ensayo se discuten aquellas prácticas de publicación que se considera que comprometen la integridad en el contexto de las secciones habituales que conforman un artículo (introducción y discusión, métodos y resultados). Se define la integridad como la consistencia en acciones que reflejan honestidad y veracidad. Escribir la introducción y discusión se compara con una creación artística en cuanto a que la interpretación de los datos puede variar dependiendo de las intenciones y experiencia del autor. Algunos autores pueden estar tentados a relacionar su investigación a un tópico de actualidad (p.e. cambio climático, selección de modelos) en un intento por incrementar el éxito de la publicación y maximizar la posibilidad de ser encontrados mediante motores de búsqueda, a pesar de que no cuentan con suficientes datos como para apoyar sus conclusiones. Se debe tener cuidado para no extender la historia más allá de los límites que establecen los datos. La modificación de las secciones de métodos y resultados implica los casos más extremos de violaciones a la integridad (p.e. cambiar el nivel de alfa, presentar sólo resultados positivos, realizar numerosas pruebas hasta que salga el resultado esperado). La manipulación de los métodos o los resultados resulta particularmente difícil de detectar durante el proceso de revisión por pares. Creemos que no obstante lo destructivas que puedan ser las violaciones a la integridad y a pesar de los beneficios que obtengan los autores (p.e. premios, potencial de citación, promociones, etc.), el individuo científico debe mantener su sentido de responsabilidad y sus estándares en alto con el fin de evitar sacrificar su integridad