CASK regulates CaMKII autophosphorylation in neuronal growth, calcium signaling, and learning

Calcium (Ca2+)/calmodulin (CaM)-dependent kinase II (CaMKII) activity plays a fundamental role in learning and memory. A key feature of CaMKII in memory formation is its ability to be regulated by autophosphorylation, which switches its activity on and off during synaptic plasticity. The synaptic scaffolding protein CASK (calcium (Ca2+)/calmodulin (CaM) associated serine kinase) is also important for learning and memory, as mutations in CASK result in intellectual disability and neurological defects in humans. We show that in Drosophila larvae, CASK interacts with CaMKII to control neuronal growth and calcium signalling. Furthermore, deletion of the CaMK-like and L27 domains of CASK (CASK β null) or expression of overactive CaMKII (T287D) produced similar effects on synaptic growth and Ca2+ signalling. CASK overexpression rescues the effects of CaMKII overactivity, consistent with the notion that CASK and CaMKII act in a common pathway that controls these neuronal processes. The reduction in Ca2+ signalling observed in the CASK β null mutant caused a decrease in vesicle trafficking at synapses. In addition, the decrease in Ca2+ signalling in CASK mutants was associated with an increase in Ether-à-go-go (EAG) potassium (K+) channel localisation to synapses. Reducing EAG restored the decrease in Ca2+ signalling observed in CASK mutants to the level of wildtype, suggesting that CASK regulates Ca2+ signalling via EAG. CASK knockdown reduced both appetitive associative learning and odour evoked Ca2+ responses in Drosophila mushroom bodies, which are the learning centres of Drosophila. Expression of human CASK in Drosophila rescued the effect of CASK deletion on the activity state of CaMKII, suggesting that human CASK may also regulate CaMKII autophosphorylation

Human dimensions of global environmental change: A review of frameworks and research gaps.

This review of current knowledge in, and development of, priorities for research into the human dimensions of global environmental change has been conducted to assist the Foundation for Research Science and Technology to formulate their research needs agenda. An overview of the emergence of the human dimension of the global environmental change research field is used as a prelude to a review of the international literature on frameworks for conducting human dimensions research. The terminology used in the human dimension field is diverse. An attempt is therefore made to consolidate the myriad of definitions for key concepts, in order to form a basis for human dimensions research in New Zealand and build a platform for the remainder of this report. Three disciplinary areas of academic inquiry were explored in the context of human dimensions of global environmental change research: economics, law and biological sciences. These disciplinary perspectives are reviewed through the international literature and in a New Zealand context. A conceptual framework for research into the human dimensions of global environmental change is provided based on the knowledge-base developed from the both international and New Zealand research. Core concepts, such as found in multidisciplinary and transdisciplinary research are reviewed in historical context to form the basis for a specific research framework for New Zealand. Some general needs for research are derived from the New Zealand framework. The remainder of this report details the methods used for drawing out expert opinion on the priorities for research on the human dimensions of global environmental change in the context of information, knowledge and method. Thirty-eight interviews and two hui were conducted and 254 research needs defined by questions were obtained. A modified Delphi technique was applied to the questions and prioritised lists of responses are provided. The final list Provides European/Pakeha and Māori perspectives. Divergence and convergence between the European/Pakeha and Māori responses is provided, as well as justification for the prioritisation stance that is taken. This research had four outputs: A conceptual framework for considering the human dimensions of global environmental changes and research contributions; A description of the gaps in knowledge that impede effective response to global change and provisional research needs: one for New Zealand generally, and one on Māori in particular; A network of end-users and research providers that are cognisant of, and contributors to, the human dimensions research assessment; A set of priority research needs pertaining to the human dimensions of global environmental change, in a form suitable for use by FRST

Factors Influencing the Adoption of Russian Varroa-Resistant Honey Bees

Factors influencing the adoption of Russian Varroa-Resistant honey bees were assessed. Logit results indicate factors associated with the adoption include sales, internet use, and contact with other beekeepers. Negatively associated factors are age and income. Future adoption depends upon previous use and perception.Agribusiness,

Trust as a predictor of innovation network ties in project teams

We examine the influence of trust on the formation of social network ties for the idea generation and idea realisation stages of innovation. Drawing on data from 153 employees working in project teams at two firms, we find two dimensions of trustworthiness, Ability and Benevolence, predict tie formation for both idea generation and idea realisation, whereas Integrity predicts tie formation for idea generation only. Moderation analyses across both firms and stages of innovation reveal that a lack of benevolence makes ability largely irrelevant as a criterion for choosing a partner for innovation activities, whereas high benevolence increases the extent to which ability influences partner choice. Additionally, a lack of integrity makes ability either irrelevant or a negative criterion for partner section. Overall the results suggest that people need to perceive others as benevolent and not lacking in integrity in order to seek out their skills and knowledge for innovation in project teams

The Growing Concern of Poverty in the United States: an exploration of food prices and poverty on obesity rates for low-income citizens

Studies demonstrate the link between income and obesity, determining factors to explain the strong correlation between high body mass index and low socioeconomic status. Many focus on uncovering predictors but few use a systems approach: identifying the interaction among predictors and their relative magnitude concerning obesity. This study asks: do poverty or food price indicators have a statistically stronger relationship with obesity? By collecting data, evaluating trends, and analyzing statistics, this study extends research by revealing a stronger relationship between obesity and food prices as opposed to obesity and poverty

KCNQ Channels Show Conserved Ethanol Block and Function in Ethanol Behaviour

In humans, KCNQ2/3 channels form an M-current that regulates neuronal excitability, with mutations in these channels causing benign neonatal familial convulsions. The M-current is important in mechanisms of neural plasticity underlying associative memory and in the response to ethanol, with KCNQ controlling the release of dopamine after ethanol exposure. We show that dKCNQ is broadly expressed in the nervous system, with targeted reduction in neuronal KCNQ increasing neural excitability and KCNQ overexpression decreasing excitability and calcium signalling, consistent with KCNQ regulating the resting membrane potential and neural release as in mammalian neurons. We show that the single KCNQ channel in Drosophila (dKCNQ) has similar electrophysiological properties to neuronal KCNQ2/3, including conserved acute sensitivity to ethanol block, with the fly channel (IC(50) = 19.8 mM) being more sensitive than its mammalian ortholog (IC(50) = 42.1 mM). This suggests that the role of KCNQ in alcohol behaviour can be determined for the first time by using Drosophila. We present evidence that loss of KCNQ function in Drosophila increased sensitivity and tolerance to the sedative effects of ethanol. Acute activation of dopaminergic neurons by heat-activated TRP channel or KCNQ-RNAi expression produced ethanol hypersensitivity, suggesting that both act via a common mechanism involving membrane depolarisation and increased dopamine signalling leading to ethanol sedation

Evolutionary dynamics of tumor progression with random fitness values

Most human tumors result from the accumulation of multiple genetic and epigenetic alterations in a single cell. Mutations that confer a fitness advantage to the cell are known as driver mutations and are causally related to tumorigenesis. Other mutations, however, do not change the phenotype of the cell or even decrease cellular fitness. While much experimental effort is being devoted to the identification of the different functional effects of individual mutations, mathematical modeling of tumor progression generally considers constant fitness increments as mutations are accumulated. In this paper we study a mathematical model of tumor progression with random fitness increments. We analyze a multi-type branching process in which cells accumulate mutations whose fitness effects are chosen from a distribution. We determine the effect of the fitness distribution on the growth kinetics of the tumor. This work contributes to a quantitative understanding of the accumulation of mutations leading to cancer phenotypes.Comment: 33 pages, 2 Figure