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

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

Indigenous Methodology in Practice: Starting a Community-Based Research Center on the Yakama Reservation

In our paper, we examine the process, possibilities, and tensions of building a new community-based research center at a small liberal arts college on the Yakama Reservation. We view our work with the Center for Native Health & Culture as an example of human rights-based educational transformation, as our work is about honoring indigenous land, community, and values. This mission stands at odds with Western educational approaches, which typically view indigenous peoples, cultures, and well-being as a side note to frequently marginalized campus diversity initiatives. Our work to establish the new research center takes up the challenge of placing indigenous peoples’ health and culture at the center of the academic enterprise. We, as academics engaging in this work on traditional Yakama homeland, are uniquely situated to analyze and articulate this form of academic decolonization work. We draw from the interwoven liberation model proposed by Falcón and Jacob to critically examine our center’s work process and product to articulate our indigenous methodology in practice. Our indigenous methodology is guided by three principles: (a) understanding the importance of partnerships; (b) viewing our work in terms of building on existing strengths within campus and local tribal communities; (c) engaging in work that promotes a vision of academic excellence that has a “good spirit” and inspires all parties involved. We conclude by discussing some of the challenges faced in doing decolonizing work, and affirm the urgent need to further indigenize the academy

Decadal demographic shifts and size-dependent disturbance responses of corals in a subtropical warming hotspot

Funding supporting this research was provided by an Australian Research Council Discovery Early Career Research Award (DE230100141) and a University of Sydney Fellowship to BS, by the Australian Research Council Centre of Excellence for Coral Reef Studies (CE140100020) to JMP and others, the Australian Research Council Centre of Excellence for Environmental Decisions (CE110001014) and the Winifred Violet Scott Charitable Trust to MB, the Royal Geographical Society’s Ralph Brown Expedition Grant to MB and JC, the Natural Environment Research Council’s Sphere Doctoral Training Partnership to JC and the Natural Environment Research Council’s ONE Planet Doctoral Training Partnership (NE/S007512/1) and the European Commission’s Erasmus Traineeship to LL. This project has further received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant agreement TRIM-DLV-747102 to MB.Long-term demographic studies at biogeographic transition zones can elucidate how body size mediates disturbance responses. Focusing on subtropical reefs in eastern Australia, we examine trends in the size-structure of corals with contrasting life-histories and zoogeographies surrounding the 2016 coral bleaching event (2010–2019) to determine their resilience and recovery capacity. We document demographic shifts, with disproportionate declines in the number of small corals and long-term persistence of larger corals. The incidence of bleaching (Pocillopora, Turbinaria) and partial mortality (Acropora, Pocillopora) increased with coral size, and bleached corals had greater risk of partial mortality. While endemic Pocillopora experienced marked declines, decadal stability of Turbinaria despite bleaching, coupled with abundance increase and bleaching resistance in Acropora indicate remarkable resilience of these taxa in the subtropics. Declines in the number of small corals and variable associations with environmental drivers indicate bottlenecks to recovery mediated by inhibitory effects of thermal extremes for Pocillopora (heat stress) and Acropora (heat and cold stress), and stimulatory effects of chlorophyll-a for Turbinaria. Although our study reveals signs of resilience, it foreshadows the vulnerability of subtropical corals to changing disturbance regimes that include marine heatwaves. Disparity in population dynamics suggest that subtropical reefs are ecologically distinct from tropical coral reefs.Peer reviewe

Efficacy in Emergency Legal Preparedness Underlying the 2014 Ebola Outbreak

From its relative obscurity over the past three decades, Ebola viral disease (“EVD”) emerged as a substantial global biothreat in 2014 and 2015. The current outbreak of varied strains of Ebola, beginning in March 2014 in Guinea, is projected to impact hundreds of thousands of people over months, years, or even indefinitely. As of October 31, 2014, the spread of EVD was concentrated in several Af- rican countries (e.g., Sierra Leone, Liberia, Guinea, and an unrelated outbreak in Democratic Republic of Congo), with limited additional cases in Nigeria, Senegal, and Mali. Over 2,700 people are known to have died from Ebola in fewer than eight months in Liberia alone; the actual death toll may be far higher. At one point, the U.S. Centers for Disease Control and Prevention (“CDC”) estimated a worst-case scenario of 1.4 million new cases arising largely in already affected countries by early 2015. Reported cases in the affected regions are considerably less than these estimates, but with a fatality rate hovering near 50%, thousands more West Africans may perish before the end of this current outbreak

Efficacy in Emergency Legal Preparedness Underlying the 2014 Ebola Outbreak

From its relative obscurity over the past three decades, Ebola viral disease (“EVD”) emerged as a substantial global biothreat in 2014 and 2015. The current outbreak of varied strains of Ebola, beginning in March 2014 in Guinea, is projected to impact hundreds of thousands of people over months, years, or even indefinitely. As of October 31, 2014, the spread of EVD was concentrated in several Af- rican countries (e.g., Sierra Leone, Liberia, Guinea, and an unrelated outbreak in Democratic Republic of Congo), with limited additional cases in Nigeria, Senegal, and Mali. Over 2,700 people are known to have died from Ebola in fewer than eight months in Liberia alone; the actual death toll may be far higher. At one point, the U.S. Centers for Disease Control and Prevention (“CDC”) estimated a worst-case scenario of 1.4 million new cases arising largely in already affected countries by early 2015. Reported cases in the affected regions are considerably less than these estimates, but with a fatality rate hovering near 50%, thousands more West Africans may perish before the end of this current outbreak

Shock Wave Response of Iron-based In Situ Metallic Glass Matrix Composites

The response of amorphous steels to shock wave compression has been explored for the first time. Further, the effect of partial devitrification on the shock response of bulk metallic glasses is examined by conducting experiments on two iron-based in situ metallic glass matrix composites, containing varying amounts of crystalline precipitates, both with initial composition Fe_(49.7)Cr_(17.7)Mn_(1.9)Mo_(7.4)W_(1.6)B_(15.2)C_(3.8)Si_(2.4). The samples, designated SAM2X5-600 and SAM2X5-630, are X-ray amorphous and partially crystalline, respectively, due to differences in sintering parameters during sample preparation. Shock response is determined by making velocity measurements using interferometry techniques at the rear free surface of the samples, which have been subjected to impact from a high-velocity projectile launched from a powder gun. Experiments have yielded results indicating a Hugoniot Elastic Limit (HEL) to be 8.58 ± 0.53 GPa for SAM2X5-600 and 11.76 ± 1.26 GPa for SAM2X5-630. The latter HEL result is higher than elastic limits for any BMG reported in the literature thus far. SAM2X5-600 catastrophically loses post-yield strength whereas SAM2X5-630, while showing some strain-softening, retains strength beyond the HEL. The presence of crystallinity within the amorphous matrix is thus seen to significantly aid in strengthening the material as well as preserving material strength beyond yielding