Nitric Oxide and Cyclic GMP Regulate Retinal Patterning in the Optic Lobe of Drosophila

AbstractThe photoreceptors of Drosophila express a nitric oxide–sensitive guanylate cyclase during the first half of metamorphosis, when postsynaptic elements in the optic lobe are being selected. Throughout this period, the optic lobes show NADPH-diaphorase activity and stain with an antibody to nitric oxide synthase (NOS). The NOS inhibitor L-NAME, the NO scavenger PTIO, the sGC inhibitor ODQ, and methylene blue, which inhibits NOS and guanylate cyclase, each caused the disorganization of retinal projections and extension of photoreceptor axons beyond their normal synaptic layers in vitro. The disruptive effects of L-NAME were prevented with the addition of 8-bromo-cGMP. These results suggest NO and cGMP act to stabilize retinal growth cones at the start of synaptic assembly

Pedagogical Matters: New Materialisms and Curriculum Studies

This edited collection takes up the wild and sudden surge of new materialisms in the field of curriculum studies. New materialisms shift away from the strong focus on discourse associated with the linguistic or cultural turn in theory and toward recent work in the physical and biological sciences; in doing so, they posit ontologies of becoming that re-configure our sense of what a human person is and how that person relates to the more-than-human ecologies in which it is nested. Ignited by an urgency to disrupt the dangers of anthropocentrism and systems of domination in the work of curriculum and pedagogy, this book builds upon the axiom that agency is not a uniquely human capacity but something inherent in all matter. This collection blurs the boundaries of human and non-human, animate and inanimate, to focus on webs of interrelations. Each chapter explores these questions while attending to the ethical, aesthetic, and political tasks of education—both in and out of school contexts. It is essential reading for anyone interested in feminist, queer, anti-racist, ecological, and posthumanist theories and practices of education.https://scholarship.richmond.edu/bookshelf/1236/thumbnail.jp

Anglocentrism in the Academy : On Linguistic Privilege, Mastery and Hoito

Peer reviewe

Queer Sonic Cultures: An Affective Walking-Composing Project

Walking in nature has long been associated with creativity. Yet walking’s associated research and artistic practices remain dogged by representationalism. Concomitantly, intersectional concerns of race, gender, and dis/ability determine what kinds of bodies are allowed to walk where (and in this case, the where is Brexit-era Britain). This article attempts to navigate the complexity of these tensions, contextualizing a five-day walking research-creation project along St. Cuthbert’s Way that we called Queer Sonic Cultures. As academics and artists interested in the relationship between walking and composition, our initial propositions are to become affected as we walked and to create sonic cultures (songs) using whatever affected us along the way. In using research-creation as a research methodology, we understand our artistic compositional practice of co-creating lyrics-melody-harmony-production-arrangement as the research. Unlike some forms of arts-based research that use an artistic form to disseminate research findings, in research-creation the artistic practice is the research and the theory. In the interests of continuing to make this apparent, we shall prefer to describe this contextualizing article as Academic Liner Notes. The Academic Liner Notes begin with a brief description of the location of the walk, contextualized within the tradition of walking and composing in the British landscape, and the use of sound-based methods and literature to represent such landscapes. Following this, we will introduce research-creation as a methodology contextualized within affect studies. We argue that the resultant sonic cultures (nine in total) rather than representing the walk, in fact, more-than-representationally intensify the affective dimensions of the relations we were part of along the way

A/autisms:: a “queer labor of the incommensurate”: holding onto the friction between different orientations towards autism in an early childhood research-creation project

In this paper, I propose “A/autisms” as an organizing concept for considering the complex intersection of Autistic identity, autistic disability, and the contingency of the diagnosis “autism” in educational research. I draw from Neuroqueer(ing) Noise—my doctoral research-creation project in an integrated, mainstream early childhood classroom—to consider how this intersection might help us orient towards A/autisms as artists, researchers, and teachers. Moreover, I suggest that A/autisms might be understood as a methodology for reorienting toward the human subject in the ontological turn. This paper is of relevance to researchers in the field of critical autism studies, as well as educational researchers interested in “post”-humanism, feminist materialisms, and arts-based research

CDK-dependent Hsp70 phosphorylation controls G1 cyclin abundance and cell-cycle progression

In budding yeast, the essential functions of Hsp70 chaperones Ssa1-4 are regulated through expression level, isoform specificity, and cochaperone activity. Suggesting a novel regulatory paradigm, we find that phosphorylation of Ssa1 T36 within a cyclin-dependent kinase (CDK) consensus site conserved among Hsp70 proteins alters cochaperone and client interactions. T36 phosphorylation triggers displacement of Ydj1, allowing Ssa1 to bind the G1 cyclin Cln3 and promote its degradation. The stress CDK Pho85 phosphorylates T36 upon nitrogen starvation or pheromone stimulation, destabilizing Cln3 to delay onset of S phase. In turn, the mitotic CDK Cdk1 phosphorylates T36 to block Cln3 accumulation in G2/M. Suggesting broad conservation from yeast to human, CDK-dependent phosphorylation of Hsc70 T38 similarly regulates Cyclin D1 binding and stability. These results establish an active role for Hsp70 chaperones as signal transducers mediating growth control of G1 cyclin abundance and activity

CDK-Dependent Hsp70 Phosphorylation Controls G1 Cyclin Abundance and Cell-Cycle Progression

In budding yeast, the essential functions of Hsp70 chaperones Ssa1–4 are regulated through expression level, isoform specificity, and cochaperone activity. Suggesting a novel regulatory paradigm, we find that phosphorylation of Ssa1 T36 within a cyclin-dependent kinase (CDK) consensus site conserved among Hsp70 proteins alters cochaperone and client interactions. T36 phosphorylation triggers displacement of Ydj1, allowing Ssa1 to bind the G1 cyclin Cln3 and promote its degradation. The stress CDK Pho85 phosphorylates T36 upon nitrogen starvation or pheromone stimulation, destabilizing Cln3 to delay onset of S phase. In turn, the mitotic CDK Cdk1 phosphorylates T36 to block Cln3 accumulation in G2/M. Suggesting broad conservation from yeast to human, CDK-dependent phosphorylation of Hsc70 T38 similarly regulates Cyclin D1 binding and stability. These results establish an active role for Hsp70 chaperones as signal transducers mediating growth control of G1 cyclin abundance and activity

Factors Influencing Sleep Difficulty and Sleep Quantity in the Citizen Pscientist Psoriatic Cohort.

IntroductionSleep is essential for overall health and well-being, yet more than one-third of adults report inadequate sleep. The prevalence is higher among people with psoriasis, with up to 85.4% of the psoriatic population reporting sleep disruption. Poor sleep among psoriasis patients is particularly concerning because psoriasis is independently associated with many of the same comorbidities as sleep dysfunction, including cardiovascular disease, obesity, and depression. Given the high prevalence and serious consequences of disordered sleep in psoriasis, it is vital to understand the nature of sleep disturbance in this population. This study was designed to help meet this need by using survey data from Citizen Pscientist, an online patient portal developed by the National Psoriasis Foundation.MethodsOur analysis included 3118 participants who identified as having a diagnosis by a physician of psoriasis alone or psoriasis with psoriatic arthritis. Demographic information, psoriasis severity and duration, sleep apnea status, smoking and alcohol consumption, itch timing, and sleep characteristics were included. Two separate multivariate logistic regression models in STATA were used to determine whether the presence of psoriatic arthritis, age, gender, body mass index, comorbid sleep apnea, psoriasis severity, timing of worst itch, smoking status, or high-risk alcohol consumption were associated with sleep difficulty or low sleep quantity, defined by the American Academy of Sleep Medicine as less than 7 h of sleep per night on average.ResultsResults from the multivariate logistic regressions found that sleep difficulty was associated with psoriatic arthritis (OR 2.15, 95% CI [1.79-2.58]), female gender (2.03 [1.67-2.46]), obese body mass index (BMI ≥ 30) (1.25 [1.00-1.56]), sleep apnea (1.41 [1.07-1.86]), psoriasis severity of moderate (1.59 [1.30-1.94]) or severe (2.40 [1.87-3.08]), and smoking (1.60 [1.26-2.02]). Low sleep quantity was associated with obese BMI (1.62 [1.29-2.03]), sleep apnea (1.30 [1.01-1.68]), psoriasis severity of moderate (1.41 [1.16-1.72]) or severe (1.40 [1.11-1.76]), and smoking (1.62 [1.31-2.00]). Sleep difficulty and low sleep quantity were not associated with age, alcohol consumption, or timing of worst itch.ConclusionThese results are potentially meaningful in several aspects. We identify an important distinction between sleep difficulty and sleep quantity in psoriatic disease, whereby having psoriatic arthritis and being female are each associated with sleep difficulty despite no association with low sleep quantity. Furthermore, there is conflicting evidence from prior studies as to whether psoriasis severity is associated with sleep difficulty, but this well-powered, large study revealed a strong, graded relationship between psoriasis severity and both sleep difficulty and low sleep quantity. Overall, our results show that both sleep difficulty and low sleep quantity were associated with multiple factors in this analysis of a large psoriatic cohort. These findings suggest that dermatologists may gather clinically useful information by screening psoriatic patients for trouble sleeping and low sleep quantity to identify potential comorbidities and to more effectively guide disease management

Heat Shock Protein 70 Prevents both Tau Aggregation and the Inhibitory Effects of Preexisting Tau Aggregates on Fast Axonal Transport

Aggregation and accumulation of the microtubule-associated protein tau are associated with cognitive decline and neuronal degeneration in Alzheimer's disease and other tauopathies. Thus, preventing the transition of tau from a soluble state to insoluble aggregates and/or reversing the toxicity of existing aggregates would represent a reasonable therapeutic strategy for treating these neurodegenerative diseases. Here we demonstrate that molecular chaperones of the heat shock protein 70 (Hsp70) family are potent inhibitors of tau aggregation in vitro, preventing the formation of both mature fibrils and oligomeric intermediates. Remarkably, addition of Hsp70 to a mixture of oligomeric and fibrillar tau aggregates prevents the toxic effect of these tau species on fast axonal transport, a critical process for neuronal function. When incubated with preformed tau aggregates, Hsp70 preferentially associated with oligomeric over fibrillar tau, suggesting that prefibrillar oligomeric tau aggregates play a prominent role in tau toxicity. Taken together, our data provide a novel molecular basis for the protective effect of Hsp70 in tauopathies