Cyclase associated protein (CAP) and the physiological disassembly of actin

Actin dynamics are important for both driving cellular movement and maintaining cellular structure in apparently static tissues. Actin assembly and disassembly is an energy driven cycle that is utilized by cells to generate force and organize space. Though studied to some extent by a host of fields, the study of the actin cytoskeleton itself is an area with many questions left to be answered, such as how cells disassemble actin in the presence of large concentrations of both monomeric and polymeric actin, how apparently very stable actin structures can be disassembled, and what role actin plays in the nucleus and how this role differs from cytosolic actin dynamics. Using a biochemical reconstitution approach, we set out to find one or more factors that conferred actin disassembly activity to the known actin disassembly factors. Once identified as cyclase associated protein (CAP), we next studied the properties of this factor focusing on its interactions with actin and other actin disassembly factors including cofilin, coronin, and AIP1. We discovered that CAP has a complimentary yet synergistic relationship with cofilin, a partially redundant relationship with coronin, and that CAP can act as an independent actin disassembly factor at low pH. While CAP was a known actin interacting protein, none of these findings were known to the field before our work was published. After an introduction and summary of the state of the field as it was when we started, Chapter 2 begins with the initial characterization of CAP and our efforts to determine its function. We soon realized that the field was mistaken about the role of CAP as an accessory protein not truly involved in actin disassembly, and we showed that CAP accelerates cofilin, coronin and AIP1-mediated actin depolymerization. We then demonstrated a partial redundancy to coronin but showed that the underlying mechanism of CAP-mediated actin disassembly was distinct from that of coronin. Next we set out to discover what the precise role of CAP was through two similar but distinct lines of experiments. In Chapter 3 we study CAP using similar methodologies but with single actin filaments instead of the branched actin networks in the actin comet tails formed by L monocytogenes. This allowed us to more precisely control the experimental conditions while also giving information of single filament off-rates and allowed us to determine the interaction between CAP, cofilin and pH. In Chapter 4 we continue to study branched actin networks formed by L monocytogenese, but formed under defined conditions without any cell extract. This work was designed to allow us to determine whether there might be activities of CAP which were geometrically dependent, such as any activity confined to branch points. What we found was that actin filaments built with ena/vasp-like protein (EVL) were more susceptible to CAP disassembly. Finally in Chapter 5 we offer a few concluding remarks about the state of the field and the recurrent sense of premature accomplishment that it is prone to

Brain temperature and its fundamental properties: a review for clinical neuroscientists

Brain temperature, as an independent therapeutic target variable, has received increasingly intense clinical attention. To date, brain hypothermia represents the most potent neuroprotectant in laboratory studies. Although the impact of brain temperature is prevalent in a number of common human diseases including: head trauma, stroke, multiple sclerosis, epilepsy, mood disorders, headaches, and neurodegenerative disorders, it is evident and well recognized that the therapeutic application of induced hypothermia is limited to a few highly selected clinical conditions such as cardiac arrest and hypoxic ischemic neonatal encephalopathy. Efforts to understand the fundamental aspects of brain temperature regulation are therefore critical for the development of safe, effective, and pragmatic clinical treatments for patients with brain injuries. Although centrally-mediated mechanisms to maintain a stable body temperature are relatively well established, very little is clinically known about brain temperature's spatial and temporal distribution, its physiological and pathological fluctuations, and the mechanism underlying brain thermal homeostasis. The human brain, a metabolically “expensive” organ with intense heat production, is sensitive to fluctuations in temperature with regards to its functional activity and energy efficiency. In this review, we discuss several critical aspects concerning the fundamental properties of brain temperature from a clinical perspective

Message Journal, Issue 5: COVID-19 SPECIAL ISSUE Capturing visual insights, thoughts and reflections on 2020/21 and beyond...

If there is a theme running through the Message Covid-19 special issue, it is one of caring. Of our own and others’ resilience and wellbeing, of friendship and community, of students, practitioners and their futures, of social justice, equality and of doing the right thing. The veins of designing with care run through the edition, wide and deep. It captures, not designers as heroes, but those with humble views, exposing the need to understand a diversity of perspectives when trying to comprehend the complexity that Covid-19 continues to generate. As graphic designers, illustrators and visual communicators, contributors have created, documented, written, visualised, reflected, shared, connected and co-created, designed for good causes and re-defined what it is to be a student, an academic and a designer during the pandemic. This poignant period in time has driven us, through isolation, towards new rules of living, and new ways of working; to see and map the world in a different light. A light that is uncertain, disjointed, and constantly being redefined. This Message issue captures responses from the graphic communication design community in their raw state, to allow contributors to communicate their experiences through both their written and visual voice. Thus, the reader can discern as much from the words as the design and visualisations. Through this issue a substantial number of contributions have focused on personal reflection, isolation, fear, anxiety and wellbeing, as well as reaching out to community, making connections and collaborating. This was not surprising in a world in which connection with others has often been remote, and where ‘normal’ social structures of support and care have been broken down. We also gain insight into those who are using graphic communication design to inspire and capture new ways of teaching and learning, developing themselves as designers, educators, and activists, responding to social justice and to do good; gaining greater insight into society, government actions and conspiracy. Introduction: Victoria Squire - Coping with Covid: Community, connection and collaboration: James Alexander & Carole Evans, Meg Davies, Matthew Frame, Chae Ho Lee, Alma Hoffmann, Holly K. Kaufman-Hill, Joshua Korenblat, Warren Lehrer, Christine Lhowe, Sara Nesteruk, Cat Normoyle & Jessica Teague, Kyuha Shim. - Coping with Covid: Isolation, wellbeing and hope: Sadia Abdisalam, Tom Ayling, Jessica Barness, Megan Culliford, Stephanie Cunningham, Sofija Gvozdeva, Hedzlynn Kamaruzzaman, Merle Karp, Erica V. P. Lewis, Kelly Salchow Macarthur, Steven McCarthy, Shelly Mayers, Elizabeth Shefrin, Angelica Sibrian, David Smart, Ane Thon Knutsen, Isobel Thomas, Darryl Westley. - Coping with Covid: Pedagogy, teaching and learning: Bernard J Canniffe, Subir Dey, Aaron Ganci, Elizabeth Herrmann, John Kilburn, Paul Nini, Emily Osborne, Gianni Sinni & Irene Sgarro, Dave Wood, Helena Gregory, Colin Raeburn & Jackie Malcolm. - Coping with Covid: Social justice, activism and doing good: Class Action Collective, Xinyi Li, Matt Soar, Junie Tang, Lisa Winstanley. - Coping with Covid: Society, control and conspiracy: Diana Bîrhală, Maria Borțoi, Patti Capaldi, Tânia A. Cardoso, Peter Gibbons, Bianca Milea, Rebecca Tegtmeyer, Danne Wo

THERMAL REGULATION OF THE BRAIN -AN ANATOMICAL AND PHYSIOLOGICAL REVIEW FOR CLINICAL NEUROSCIENTISTS

Humans, like all mammals and birds, maintain a nearly constant core body temperature (36 -37.5°C) over a wide range of environmental conditions and are thus referred to as endotherms. The evolution of the brain and its supporting structures in mammals and birds coincided with this development of endothermy. Despite the recognition that a more evolved and complicated brain with all of its temperature-dependent cerebral circuitry and neuronal processes would require more sophisticated thermal control mechanisms, the current understanding of brain temperature regulation remains limited. To optimize the development and maintenance of the brain in health and to accelerate its healing and restoration in illness, focused and committed efforts are much needed to advance the fundamental understanding of brain temperature. In order to effectively study and examine brain temperature regulation, it is critical to first understand the relevant anatomical and physiological properties in the head-neck regions