PublicationThe P2X7 Receptor in Microglial Cells Modulates the Endolysosomal Axis, Autophagy, and Phagocytosis(2021-03-15) Campagno, Keith E.; Mitchell, Claire H.Microglial cells regulate neural homeostasis by coordinating both immune responses and clearance of debris, and the P2X7 receptor for extracellular ATP plays a central role in both functions. The P2X7 receptor is primarily known in microglial cells for its immune signaling and NLRP3 inflammasome activation. However, the receptor also affects the clearance of extracellular and intracellular debris through modifications of lysosomal function, phagocytosis, and autophagy. In the absence of an agonist, the P2X7 receptor acts as a scavenger receptor to phagocytose material. Transient receptor stimulation induces autophagy and increases LC3-II levels, likely through calcium-dependent phosphorylation of AMPK, and activates microglia to an M1 or mixed M1/M2 state. We show an increased expression of Nos2 and Tnfa and a decreased expression of Chil3 (YM1) from primary cultures of brain microglia exposed to high levels of ATP. Sustained stimulation can reduce lysosomal function in microglia by increasing lysosomal pH and slowing autophagosome-lysosome fusion. P2X7 receptor stimulation can also cause lysosomal leakage, and the subsequent rise in cytoplasmic cathepsin B activates the NLRP3 inflammasome leading to caspase-1 cleavage and IL-1β maturation and release. Support for P2X7 receptor activation of the inflammasome following lysosomal leakage comes from data on primary microglia showing IL-1β release following receptor stimulation is inhibited by cathepsin B blocker CA-074. This pathway bridges endolysosomal and inflammatory roles and may provide a key mechanism for the increased inflammation found in age-dependent neurodegenerations characterized by excessive lysosomal accumulations. Regardless of whether the inflammasome is activated via this lysosomal leakage or the better-known K+-efflux pathway, the inflammatory impact of P2X7 receptor stimulation is balanced between the autophagic reduction of inflammasome components and their increase following P2X7-mediated priming. In summary, the P2X7 receptor modulates clearance of extracellular debris by microglial cells and mediates lysosomal damage that can activate the NLRP3 inflammasome. A better understanding of how the P2X7 receptor alters phagocytosis, lysosomal health, inflammation, and autophagy can lead to therapies that balance the inflammatory and clearance roles of microglial cells. © Copyright © 2021 Campagno and Mitchell. PublicationThe Impact of Dental Implant Surface Modifications on Osseointegration and Biofilm Formation(2021-04-02) Kligman, Stefanie; Ren, Zhi; Chung, Chun-Hsi; Perillo, Michael Angelo; Chang, Yu-Cheng; Koo, Hyun; Zheng, Zhong; Li, ChenshuangImplant surface design has evolved to meet oral rehabilitation challenges in both healthy and compromised bone. For example, to conquer the most common dental implant-related complications, peri-implantitis, and subsequent implant loss, implant surfaces have been modified to introduce desired properties to a dental implant and thus increase the implant success rate and expand their indications. Until now, a diversity of implant surface modifications, including different physical, chemical, and biological techniques, have been applied to a broad range of materials, such as titanium, zirconia, and polyether ether ketone, to achieve these goals. Ideal modifications enhance the interaction between the implant’s surface and its surrounding bone which will facilitate osseointegration while minimizing the bacterial colonization to reduce the risk of biofilm formation. This review article aims to comprehensively discuss currently available implant surface modifications commonly used in implantology in terms of their impact on osseointegration and biofilm formation, which is critical for clinicians to choose the most suitable materials to improve the success and survival of implantation. © 2021 by the author. Licensee MDPI, Basel, Switzerland. PublicationExploring sustainable degrowth-based adaptation to climate change-aggravated water insecurity in parts of rural India: A gender relations approach(2022-04-30) Roy Chaudhuri, Nairita; Roy Chaudhuri, NairitaThis article reviews the theoretical concept of ‘sustainable adaptation’ to climate change and water scarcity using a gender-relations approach by answering the following questions: i) What is a sustainable adaptation to climate change? ii) Based on a literature review, how does gender interact with climate change adaptation to water scarcity and droughts in rural India? (iii) How do the concepts of sustainable adaptation, degrowth, and gender relations interact on the ground, pertaining to water justice? The paper argues that climate change adaptation and development goals can harmonize only if they rectify root causes of vulnerabilities. For adaptation actions to yield sustainable outcomes, they need to be embedded in a just degrowth politics that transforms unequal power relations, including gender relations with water. In India, degrowth is about ecological, economic, and social justice that calls for transformation of the economy. This transformation looks into the lifecycle of goods - how goods are produced, composed, assembled, distributed, consumed, and regenerated today; further degrowth strategy explores alternate, just, non-extractive, decolonial, and democratically-led trajectories that sustain the web of life. This paper discusses five interrelated principles of sustainable degrowth-based adaptation that center on community-based notions of water and gender justice. PublicationGood mums: a gender equality perspective on the constructions of the mother in handwashing campaigns(2020-03-10) Cavill, Sue; Huggett, Chelsea; Cavill, Sue; Huggett, ChelseaThe first part of this paper provides a brief overview of the framing of women in hygiene interventions. The following section provides a review of the literature on best practices for handwashing and hygiene, as framed by discourses on the good mother. The goal of this paper is to illustrate how promotional approaches are targeting mothers to change handwashing and hygiene behavior, and to contrast such interventions with the possibility of more gender transformative approaches. We argue that women don’t always implement the handwashing practices they would prefer. This is clearly not due to laziness and thoughtlessness, and it is important to understand the factors women negotiate when making decisions. Furthermore, we argue that by reinforcing, legitimating, and perpetuating the idea of the good mother, hygiene promotion seeks to achieve short-term gains on hygiene at the expense of long-term gains on sustainable behavior change coupled with gender justice and equality. PublicationMenstrual Health and Hygiene Management and WASH in Urban Slums: Gaps in the Evidence and Recommendations(2020-03-10) Goddard, Sarah J.; Sommer, Marni; Goddard, Sarah J.; Sommer, MarniThe rapid urbanization and development of megacities across many low- and middle-income countries creates new challenges in global health; this is particularly true for women and girls who are disproportionately affected by poor urban planning, inadequate sanitation infrastructure, and limited access to water. Urban slums serve to reinforce many gendered inequalities, as reflected in poor sexual and reproductive health outcomes and various other health and wellbeing indicators. Women and adolescent girls in urban slums are particularly vulnerable in relation to their experiences of menstruation, given the limited access they may have to safe, private spaces with water for changing, washing, bathing, and laundering reusable pads, menstrual cloths and pads, and insufficient access to culturally acceptable, adequate disposal mechanisms for used menstrual materials. On-going taboos and stigma around menstruation likely augment these challenges in urban slum contexts; however, there exists limited literature on the intersection of menstrual hygiene management with water and sanitation systems in urban slums in low- and middle-income countries. Through a review of literature, this article seeks to highlight critical interlinkages between urbanization, sanitation, and menstruation, and identify important gaps in the existing menstruation-related evidence base that have implications for the health and wellbeing of adolescent girls and women.