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One Vibe Africa

During the month of February, Kijiji Night 2020 will mark One Vibe Africa's 6th year partnering with the Seattle Art Museum to produce a free-to-the-public evening dedicated to celebrating the African Diaspora. On February 6, 2020, the spirit of an African village will be brought to life at SAM, 1300 1st Avenue from 5:00-9:00pm, through live hip-hop and traditional African musical performances, storytelling, poetry, and fresh food provided by Cafe Avole.

Friends of King Donut

A community mural will be installed at King Donuts, featuring four 6.5’ x 6’ wooden fence panels designed by a local artist. Each panel will be painted by Rainier Beach youth and community members using a color-by-number system, creating an inclusive and collaborative art piece. The mural’s design will be informed by a community event where local youth and residents contribute ideas and concept art. These events include art stations, food, and entertainment to support broad community participation and creative input. The anticipated project completion date is November 30, 2025.

Asian Americans for Arts Activism - A4A

Asian Americans for Arts Activism - A4A will host a free three-day celebration of Asian Pacific Islander American heritage month. The first event will be on May 26, 2018 from 11am - 1pm at Wing Luke Museum located at 719 S King St. The second will be on May 27, 2018 from 11am - 1pm at Seattle Public Library located at 1000 4th Ave. The final event will be on May 28, 2018 from 11am - 1pm at Royal Esquire Club located at 5016 Rainier Ave S. The events will feature workshops, film, art, and food.

Kresge Foundation

Supports programs that expand opportunity for low-income people in American cities. Focus areas: arts, education, environment, health, and human services.

La Crosse Community Foundation

La Crosse Community Foundation ($75M in assets) supports nonprofits in WI through grants focused on education, community development, health, arts. Awards range from $1,000 to $25,000.

Lafayette PTA

The Lafayette PTA will create a free, non-denominational Winter Light Festival on the Lafayette School playground for the entire West Seattle community to enjoy December 5th and 6th from 5-7 pm at 2645 California Avenue SW. The displays will be wheelchair and stroller accessible. Free cookies, hot cocoa, and non -religious music will be provided. We want our student's light designs and art to be celebrated by our entire community. This project will be completed by January 31, 2020.

Friends of Lake City Youth at Coyote North

The Friends of Lake City Youth at Coyote North want to engage the Lake City community in activating a youth-centered creative space at 12325 Lake City Way NE. This year long project and will do outreach efforts throughout the year to bring together Lake City families from all races, cultures, and backgrounds through open houses, community dinners, exhibits, performances, and free youth arts programs, culminating in a youth-led community celebration.

Lancaster County Community Foundation

Lancaster County Community Foundation ($150M in assets) supports nonprofits in PA through grants focused on education, arts, community development, health. Awards range from $1,000 to $50,000.

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary/Abstract: Long-acting antiretroviral therapy (LA-ART) represents a transformative advance in HIV treatment, including for persons with HIV (PWH) who have HIV viremia. However, LA-ART regimens lack activity against hepatitis B virus (HBV), creating a vulnerability for PWH with prior HBV exposure or HBV non-immunity. Discontinuation of HBV-active antiretrovirals during transitions to LA-ART can lead to HBV reactivation or new HBV infection, resulting in hepatitis flares and death. Despite these risks, there is substantial variability in reported incidence across populations, and most available data derive from observational cohorts or case-based series. Consequently, the incidence, predictors, and biological mechanisms of HBV reactivation and incident infection in the context of LA-ART remain poorly defined, limiting safe implementation of these therapies in the United States and globally. Similarly, patient and provider knowledge, acceptability, and preferences regarding HBV screening and monitoring during LA-ART are not well understood, and the optimal cost-effective approach to HBV screening and monitoring during LA-ART transition is unknown. This project leverages the ACTG LANCET (A5433) clinical trial, which randomizes PWH with viremia to standard-of-care tenofovir/lamivudine/dolutegravir or LA-ART cabotegravir and rilpivirine. This multidisciplinary study integrates clinical and virologic investigations with complementary behavioral science studies and cost- effectiveness analyses. Aim 1 will quantify the incidence, predictors, and clinical consequences of new and reactivation HBV among PWH transitioning to LA-ART and will evaluate novel virologic and serologic biomarkers, including quantitative HBsAg and HBV RNA, to identify early predictors of risk. Aim 2 will assess patient and provider knowledge, preferences, and decision-making around HBV screening, monitoring, and management during LA-ART using surveys and in-depth interviews, and will develop practical tools to support real-world implementation, both using data from A5433 and a separate UCLA and UCSD prospective mixed- methods survey study. Aim 3 will define cost-effective strategies for HBV screening and monitoring during LA- ART transition in the US, Brazil, and Botswana. The results will inform clinical guidelines by defining the true incidence of new and reactivation HBV, establishing evidence-based approaches to HBV screening and monitoring, and identifying the most cost-effective strategies to protect liver health during HIV LA-ART.

NINDS - National Institute of Neurological Disorders and Stroke

Project Summary/Abstract Epilepsy can be genetic. In many cases, genetic epilepsies present with severe drug-resistant seizures. Comorbid conditions in these patients can include cognitive deficit, impaired communication, autism, mood disorders, and significant developmental delay. Although de novo single gene mutations were identified for many genetic epilepsies, our overall understanding of these conditions remains limited. We generated a library of single-gene mutant zebrafish models and used sensitive electrophysiology screening to uncover epilepsy phenotypes. Several zebrafish models exhibiting spontaneous electrographic seizure activity were identified. Here we propose studies using models for SCN1A and ARX mutations. These vertebrate models recapitulate epilepsy endophenotypes and represent a sub-category of epileptic encephalopathies associated with interneuron dysfunction or loss, respectively. As an experimental model, zebrafish (Danio rerio) possess tremendous potential to advance our understanding of brain networks at a scale not possible with rodent models. Building on our extensive experience developing zebrafish models and technologies for epilepsy research, two specific aims utilizing scn1a and arxa mutants are proposed: (i) to analyze brain-wide seizure dynamics in epileptic zebrafish and (ii) to understand how interneurons regulate seizure dynamics in epileptic zebrafish. Techniques will include fast volumetric calcium imaging, multiplexed hybridization chain reaction protocols, and in vivo electrophysiology. This research is significant because it merges state-of-the-art calcium imaging approaches with clinically relevant zebrafish models, to provide fundamental insights into these debilitating conditions.

Lauder Foundation

Funds arts, culture, education, and Jewish community programs globally.

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary The AIDS Clinical Trials Group (ACTG) has been at the forefront of clinical research to advance HIV therapeutics and improve the health of people living with HIV/AIDS for 30 years. Rigorous scientific research conducted by the ACTG has laid the cornerstones for current HIV treatment guidelines. In this application for the competitive renewal of the ACTG we propose a transformative research agenda that draws on an international consortium of leading clinical and laboratory HIV investigators in collaboration with a world-class Statistics and Data Management Center to design and conduct innovative interventional clinical trials that will significantly reduce the global burden of disease due to HIV, TB and hepatitis B. The Leadership and Operations Center (LOC) provides scientific leadership and fiscal and organizational management of the ACTG. The ACTG Executive Committee (AEC) will serve as the overarching governing body of the network. The AEC is guided by an Executive Management Committee that includes the Network Chairs, Chief Quality Officer and the Chairs of the Laboratory and Statistical and Data Management Centers. Transformative Science Groups will oversee the development and execution of the ACTG research agenda, which will be coordinated and prioritized by the Scientific Agenda Steering Committee (SASC). Protocol development, implementation, training and network evaluation will be facilitated by the Network Clinical Core at Social & Scientific Systems, Inc. The LOC financial management group (Admin Core) at the University of California, Los Angeles will oversee resource management and protocol fund distribution at the direction of the AEC. The LOC will assure the engagement of Community in all aspects of the ACTG, and will coordinate communication between all three components of the network. Specific aims of this proposal include: 1) Identify interventions to reduce HIV reservoirs and control HIV replication in the absence of ART; 2) Test novel and durable interventions targeting HIV infection; 3) Improve the treatment and prevention of drug sensitive and drug resistant tuberculosis; 4) Prevent or improve the treatment of HIV-related non-infectious co-morbidities and evaluate strategies to cure hepatitis B virus infection in people with and without HIV.

U.S. National Science Foundation

NSF s goal for high performance computing (HPC) in the period 2006-2011 is to enable petascale science and engineering through the deployment and support of a world-class HPC environment comprising the most capable combination of HPC assets available to the academic community. The petascale HPC environment will enable investigations of computationally challenging problems that require computing systems capable of delivering sustained performance approaching 1015 floating point operations per second (petaflops) on real applications, that consume large amounts of memory, and/or that work with very large data sets. Among other things, researchers will be able to perform simulations that are intrinsically multi-scale or that involve the simultaneous interaction of multiple processes. HPC Resource Providers - those organizations willing to acquire, deploy and operate HPC systems in service to the broad science and engineering research and education community - play a key role in the provision and support of a national HPC environment. With this solicitation, NSF requests proposals from organizations, or groups of organizations, willing to serve as a petascale HPC Resource Provider, and who propose to acquire and deploy a new, state-of-the-art, petascale HPC system. A competitive, petascale HPC system will: *Enable researchers to work on a range of computationally-challenging science and engineering applications at the frontiers of research; *Incorporate reliable, robust system software essential to optimal sustained performance; *Provide a high degree of stability and usability; and, *Function as a community-driven resource that actively engages the research and education communities in petascale science and engineering. A robust and effective HPC acquisition process, driven by the requirements of the science and engineering research and education community, is one of the key elements of NSF s HPC strategy. Accordingly, the desired capabilities of the system to be acquired are defined in terms of performance on model problems.

Lee Foundation

One of Singapore's largest philanthropic foundations supporting education, welfare, arts, and healthcare.

OD - NIH Office of the Director

Project Summary/Abstract We are requesting a Leica Stellaris 8 two-photon (2P) and conventional confocal hybrid microscope system. This instrument is required to maintain and expand biomedical research programs at the University of Montana (UM). It will be integrated into the BioSpectroscopy Core Research Laboratory (BCRL), which is a part of the NIH CoBRE funded Center for Biomolecular Structure and Dynamics (CBSD) at UM. The proposed instrument will be available to users at UM along with external users at regional institutions. This microscope will advance imaging in the life sciences, expanding the capability to detect tissue-specific features related to disease and development. The BCRL currently provides access to a Zeiss 880 laser scanning confocal microscope. However, this instrument has been in service since 2016 and is not currently meeting the needs of BCRL users. One area of deficiency is limited fluorescence lifetime imaging microscopy (FLIM) capabilities of the Zeiss 880. While the Zeiss 880 can perform FLIM, it relies on the integration of PicoQuant parts and software. This results in the acquisition of FLIM images at 50% below Nyquist resolution limit, the need to manually change and/or purchase bandpass filters to adjust the detected emission window, and outdated functional integration between confocal and FLIM modules. The proposed Leica Stellaris 8 offers an "all-in-one" FLIM setup without the need for third party equipment and software. Leica HyD detectors come equipped with variable bandpass filters and dichroics, reducing user maintenance and the need to purchase additional filters. Another critical need of BCRL users is two-photon (2P) microscopy capability, which is not currently available at UM. Our major users plan to image tissue features defined by second harmonic generation, perform 2P FLIM, or image deep within tissues. These needs are only met by a 2P microscope. Imaging of murine lung, murine brain tissue, and Drosophila brains will be enhanced with the acquisition of the proposed microscope. In addition, several technical innovations in conventional confocal microscopy will be advantageous to our users. These include but are not limited to faster acquisition, on-the-fly deconvolution, near-IR detection capabilities, spectral unmixing, and background removal. Thus, a combined 2P and confocal system is sought to meet current user needs, attract new users, and provide state-of-the-art equipment to support NIH funded research. The acquisition of the proposed instrument will advance the research programs of eight NIH-funded major users and two users funded through other sources.

Leschi Community Council

The Leschi Community Council (LCC) will be hosting the Leschi Art Walk along Lakeside Avenue in Seattle's Leschi Community on Sept. 14 from 11am-4pm. Our goal is to bring the community together with music and activities for children, as well as provide a venue for artists to display their creations. We also want to bring in people from across Seattle to increase familiarity with the businesses along the lakefront. The event is free and open to the public.

Leschi Community Council

The Leschi Community Council will be hosting the Leschi Community Art Walk, located at 140 Lakeside Ave on September 10, from 11am-4pm. The Art Walk goals is to bring community together, provide a venue for the artist to display their creations and to bring people from across Seattle to increase familiarity about the businesses along the lakefront. The event is free and open to the public.

Friends of Art on Pier 86

Friends of Art on Pier 86 (FAP86) will project illuminated art onto the side of a building at Pier 86 in cooperation with the Port of Seattle. A pilot image or series of images will be projected for three months during the first half of 2018, and different art will be projected for a similar period at the end of 2018. They will do a call for artists, lead community workshops for input into art design, host opening events, and conduct community feedback surveys.

NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases

Project Summary/Abstract Interorgan communication between the brain and peripheral tissues maintains a range of adaptive responses that can degrade with aging. Using mouse models, we found a powerful neural circuit that simultaneously motivates spontaneous activity and overrides spinal reflexes that control bladder and colonic function. Our preliminary findings show a strong direct neural circuit between estrogen-responsive neurons in the hypothalamus and the major micturition center in the hindbrain that controls urination, the Pontine Micturition Center (PMC) or Barrington’s nucleus (BAR). When activated, this VMHvl-BAR monosynaptic circuit blocks all voiding, even when animals have been pre-loaded with saline; when inhibited, urine release increases. Similarly, when a glass bead is inserted into the colon, excretion of this pellet takes up to fifteen times longer (20 minutes versus 5 hours) if chemogenetics is used to activate this neurocircuit. In vivo cystometry results confirm the potency of this hypothalamic-hindbrain circuit in modulating urine and fecal release. Here, we will define how neurons in BAR override normal spinal reflexes in the pelvic region. We outline three independent aims to: 1) identify the molecular nature of the inhibitory neurons in BAR responsible for this change in urinary and colon function and map projections from BAR to the spinal cord controlling the bladder or colon, 2) determine the sufficiency of VMHvl-BAR circuity components in urine release, and finally, 3) determine the initiating signals in the hypothalamus that control this voiding and defecation neurocircuit. This last aim will bring us closer to translating our preclinical research to human health. Our research program adds to emerging work on brain-body physiology to advance strategies for improving health and blends the team’s expertise in neuroendocrinology and neurocircuits. We are using state-of-the-art methods to pursue hypothesis-driven questions to decode a robust neuroendocrine circuit that controls two essential processes—urination and defecation. Both functions degrade with aging, especially in older women. Eventually, we wish to translate these preclinical studies to mitigate the loss of pelvic control in the older adult US population.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Innovative strategies are needed to address the unique challenges faced by women living with HIV (WLHIV) in West Africa. Among the 5.1 million people living with HIV (PLHIV) in West and Central Africa in 2023, 65% were adolescent girls and women. Among PLHIV in the region, 81% knew their HIV status, 76% were receiving antiretroviral therapy (ART), and 70% had suppressed viral loads. Addressing the social and structural barriers that disproportionally impact women is critical to achieving the 95-95-95 targets and ending the HIV epidemic. Our previous work in Senegal, West Africa has shown that the majority of WLHIV are food insecure and that food insecurity is associated with poor HIV outcomes, including loss to follow-up, poor adherence to ART, and virologic failure. The high prevalence of food insecurity among WLHIV in Senegal and its role as a driver of poor outcomes across the HIV care cascade, suggest that strategies to address food insecurity are essential to interrupting transmission, improving quality of life, and preventing mortality. The Casamance region, located in the south of Senegal, has been the most severely affected by the HIV epidemic and has the highest prevalence of food insecurity in the country. In collaboration with our longstanding partners at the NGO DIG (“Development in Gardening”), the Service des Maladies Infectieuses et Tropical-CHNU de Fann, and the Région Médicale de Ziguinchor, we recently conducted an NIH funded pilot study to evaluate the experience and impact of a multisectoral nutrition-sensitive agricultural intervention among WLHIV in the Casamance. The findings from our pilot study suggest that participation in the intervention is associated with improvements in food security, virologic suppression, and mental health. In the proposed study, we will leverage our longstanding partnerships in Senegal and build upon our findings to conduct a cluster randomized trial to evaluate the impact of a multisectoral nutrition-sensitive agricultural (MNSA) intervention on HIV outcomes among women in the Casamance region. The AIMS of this study are, AIM 1. Determine the impact of a MNSA intervention on HIV outcomes among WLHIV in Senegal, AIM 2. Determine the mechanisms by which the MNSA intervention improves HIV outcomes among WLHIV in Senegal, Aim 2a. Determine the impact of the MNSA intervention on food security, dietary diversity, and nutritional status, Aim 2b. Determine the impact of the MNSA intervention on mental health outcomes and empowerment, and AIM 3. Determine the costs, cost-effectiveness, scalability, and sustainability of the MNSA intervention.

NIH

Project Summary Background and Innovation: Glucagon has long been recognized as an insulin counterregulatory hormone. However, more recent studies have revealed that it also activates glucagon-like peptide-1 receptors (GLP1R) on beta cells to enhance glucose-dependent insulin secretion. Harnessing glucagon for diabetes therapy has been challenging because of its opposing hyperglycemic and hypoglycemic effects in the liver and islet. Remarkably, we have discovered a transcriptional network controlled by BCL6 in the liver which causes a unique form of selective glucagon resistance and confers favorable anti-diabetic effects in both the liver and islet. Our first aim will elucidate the impact of BCL6 on glucagon action and metabolism in the liver. Our second aim will determine the inter-organ ramifications of this liver pathway on islet signaling and insulin secretion. Finally, in our third aim we will test a liver specific Bcl6 knockdown as a therapeutic for type 2 diabetes mellitus. Our study will elucidate this previously unknown liver pathway using a broad combination of biochemical assays, epigenetic and gene expression analysis, and physiologic testing with unique mouse models and primary cells, including both gain- and combinatorial loss-of-function genetic strategies to reveal interorgan communication. Further, we will use state-of-the-art hepatocyte-directed antisense oligonucleotides (ASOs) for preclinical testing to establish the benefits of targeting BCL6 for diabetes and obesity therapy. Collectively, these experiments will provide deep mechanistic and physiologic understanding of glucagon and therapeutic manipulation of glucagon signaling, setting the stage for clinical development and testing of analogous hepatocyte-directed therapy for humans. Significance and Impact to Veterans Healthcare: Type 2 diabetes mellitus afflicts 25% of Veterans, and hyperglycemia and diabetes-related complications remain inadequately controlled with current therapies. Our findings will elucidate a new target for treating type 2 diabetes mellitus and obesity-related disease. Exploiting this target will enable therapies to leverage both the benefits of glucagon blockade in the liver and glucagon agonism in the islet to improve glycemic control. Moreover, we will establish the efficacy of targeted nucleic acid-based therapy to specifically exploit the liver BCL6 pathway for therapy of type 2 diabetes mellitus in pre-clinical models. Path to translation/implementation: The work in this proposal will be foundational in establishing BCL6 as a new target for diabetes. We will test antisense oligonucleotides targeted specifically to hepatocyte BCL6 in mice. Success in our pre-clinical model can then be advanced for human translation by adapting the antisense oligonucleotides to knockdown the human BCL6 ortholog for future clinical testing in humans with type 2 diabetes mellitus.

Library of Congress

This funding opportunity is authorized under the Legislative Branch Appropriations Act of 2023 (Pub. L. 117-389 (H.R. 8237)), subject to availability of funding. The resulting awards will be subject to the Library of Congress Regulation (LCR) 7-310. In addition, while the Library, as a legislative agency, is not subject to 2 CFR 200 Uniform Administrative Requirements, Costs Principles and Audit Requirements for Federal Awards, the resulting awards will be subject to selective provisions of 2 CFR 200 as determined by the Library and indicated in this NOFO. About the Library of Congress The Library of Congress is the largest library in the world, with millions of books, films and video, audio recordings, photographs, newspapers, maps and manuscripts in its collections. The Library is the main research arm of the U.S. Congress. It is the nation s oldest federal cultural institution. The Library s mission is to engage, inspire, and inform Congress and the American people with a universal and enduring source of knowledge and creativity. About the Teaching with Primary Sources Program (TPS) The Teaching with Primary Sources program (www.loc.gov/teachers) has been the Library of Congress s premier educational grant program since 2006. The goals of the program have included providing instructional materials, tools, education and professional development that enhance teachers ability to integrate digitized primary sources from the Library of Congress into instruction that builds student literacy, critical thinking skills, content knowledge and ability to conduct original research. Since the establishment of the Center for Learning, Literacy and Engagement in 2018, and the release of the Library s 2024-2028 Strategic Plan, the TPS goals both influence and reflect the Library s broader outreach goals. About the Lewis-Houghton Civics and Democracy Initiative (LHI) Named in honor of Rep. John R. Lewis (D-GA) and Rep. Amo Houghton (R-NY), the Lewis-Houghton Civics and Democracy Initiative (LHI) is included under the Teaching with Primary Sources (TPS) program. In the joint explanatory statement for the Legislative Branch Appropriations Act, 2023, Congress established the Lewis-Houghton Civics and Democracy Initiative and appropriated funds to the Library of Congress to award grants to eligible organizations within the United States (U.S.) and its territories to develop digitally-enabled, creative arts-driven projects focused on using the digitized primary sources of the Library of Congress to teach history, civics and/or democracy. More information and a description of past LHI-funded projects can be found at: https://www.loc.gov/programs/teachers/about-this-program/teaching-with-primary-sources-partner-program/lewis-houghton/. TPS Educational Consortium Grantee organizations become members of the TPS Educational Consortium. They include a wide variety of educational organizations including school districts, libraries, cultural institutions, universities and technology firms that have received Library funding to deliver teacher professional development, create teaching materials and develop apps and online interactives, based on Library of Congress materials. TPS Consortium members are valued as Connectors who help the Library achieve its vision of connecting to all Americans. TPS Consortium members extend the Library s reach by connecting hundreds of thousands of American educators and learners, including K-12 teachers and their students, to Library of Congress methods and materials. Consortium members collaborate, co-create, share ideas, network and actively participate as an educational community. Purpose The purpose of this notice is for the Library of Congress to solicit project proposals from eligible organizations and select awardee organizations that will design and implement educational projects in which the Library s music or creative arts-related digitized primary sources and other online materials are central to teaching and learning about history, civics, and/or democracy. Awards made under Lewis-Houghton Civics and Democracy Initiative must include rights-free materials from the Library s music or creative arts digital collections, to develop curriculum, teaching materials, educational programs, pedagogical approaches, and/or other tools for history, civic and democracy instruction targeted toward middle and high school educators and learners. LHI awards should center on inquiry-driven analysis of primary sources, build learners civic skills and foster participation in our nation s democracy. In addition to highlighting primary sources from the Library s collections of music, dance, theater, visual arts, folk arts, film, photography, book arts, arts and literary manuscripts, and/or other creative arts, proposals may also include the use of arts-based pedagogies and other creative approaches. All proposals must expand the body of innovative strategies, tools, and materials for meaningful teaching and learning with Library of Congress materials. The focus of LHI awards includes the design of educational projects using Library of Congress materials for use in and outside of formal classroom settings. In addition to using Library primary sources to deliver history, civics, and/or democracy learning experiences integrating the arts, projects must address demonstrated educational needs of specific recipient populations and provide solutions that standard practice, documented experience, or research suggest would be effective. Organizations that receive LHI awards make up a subset of the TPS Educational Consortium whose work spans areas of interest including but not limited to arts integration, civics education, multimodal learning, and teaching with audiovisual primary sources. Funded projects will support the Library s mission to use its collections to connect with all Americans, including those representing multiple communities, beliefs and endeavors, to engage, inspire and inform Congress and the American people with a universal and enduring source of knowledge and creativity. Projects must use the Library s digital collections for one or more of the following approaches: a) Deliver educational programming to various categories of educators and learners in secondary education (middle and high school); b) Create and distribute educational materials or tools for teaching specific content in history, civics, and/or democracy; c) Convene meetings of like organizations to devise strategies for furthering common learning and teaching goals with Library of Congress materials related to music and/or the arts; and/or d) Conduct research with significant practitioner involvement that investigates the impact of incorporating Library of Congress music and/or creative arts collections into history, civics, and/or democracy educational initiatives. Questions and Answers General Questions and Answers: All questions relating to this Notice must be submitted via email to tps-grant@loc.gov no later than the date stated in Section B of the Notice ( General Questions Submission Deadline ). The subject of each e-mail must read as follows: Notice 030ADV26R0050 Lewis-Houghton Initiative New Awards 2027. Answers will be provided in a Q&A document uploaded to grants.gov. Questions received after the deadline(s) stated in Section B above may not be answered. Technical Questions Submission: Applicants experiencing problems with submitting proposals can request technical assistance until the date specified in Section B above ( Technical Questions Submission Deadline ).

Velocity Dance Center

A vibrant week of outdoor dance performances, large-scale art installations, and LGBTQ+-led conversations in Capitol Hill over Labor Day weekend to promote an inclusive understanding of gender, parenting, and queer lineage. Additionally, organizers will host free BIPOC-led queer parent convenings to build community support networks for queer Seattle parents. Queer and trans family resources will be available in person and online to all participants and project attendees.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Atherosclerotic cardiovascular disease (ASCVD) is the second leading cause of non-AIDS-related mortality among people living with human immunodeficiency virus (HIV) (PLWH). The number of PLWH is continuously growing due to the viral suppression and life-extending benefits of available antiretroviral therapy (ART). However, the PLWH, even on effective ART with undetectable viral loads as well as elite HIV controllers who are ART-naïve and aviremic, exhibit sustained systemic inflammation and accelerated atherogenesis. Accumulated evidence suggests an important role of persistent macrophage (Mɸ) activation in controlled HIV- induced ASCVD and significant transcriptional heterogeneity among Mɸs within atherosclerotic lesions. Moreover, recent research indicates the involvement of Mɸ-derived extracellular vesicles in regulating neighboring non-HIV-infected Mɸ lipid metabolism, phenotype, foam cell formation, and atherogenesis. However, the precise molecular mechanisms linking controlled HIV infection to Mɸ activation and accelerated atherosclerosis remain poorly understood. Our preliminary experiments utilizing an experimental EcoHIV/NDK model, which mimics the physiological conditions of aviremic patients on effective ART, demonstrate increased atherosclerosis following infection. Furthermore, treatment with conditioned media (CM) collected from HIV- infected Mɸs induces expression of leucine-rich repeat-containing GPCR (LGR) 4 at both transcription and translational levels in non-infected murine primary Mɸs. Notably, Lgr4 upregulation induced by HIV-infected Mɸ CM was significantly higher than that promoted by oxidized LDL, a well-known atherogenic agent. Consistently, LGR4 levels are elevated in human atherosclerotic aortic segments compared with non-atherosclerotic tissue, and in atherosclerotic lesional Mɸs of EcoHIV-infected mice. Additionally, CM-treated Mɸs exhibit increased lipid accumulation (foam cell formation), augmented inflammation, and impaired efferocytosis. Nevertheless, the role of Mɸ Lgr4 in regulating HIV-regulated efferocytic potential, inflammation, and atherosclerosis is unknown. Based on these findings, we hypothesize that controlled HIV infection accelerates atherosclerosis via Mɸ LGR4- mediated signaling. This hypothesis will be tested with the two independent specific aims investigating whether (1) LGR4 mediates HIV-regulated Mɸ foam cell formation and efferocytic capacity, and (2) controlled HIV infection contributes to atherosclerosis via Mɸ LGR4-mediated signaling. Myeloid-cell specific Lgr4-deficient mice, an LGR4-signaling inhibitory peptide, unbiased single-cell RNA sequencing, and atherosclerotic lesion analysis will be employed to test the hypothesis. The successful completion of the proposed studies will provide novel insights into the mechanisms governing accelerated atherosclerosis in aviremic PLWH and identify novel therapeutic targets. To ensure the success of the proposed studies, we have assembled a multidisciplinary team comprising a collaborator and consultants, and are well-positioned to have all the required key resources.