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NIAID - National Institute of Allergy and Infectious Diseases

Abstract The human immunodeficiency virus (HIV) remains as an incurable pandemic pathogen that lacks an effective vaccine. While antiretroviral therapies (ART) can effectively suppress HIV replication, it does not eradicate the virus. As a result, people living with HIV (PLWH) remain vulnerable to AIDS in part due to viral immune evasion strategies. The HIV accessory protein Nef plays a crucial role in this process. Nef enhances viral replication and immune evasion by altering the trafficking and promoting the degradation of immune receptors. One of Nef’s most well characterized functions is the disruption of the major histocompatibility class I (MHC-I) trafficking to target it for lysosomal degradation. This Nef function prevents cytotoxic T lymphocyte (CTL) recognition and clearance of infected cells thereby enabling evasion of the immune response. While some pathways targeted by Nef are well studied, the full breadth of Nef’s host interactions— especially in the context of other HIV accessory proteins— remains poorly understood. One approach to address this gap in knowledge is unbiased proteomic analysis of Nef-host protein interactions. Three prior studies have utilized proteomic approaches to investigate Nef functions. However, their conclusions have been limited by using systems that express Nef in isolation, the use of potentially disruptive affinity tags, and failure to block degradative pathways, utilized by Nef. Our preliminary data as well as the work proposed here address these limitations. In our preliminary studies and proposed aims we will use both T cell lines and primary T cells expressing all HIV accessory proteins (Vif, Vpu, and Vpr, Rev and Tat) and a novel functionally validated tagged Nef protein. Using this system, we identified the Nef interactome in a T cell line in the presence and absence of lysosomal inhibition by TMT-based quantitative proteomics. Furthermore, with our approach we have identified novel Nef binding proteins associated with inflammatory, innate immune response and viral sensing pathways. Subsequent analyses have confirmed these novel interactions in both a T cell line and primary T cells. Based on our strong preliminary data, we will test the overarching hypothesis that novel Nef interacting proteins that have not previously been reported will reveal new pathways targeted by Nef that promote viral pathogenesis. We will evaluate our hypothesis with the following aims. In Aim 1, we will confirm our preliminary data and extend the characterization of the Nef interactome to primary T cells, and we will identify the Nef binding domains responsible for novel Nef-host protein interactions. Furthermore, in Aim 2, we will determine the functional significance of novel Nef interactions with inflammatory and antiviral pathways. The work proposed in this study will provide a complete, unbiased characterization of the Nef interactome as well as reveal pathways that are essential for HIV pathogenesis. Furthermore, these findings hold promise for identifying novel therapeutic targets for HIV infected patients.

OD - NIH Office of the Director

PROJECT SUMMARY/ABSTRACT This proposal requests funds to acquire a LUMICKS C-Trap Dymo300 microscope to support NIH-funded investigators across multiple schools at Vanderbilt University. The C-Trap combines the ability to exert forces on molecules and cells through optical tweezers with the ability to visualize structures through confocal imaging with the sensitivity to detect single molecule fluorescence. The instrument is highly automated and capable of handling complex calibrations and work-flow scripts, facilitating access for a broader scientific community. The instrument also includes a microfluidic laminar flow platform that aids in assay construction and protocol refinement. This microscope will be located within, and maintained by, the Vanderbilt Center on Mechanobiology – an initiative that serves faculty labs within the School of Engineering, the School of Medicine Basic Sciences, and the College of Arts and Sciences. All three schools have provided matching financial commitments that will fully cover the service contract for the instrument. Multiple scientific thematic areas have been identified that will specifically benefit ~19 major and minor users from all three schools. Among these themes, Vanderbilt has a strong community of investigators focused on advancing our understanding of DNA repair, replication and gene regulation. These researchers will use the microscope to observe how purified multiprotein machines process and maintain the information encoded within DNA through binding, translocation, and remodeling events. A second theme supports Vanderbilt’s robust cytoskeletal and cell mechanics research programs. In this area, the C-Trap is ideal for visualizing and manipulating actin and microtubule filaments, along with their associated proteins and molecular motors. These studies will provide access to a whole new frontier for Vanderbilt investigators who can deeply probe complex associations among cellular machinery. A third theme will investigate the mechanobiology of T-cell receptor-antigen quality and T-cell activation, as well as other receptor- ligand associations and conformational motions. Additional areas of research involve membrane dynamics, biomolecular condensates, forces associated with phase separation and colloids, and studies of AAA+ protein machines that carry out a multitude of cellular processes. The microscope will serve as a regional resource and bolster teaching across all three schools. The C-Trap will be housed in a space where Vanderbilt has purposefully clustered mechanobiology faculty labs and positioned other core resources. Management, support of the microscope and projects, and long-term operation and maintenance of the system will be led by Dr. Matthew Lang, who has over two decades of experience in optical tweezers and single-molecule studies. Collectively, Vanderbilt is ideally positioned to make rapid and significant use of these new capabilities, extending our research scope across a broad range of NIH-sponsored studies.

National Park Service

This announcement is to provide public notice of the National Park Service (NPS), intention to fund the following project with University of Alaska Fairbanks under a Cooperative Ecosystem Studies Unit (CESU) program. CESUs are partnerships that provide research, technical assistance, and education. The project intended modified award is $77,500.00. This is a modification for continuation of an existing agreement, number P10AC00020. STATUTORY AUTHORITY: Agreements Concerning Cooperative Research and Training on NPS Resources (16 U.S.C. 1a-2(j)): The Secretary may enter into agreements with public or private educational institutions, States and their political subdivisions, for the purpose of developing adequate, coordinated, cooperative research and training programs concerning the resources of the National Park System, and pursuant to such agreements, to accept from and make available to the cooperator such technical and support staff, financial assistance for mutually agreed upon research projects, supplies and equipment, facilities, and administrative services relating to cooperative research units as the Secretary deems appropriate. STATEMENT OF JOINT OBJECTIVES/PROJECT MANAGEMENT PLAN: The purpose of this project is to address much needed systematic evaluation and mapping of identified but minimally documented substantial Late Prehistoric age (and earlier) village sites. These sites are located adjacent to lakes within the Brooks Range of northern Alaska and are significant because they contain rare types of features, such as large, stone-ringed communal structures (qargi) and petroglyphs, and exceptionally dense concentrations of house, storage, and hunting-related features. The purpose of this project is to build on existing survey and inventory documentation to systematically document significant Late Prehistoric age (and earlier) village sites located along Brooks Range lakeshores within NOAT and GAAR. These sites are significant because they contain rare types of features that demonstrate a prolonged human presence in an area marked largely by temporary encampments of mobile peoples. Sites targeted in Phase I include Burial, Desperation, Feniak, and Kikitaliorak Lakes located in the northern reaches of Noatak National Preserve. The project will build on existing survey and inventory level documentation to systematically record the lakeside archeological sites and cultural landscapes. This Modification Request is issued to: Three years of field work at the three different sites (XHP-00004, XHP-00017, and MIS-00352) resulted in subsurface testing of 34 features. Data derived from these investigations include stratigraphic descriptions, radiocarbon samples, faunal remains, and lithic, ceramic, and organic artifacts. A total of 12 cubic feet of collections were generated and these include 7 cubic feet of faunal remains and 5 cubic feet of lithic artifacts, organic artifacts, ceramic artifacts, wood samples, and charcoal samples. All of the wood and charcoal from 2010 and 2011 has been identified and the analysis of the 2012 assemblage is currently underway. The wood and charcoal is the only group of collections to be analyzed up to this point. The entire project assemblage contains 655 cataloged specimens including several uncounted faunal and flake lots. This assemblage has been fully processed, cleaned, rehoused, and cataloged according National Park Service curatorial guidelines and is now ready for analysis. Processing and organizing field data is another main component of this project and includes typing field notes, digitizing soil profiles, annotating photographs, and downloading and editing GPS data. Field data processing for 2010 and 2011 is largely finished and we are currently processing data collected during 2012. The partner, in cooperation with the National Park Service will: Complete a basic description of the lithic and faunal assemblages Create maps and other graphics such as artifact plates, site photos, rock art illustrations, and stratigraphic profiles in a publication quality format. Write an introductory context that includes a regional review for Late Prehistoric sites in the central Brooks Range including relevant research questions. Write the main body of the report with a narrative for the work accomplished at each site including: site location and description, stratigraphy and sampling, radiocarbon results, faunal and lithic analysis results, petroglyph descriptions, and overall site interpretations. Assemble text and graphics into a monograph style final report. Make castings of the rubber molded petroglyph from Feniak Lake for NPS visitor center in Kotzebue and UA Museum of the North. NATIONAL PARK SERVICE INVOLVEMENT -Substantial Involvement : The successful completion of this project involves a substantial degree of cooperation between the National Park Service and the proposed principal investigator. The principal investigator for this project will need to conduct initial field assessments with the park archeologist to identify features and review existing mapping and other data compiled in past decades using less sophisticated instruments than are currently available. The UAF archeologist will need to reconcile existing data with input from the park archeologist who was involved in the initial documentation efforts and work together to formulate a research documentation strategy to address data deficiencies and specific resource and park management needs. The NPS will also interface between the cooperator and regional NPS programs that must be tied into the research project: NPS Cultural Landscapes Program and the List of Classified Structures Program. The NPS will provide an archeologist to assist in the 2011 field efforts and will provide housing for the UAF crewmembers while in Kotzebue. The NPS will also conduct any necessary government to government consultations with tribal organizations (e.g., as required for NAGPRA - Inadvertent Discovery of Human Remains Plans of Action for archeological testing). Modifications to research methodologies, testing localities and other areas will be made collaboratively between the NPS and UAF researchers throughout the project as necessary. SINGLE-SOURCE JUSTIFICATION: Department of the Interior Policy (505 DM 2) requires a written justification which explains why competition is not practicable for each single-source award . The National Park Service did not solicit full and open competition for this award based the following criteria: Continuation - The activity to be funded is necessary to the satisfactory completion of, or is a continuation of an activity presently being funded, and for which competition would have a significant adverse effect on the continuity or completion of the activity. Technical contact information: Michael Holt, Michael_holt@nps.gov, 907-442-8316, National Park Service, Alaska Region End of FOA

NHLBI - National Heart Lung and Blood Institute

SUMMARY The annual Vasculata conference has been convening since 2004, and has been hosted by different academic research institutions throughout the United States. Vasculata is co-sponsored by the North American Vascular Biology Organization (NAVBO), which promotes the study of vascular biology and the dissemination of scientific knowledge and discoveries to the next generation of vascular biologists and bioengineers. The NAVBO Educa- tion Committee has selected the University at Buffalo (UB) – SUNY as the host of Vasculata 2026, marking the first time the meeting will be held in Western New York! Vasculata is an intense “boot camp” that provides foun- dational knowledge in vascular biology, as well as the latest discoveries and technologies, to students and post- doctoral trainees. The meeting has grown considerably since the inaugural meeting in 2004 (a group of about 60 people) to now attracting a group of about 100-120 faculty, students, and fellows. UB, especially the Jacobs School of Medicine and Biomedical Sciences (JSMBS), houses a critical mass of faculty with expertise in various areas of vascular biology including, but not limited to, vascular endothelial cell and mural cell biology, inflamma- tory signaling and molecular mechanisms of vascular cell dysfunction in cardiovascular, cerebrovascular, and other organ-specific diseases, metabolic and hemodynamic regulation of vascular function, intercellular commu- nication, angiogenesis, vascular remodeling in development and pathology, stem cell-driven vascular biology, bioengineered vascular grafts, vascular medicine, aneurysms and other blood vessel disorders. UB is within driving distance from other top tier institutions, such as the University of Rochester (collaborating institution in Vasculata 2026), Case Western Reserve University, Cleveland Clinic, Cornell University, Rochester Institute of Technology, Syracuse University, and the University of Pittsburgh (host of Vasculata 2025). Furthermore, UB is home to the a) world-renowned Canon Stroke & Vascular Research Center that focuses on research related to the diagnosis and treatment of vascular disease through minimally invasive image-guided interventions and im- proved imaging modalities, and b) the Gates Vascular Institute that consists of a team of health care specialists from UB’s JSMBS, who provide state-of-the-art vascular, stroke, and cardiac care under one roof. A key strength of our program is the incorporation of bioengineering-based vascular-focused presentations through the involve- ment of faculty from the Departments of Biomedical Engineering at UB (including the Vasculata 2026 Chair) and the University of Rochester. All training and dissemination of new knowledge through lectures, workshops and poster sessions, as well as faculty, student and trainee networking, align with the education mission of the NHLBI.

Vermont Community Foundation — Local Funds

Vermont Community Foundation — Local Funds ($300M in assets) supports nonprofits in VT through grants focused on education, environment, community development, arts. Awards range from $1,000 to $75,000.

Vermont Community Foundation

Vermont Community Foundation ($350M in assets) supports nonprofits in VT through grants focused on education, environment, community development, arts. Awards range from $1,000 to $75,000.

Victoria Foundation

Victoria Foundation provides grants for community-building projects in Greater Victoria and surrounding regions including arts, education, environment, and social services.

Virginia Commission for the Arts

Virginia Commission for the Arts provides grants to support arts and cultural programming, artist fellowships, arts education, and community-based arts projects across VA.

Virginia Commission for the Arts

Virginia Commission for the Arts Arts in Education grants support artist residencies in K-12 schools and community organizations across Virginia, providing sustained arts learning experiences for students and community members.

Virginia Commission for the Arts

The Virginia Commission for the Arts General Operating Support grants provide multi-year funding to established Virginia arts organizations, enabling programmatic stability and sustained delivery of arts and cultural experiences statewide.

NIH

Background: Virtual care, now a mainstay in the Veterans Health Administration (VA), facilitates access to critical clinical and social services for millions of Veterans. The term “virtual care” encompasses a suite of technologies that include VA’s video visit platform, the MyHealtheVet patient portal, mobile apps, remote monitoring devices and tools to collect patient-generated health data. Collectively, these technologies have potential to enhance Veteran care and improve the workflow and workload of VA clinical teams. Yet for many clinical scenarios, evidence regarding the effectiveness, quality, safety and cost implications of virtual care is still in early stages. Understanding factors associated with access to and engagement with virtual care are important for this to be an effective, equitable mode of care delivery within VA. Significance: The Virtual Care Consortium of Research (VC CORE) was established in 2020 to address pressing needs for virtual care evidence within VA. In close partnership with VA’s Office of Connected Care and Digital Health Office, the VC CORE has grown to a diverse network of >380 investigators, clinicians and staff. The VC CORE addresses VA Health Systems Research priority areas for 2026 and is responsive to national legislation pertaining to VA virtual care, including the Cleland-Dole Act of 2022. Foundational VC CORE accomplishments include an extensive portfolio review of VA virtual care projects, an online research and implementation resource library, establishment of a cyberseminar series and monthly newsletter, a State- of-the-Art conference to identify virtual care research priorities and facilitation of > 50 OCC-funded quality improvement and evaluation projects. Innovation and Impact: The VA has been an early innovator in virtual care, with routine use of video visit capabilities, remote patient monitoring platforms, a web-based patient portal, and other technologies for several decades. VC CORE innovations that support virtual care implementation and evaluation include development of a comprehensive database of VA virtual care research, creation of a novel program to support operations-funded virtual care evaluations, and contributions to two Congressionally-mandated reports. Specific Aims: In the proposed VC CORE renewal, we will pursue four Impact Goals (IGs): In IG1, we will strengthen the VC CORE network through targeted growth, enhanced collaboration and partnerships. In IG2, we will foster rapid, rigorous and innovative research and QI activities focused on virtual care. In IG3, we will support VA in its efforts to implement and disseminate virtual care across the enterprise. In IG4, we will generate and synthesize evidence to advance VA practice and policy. Methodology: In IG1, we will grow our network and build more connections between network members and clinical operations partners, support requests for subject matter expertise from Office of Research and Development (ORD) and other VA leaders and support the next generation of investigators through early- career development opportunities. In IG2, we will foster virtual care research by updating VC CORE’s portfolio review, working with existing ORD entities to develop and disseminate data measures relevant to virtual care research and establishing a Veteran Engagement Panel. In IG3, we will identify innovative programs through communication with the VC CORE network and support the dissemination of implementation resources using a SharePoint repository. In IG4, we will track requests from operational and ORD partners (e.g., literature or reporting requests), continue to orchestrate requests for applications for projects funded by OCC and other partners, and synthesize evidence about the value and impact of project findings. Next Steps/Implementation: The VC CORE has emerged as a critical supportive structure that facilitates high- impact virtual care research and evaluation activities within VA. Renewal of the VC CORE will help sustain these achievements and further enhance the impact of virtual care research to support VA as a learning health system.

KNOWINK LLC

Editorial and Design and Graphic and Fine Art Services

VT Arts Council

General operating and project support for arts organizations and individual artists in VT. Funds visual arts, performing arts, literary arts, and arts education.

Waco Foundation

Waco Foundation ($200M in assets) supports nonprofits in TX through grants focused on education, community development, health, arts. Awards range from $2,000 to $75,000.

Warhol Foundation Regional

Project and operating grants for arts organizations and individual artists from Warhol Foundation Regional. Supports visual, performing, literary, and media arts.

Washington Council on the Arts

General operating support grants for arts organizations in Washington. Funded by the National Endowment for the Arts and state appropriations.

Washington Council on the Arts

Project-based grants for arts programming, performances, exhibitions, and community engagement in Washington.

Washington State Arts Commission

Washington State Arts Commission provides grants to support arts and cultural programming, artist fellowships, arts education, and community-based arts projects across WA.

Washington State Arts Commission (ArtsWA)

ArtsWA's Arts in Education program places professional teaching artists in K-12 schools and community organizations throughout Washington State, providing sustained residencies that integrate arts into academic learning.

Washington State Arts Commission (ArtsWA)

ArtsWA's Organizational Support Program (OSP) provides general operating support grants to established Washington arts organizations, enabling long-term planning and programmatic stability across the state.

The Art of Alzheimer's

The Art of Alzheimer's will organize a series of arts-focused activities and workshops to raise awareness and reduce stigmas about people and families living with dementia. The activities will focus specifically on exploring these themes beyond wealthier, less diverse sections of the city. This project serves as a catalyst for more inclusion, hearing more voices, and reaching more people with compelling opportunities to overcome fear, foster empathy, and advance engagement.

WEC Energy Foundation

Supports education, environment, community development, and arts programs through the WEC Energy Group's community foundation.

West Virginia Community Foundation

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

West Virginia Division of Culture and History

The Division of Culture and History provides grants to West Virginia arts organizations and cultural institutions, supporting programming, exhibitions, performances, and heritage preservation that celebrate the state's rich cultural traditions.