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NIDCR - National Institute of Dental and Craniofacial Research

PROJECT SUMMARY/ABSTRACT The calvaria bones of the skull begin to form bone marrow (BM) after birth, and this BM continues to expand with age in both mice and humans. Recent studies show that calvaria BM is not static but dynamically remodels in responses to local and systemic conditions, including pregnancy and disorders of skeletal, hematological, and neurological origin. BM niche formation is thought to be regulated by the intercommunication of skeletal cells (SKCs), vascular endothelial cells (ECs), and hematopoietic cells (HCs), but crosstalk mechanisms between them are complex and largely unknown. BM residing SKCs express platelet-derived growth factor (PDGF) receptors, PDGFR and PDGFRβ. The PDGFRs regulate the proliferation, migration, and differentiation of various mesenchyme-derived cell types in organ development, homeostasis, and tissue repair. Increased receptor signaling has been implicated in diseases such as fibrosis, cardiovascular disease, and cancer. Therefore, PDGF receptor activation and its downstream signaling have been proposed as potential therapeutic targets. Recent work in mice suggests a novel role for platelet-derived growth factor receptor beta (PDGFR) signaling in calvaria BM formation. Mice with a gain-of-function (GOF) mutation in PDGFR exhibit dramatically increased calvaria bone and BM size by 2-3 weeks of age, compared to wild type mice that do not generate significant calvaria BM until full adulthood. This precocious BM growth is accompanied by an expanded vascular network. Because PDGFR is expressed in SKCs but not in ECs or HCs, these results point to SKCs as the cellular origin of signals that increase calvaria vasculature and BM. The central hypothesis is that skeletal PDGFR promotes BM formation through an angiogenesis-directed mechanism. This project will address the central hypothesis with the following aims: 1) Characterize how PDGFR GOF causes dramatic expansion of calvaria vasculature and BM in juvenile mice, and 2) Determine the extent to which angiogenesis mediates BM formation in wild type and PDGFR mutants. In Aim 1, a skeletal-specific Cre recombinase mouse line will be used to conditionally induce a GOF Pdgfrb knock-in allele. The developmental processes of BM niche formation in wild type and PDGFRβ mutants will be defined using multiphoton light sheet imaging at 3 dimensions and transcriptomics. In Aim 2, experiments will focus on evaluating the contribution of ECs to BM formation with pharmacological angiogenic inhibition. The importance of skeletal and vascular coordination is evident from a close relationship between skeletal disorders, vascular malformation, and hematopoietic defects. The results of this project will generate a new mouse model to investigate calvaria bone/BM regeneration in future R01s and provide novel insights into the cell-cell interaction mechanisms that rebuild calvaria bone and BM.

City of Pendleton

Pendleton Water System Improvements

Pennsylvania Infrastructure Investment Authority (PENNVEST)

PENNVEST provides grants and low-interest loans for drinking water, wastewater, and stormwater infrastructure projects in Pennsylvania, including system upgrades, capacity improvements, and new construction.

NIAID - National Institute of Allergy and Infectious Diseases

Summary Central Nervous system (CNS) perivascular macrophages are part of a group of macrophages names border- associated macrophages (BAM). Most BAM are generated during embryogenesis and maintained by self- division. We developed a genetic system in which the main type of BAM (CD206H) is ablated in the brain. When experimental autoimmune encephalomyelitis (EAE) is induced in these BAM-ablated mice, the disease is much more severe, indicating that healthy BAM are generally protective from neuroinflammatory diseases such as EAE. Given that in the CNS perivascular BAM are located in the perivascular space formed between the endothelium and the astrocyte feet that delimit the blood-brain barrier (BBB), we hypothesize that this unique location endows BAM with the capacity to reinforce the BBB thereby limiting the flow of inflammatory cells into the CNS. In contrast to BAM, monocyte-derived macrophages are not resident of the CNS but swiftly enter into the CNS in diseases such as EAE and multiple sclerosis (MS), together with a large number of other inflammatory myeloid and lymphoid cells. In contrast to what we hypothesize is the function of BAM, monocyte-derived macrophages are known to be part of the pathogenesis of EAE and MS, being considered the main executioners of demyelination through phagocytosis of pieces of myelin. In this R21 application, we propose to test the hypothesis that healthy perivascular BAM contribute to the barrier function of the BBB. We will also determine whether BAM, a subgroup of which express MHC class II, can affect the activation profile of T cells. We propose two specific aims. In Aim 1, we will induce EAE in mice that lack BAM and mice with normal BAM and will monitor daily the inflow of inflammatory cells (myeloid and lymphoid) into the spinal cord of mice. We will inject monocytes labeled at the Ccr2 locus to follow the fate of monocyte-derived CCR2+ macrophages inside the inflamed CNS, and monitor the permeability of the BBB under unstimulated conditions or EAE in mice. In Aim 2, we will focus on the differences that BAM presence or absence would make on the T cell activation state and cytokines produced, We will also bypass the priming in lymph nodes by using the adoptive transfer model of activated T cells and monitor the fate of these T cells in mice with normal BAM versus ablated BAM. Finally, in collaboration with Dr Gabriel Victora, we will use a novel mouse strain, named uLipstic, to label T cells and identify what are the CNS cells that first interact with myelin-reactive T cells. At the end of the proposed studies, we will deliver a clear picture of whether perivascular CNS-resident BAM are an important player in EAE, thus suggesting that reinforcing the BAM compartment could have a beneficial impact in neuroinflammatory diseases.

NIA - National Institute on Aging

PROJECT SUMMARY/ABSTRACT Cognitive decline, particularly memory impairment, poses an increasing challenge in aging populations, leading to reduced quality of life and escalating healthcare costs, especially in Alzheimer's Disease and Related Dementias (ADRD). While transcranial alternating current stimulation (tACS) has emerged as a promising non- invasive approach for memory enhancement, its effectiveness is limited by a lack of precision in stimulation protocols. The primary goal of this study is to optimize high-resolution tACS intervention parameters and develop a personalized, connectivity-guided closed-loop system to improve memory performance in aging adults. This application is supported by compelling pilot data demonstrating the feasibility of personalized and adaptive tACS for memory enhancement, providing a strong foundation for the proposed study. Aim 1 will investigate the impact of personalized tACS applications within a day (patterned vs. continuous) and across multiple days (one-time vs. repeated consecutive dosing) on the durability of memory enhancement. We will compare six tACS protocols, including continuous and patterned stimulation, over one, three, or five consecutive days. This aim will also establish dose-response functions to identify the optimal stimulation frequency and application pattern that maximize memory enhancement over time. Memory and executive control abilities—such as working memory capacity, filtering efficiency, interference suppression, and long-term memory recognition—will be examined before, immediately after, and at one-week and one-month follow-ups. These cognitive metrics will be complemented by multimodal imaging (EEG, f/MRI) to investigate the neurobiological mechanisms underlying memory improvements, focusing on theta-gamma phase-amplitude coupling and theta phase synchronization, and to identify potential biomarkers of nonresponse. Aim 2 will develop a connectivity-guided closed-loop tACS system that adjusts stimulation parameters on-the-fly based on neural synchronization and memory performance. This system will track low-frequency oscillatory synchronization, an aspect of brain connectivity, in the frontotemporal cortex, periodically adjusting stimulation to optimize memory performance. We hypothesize that adaptive modulation will yield more efficient memory enhancement than static protocols, emphasizing the importance of accounting for fluctuations in functional brain state. This research aims to advance precision aging by identifying optimal tACS protocols and developing an adaptive system that tailors stimulation to individual neural connectivity patterns. The findings will provide novel causal insights into the neurobiological mechanisms of memory, with potential to inform interventions for ADRD. This work holds promise for improving cognitive function in aging adults and offers a non-pharmacological alternative or adjunct to current therapeutic options for age-related cognitive decline, with direct relevance to ADRD intervention development.

State of New York

6340 ? Comprehensive PROS with Clinic Personalized Recovery Oriented Services (PROS) is a comprehensive recovery oriented program for individuals with severe and persistent mental illness. The goal of the program is to integrate treatment, support and rehabilitation in a manner that facilitates the individual's recovery. Goals for individuals in the program are to: improve functioning, reduce inpatient utilization, reduce emergency services, reduce contact with the criminal justice system, increase employment, attain higher levels of education and secure preferred housing. There are four "service components" in the program: Community Rehabilitation and Support, Intensive Rehabilitation, Ongoing Rehabilitation and Support and Clinical Treatment. Units of Service: Report the sum of the total monthly units of service for the year. 7340 ? Comprehensive PROS without Clinic PROS is a comprehensive recovery oriented program for individuals with severe and persistent mental illness. The goal of the program is to integrate treatment, support and rehabilitation in a manner that facilitates the individual's recovery. Goals for individuals in the program are to: improve functioning, reduce inpatient utilization, reduce emergency services, reduce contact with the criminal justice system, increase employment, attain higher levels of education and secure preferred housing. There are four "service components" in the program: Community Rehabilitation and Support, Intensive Rehabilitation, Ongoing Rehabilitation and Support and Clinical Treatment. This program does not include the optional Clinic Treatment component. Units of Service: Report the sum of the total monthly units of service for the year.

NYS Office of Mental Health

6340 ? Comprehensive PROS with Clinic Personalized Recovery Oriented Services (PROS) is a comprehensive recovery oriented program for individuals with severe and persistent mental illness. The goal of the program is to integrate treatment, support and rehabilitation in a manner that facilitates the individual's recovery. Goals for individuals in the program are to: improve functioning, reduce inpatient utilization, reduce emergency services, reduce contact with the criminal justice system, increase employment, attain higher levels of education and secure preferred housing. There are four "service components" in the program: Community Rehabilitation and Support, Intensive Rehabilitation, Ongoing Rehabilitation and Support and Clinical Treatment. Units of Service: Report the sum of the total monthly units of service for the year 7340 ? Comprehensive PROS without Clinic PROS is a comprehensive recovery oriented program for individuals with severe and persistent mental illness. The goal of the program is to integrate treatment, support and rehabilitation in a manner that facilitates the individual's recovery. Goals for individuals in the program are to: improve functioning, reduce inpatient utilization, reduce emergency services, reduce contact with the criminal justice system, increase employment, attain higher levels of education and secure preferred housing. There are four "service components" in the program: Community Rehabilitation and Support, Intensive Rehabilitation, Ongoing Rehabilitation and Support and Clinical Treatment. This program does not include the optional Clinic Treatment component. Units of Service: Report the sum of the total monthly units of service for the year

NIA - National Institute on Aging

Project Summary/Abstract Fibrillar alpha-synuclein (αSyn) aggregates accumulate in dementia with Lewy bodies (DLB), Parkinson’s disease (PD), and multiple systems atrophy (MSA), with distinct topological spread in association with the progression of each disease. While DLB and PD fibrils are structurally similar, MSA fibrils are distinct. PET molecular imaging of amyloid plaques and tau tangles has revolutionized diagnosis, understanding, and clinical trials in Alzheimer’s disease (AD), and PET imaging of αSyn pathologic changes in life has similar potential for these αSyn-associated ADRD that can arise in isolation as well as in association with AD co-pathology. We previously identified SY08 as a molecule that selectively binds αSyn fibrils outside of the ThioT binding site and does not bind αSyn monomer, amyloid-42, or tau fibrils. SY08 binds Lewy body disease brain tissue homogenates with high affinity and with high selectivity over AD tissue, with no significant off target binding to more than 50 CNS targets. Brain [11C]SY08 retention was increased in rodent PD αSyn models. In non-human primates, [11C]SY08 PET imaging showed rapid CNS entry across brain regions; plasma radioactivity analysis showed rapid clearance from blood with limited brain uptake of radiometabolites. In the first-in-human [11C]SY08 PET study (NCT06098612), we detected increased brainstem and cortical binding in PD and DLB, yet limited binding in MSA participants, compared to aged-matched healthy control (HC) participants. Building on these results, the overall goals of this proposal are to 1) evaluate whether fibrillar αSyn burden measured with [11C]SY08 differentiates DLB, PD, and MSA from each other and from HC and AD, and 2) to relate regional [11C]SY08 binding to the expected topology of αSyn pathologic changes and clinical features. As an exploratory aim, we will evaluate if [11C]SY08 binding is increased in isolated REM sleep behavioral disorder (iRBD), a prodromal synucleinopathy state. We hypothesize that [11C]SY08 PET imaging will distinguish DLB, PD, and MSA from HC and from AD participants; that binding in DLB and PD will be higher than in MSA; and that the pattern of [11C]SY08 retention will reflect the distinct topographies of αSyn pathology and the clinical features of each synucleinopathy, without impact of co-morbid amyloid- when present. We also hypothesize that brainstem [11C]SY08 retention will be elevated in iRBD. To accomplish these objectives, we will acquire neurologic exams, detailed cognitive testing, simultaneous [11C]SY08 PET-MRI, and biomarkers of brain amyloid deposition in PD, DLB, and MSA participants with evidence of αSyn pathology on skin biopsy, AD, HC, and participants with isolated RBD. Together, these efforts will establish the potential for developing [11C]SY08 PET as an imaging marker of αSyn pathology in PD, DLB, MSA, and iRBD.

Metropolitan Opera Association, Inc.

Replace the roofing system over the 8th Floor Stafe Roof, and 7th Floor North and 7th Floor South Roofs (Siplast Roof-torched applied modified bitumen roofing system, including fully adjered insulation and cover board. Third floor South roof will be repla

Montgomery

Phase II � IT/Communications/Records & Content Management Systems

NCI - National Cancer Institute

PROJECT SUMMARY Funds are requested to provide partial support for the inaugural FASEB Science Research Conference (SRC) on biomolecular condensates, titled "Phase Transitions in Cellular Signaling and Disease”, to be held from January 11–15, 2026, in Melbourne, Florida, USA. Biomolecular condensation has been recently discovered to be a ubiquitous phenomenon in living systems, supporting normal physiology and driving disease processes, including cancers and neurological disorders. These discoveries have generated immense interest among biologists, chemists, physicists, engineers, and computer scientists to develop an integrated experimental, theoretical, and computational framework to understand phase transition as a mechanism for programming cellular signaling, stress regulation, and genome organization. Aberrant behaviors of condensates have been shown to result in alterations in soluble protein homeostasis, dysregulation of signaling events in the cytoplasm, and activation of oncogenic transcriptional programs in the nucleus. These discoveries have also fueled new directions in drug discovery research, which are currently pursued by biotech and pharma companies. The 2026 conference on biomolecular condensates will feature two keynote lectures, 30 invited speakers and session chairs, including rising stars, and up to 150 attendees. The specific objectives of the conference are to stimulate and enable: 1) scientific knowledge exchange, both among academic researchers and between academia and industry, 2) professional networking and collaboration, and 3) peer mentoring and support for early-career scientists. Besides keynotes, invited and contributed talks, and poster sessions, the program will include a Career Development Workshop for trainees and junior faculty members to address career choices and milestones in a panel discussion format. It will also feature a Meet-the-Expert/Speaker Session covering a range of professional development topics, fostering an interactive platform for knowledge sharing, peer mentoring, and professional networking. Through these activities, this FASEB conference will catalyze new connections between molecular biophysics, cell and molecular biology, cancer biology, neuroscience, and drug discovery communities, enabling exchanges of cutting-edge discoveries and identification of major challenges as the field moves forward.

Ansonia

Phone/Data/Camera System Upgrade

NINDS - National Institute of Neurological Disorders and Stroke

Human induced pluripotent stem cell (hiPSC) differentiation offers a unique perspective on species- specific aspects of neuronal development. We employed high-temporal resolution single-cell expression analysis to investigate the mechanisms underlying prolonged and enhanced neurogenesis in the human spinal cord compared to mice. Canonical correlation analysis revealed "human-specific" progenitor clusters marked by early co-expression of NKX2-2 and OLIG2. Lineage tracing revealed that these cells are bone fide motor neuron progenitors. Unlike classical motor neuron progenitors (pMNs), these more ventral motor neuron progenitors (vpMNs) exhibit increased NOTCH and WNT activity, generating motor neurons in a delayed and protracted manner. Furthermore, vpMNs undergo more rounds of cell division, yielding approximately five times more motor neurons that are enriched in motor neuron subtype innervating limbs. Evolution of a new progenitor domain is a novel mechanism through which human CNS increases its size and complexity, distinct from transit amplifying progenitors described in the developing human neocortex. Our proposed research aims to answer four outstanding questions: 1) Is NKX2-2 expression both necessary and sufficient to activate the vpMN program, leading to extended motor neuron genesis? 2) What evolutionary changes in the OLIG2 regulatory system allow human-specific co-expression of OLIG2 and NKX2-2? 3) Does increased NOTCH signaling observed in vpMNs contribute to their specification and delayed neurogenesis? 4) Do vpMNs and pMNs generate different subtypes of motor neurons during human neurogenesis? Addressing these questions will provide valuable insights into the molecular and cellular mechanisms that contribute to the increased number and complexity of motor neurons produced during the human spinal cord development. These insights might lead to improved motor neuron disease models that recapitulate more faithfully human pathology.

NIEHS - National Institute of Environmental Health Sciences

Project Summary The majority of Parkinson’s disease (PD) cases are not caused by an inherited monogenic mutation, and disease etiology involves a combination of genetic and environmental factors. Epidemiological studies show that pesticide exposure, particularly to organochlorine pesticides such as dieldrin, increases the risk of sporadic PD. In a model of increased PD susceptibility, mice exposed to dieldrin during development show male-specific increased susceptibility to adult exposure to the dopaminergic toxicant MPTP and, in data from our previously NIEHS-funded work, α-synuclein (α-syn) preformed fibrils (PFFs). Results in this two-hit model demonstrate that developmental exposure to dieldrin leads to largely sex-specific changes in epigenetic modifications from birth to 9 months of age within pathways related to critical steps in early neurodevelopment, dopaminergic neuron differentiation, synaptogenesis, synaptic plasticity, and glial-neuron interactions, suggesting that developmental dieldrin exposure disrupts critical neurodevelopmental pathways, thereby impacting risk of late-life diseases, including PD. However, the early neurodevelopmental effects of this exposure remain incompletely understood. In addition, while these effects are thought to be mediated by direct impacts of dieldrin on the developing brain as dieldrin crosses the placenta and can be detected in the neonatal brain, disruption of placental serotonin (5HT) has emerged as a potential indirect mechanism of developmental neurotoxicity (DNT). Because the placenta is the primary source of 5HT for the developing fetal brain and proper regulation of placental serotonin is essential for proper fetal neurodevelopment, disruption of placental 5HT can cause behavioral and neurological changes throughout the lifespan. Such disruption by genetic, pharmacologic, or toxicologic mechanisms increases the risk of neurodevelopmental disorders, but long-term outcomes on late-life diseases are largely unexplored. This grant aims to test two related yet independent hypotheses. In Aim 1, we hypothesize that dieldrin, known to disrupt monoaminergic systems in the adult brain, may also affect these systems within the placenta; this disruption of placental 5HT may be an additional indirect mechanism of DNT. In Aim 2, we hypothesize that developmental dieldrin exposure alters the development of fetal and neonatal monoamine systems.

Louisa Boren STEM PTA

The Louisa Boren School Community is embarking on a project to make the playground more family friendly for use by the neighborhood. The project includes the installation of a bench to serve as a resting place, a site clean up and adding paint to 4 square courts and the area adjacent to the new bench. A community celebration at the playground, 5950 Delridge Way South West, is planned for June.

Asphalt Green, Inc.

Replace (20 existing pool filtration system at the AquaCenter. These filters provide clean water to both Warm water Therapy Pool and Olympic Pool which serves in excess of 1,400 people daily.

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary/ Abstract The mosquito species Aedes aegypti is the primary global vector of important human pathogens, including dengue and yellow fever viruses. The attributes that make Ae. aegypti an efficient vector of these pathogens – such as small flight ranges and the proclivity for human blood feeding – also impact the genetic structure of populations at local and regional scales. Aedes aegypti has recently re-emerged as a medically important insect in the (semi)arid American southwest (ASW, California, Arizona, New Mexico, Nevada, and western Texas), and populations are rapidly dispersing along a northward gradient. This proposal aims to investigate the structural properties of localized and regional Ae. aegypti population networks in this unique landscape to identify weaknesses and breakpoints in (sub)population connectivity which can inform mosquito control interventions. Our central hypothesis is that Ae. aegypti population dynamics in the ASW are best explained by a core-satellite metapopulation framework in which large urban centers maintain genetically diverse and stable populations (i.e., cores) while connectivity (i.e., gene flow) and invasion of satellites outside of cores is best explained by distance to a source, size of urbanized sites, and density of human populations. To investigate population structure across the ASW, we will systematically sample individuals from urban centers of varying human population densities, genotype individuals using a single-nucleotide polymorphism array (SNP-chip), and then use a combination of landscape genetic approaches and network analyses to quantify population connectivity and determine the influence of commerce (i.e., roads) systems on the structure of ASW Ae. aegypti populations. To investigate population structure within ASW cities, we will first intensely and systematically sample individuals from multiple locations and time points within four urban cores with historical, established, and recently invaded Ae. aegypti populations. We will then genotype individuals using whole genome sequencing and will analyze networks using persistent homology approaches to determine the extent to which population structure at local scales is driven by founder effects (e.g., time since invasion), physical barriers to random mating (e.g., site fidelity), and individual limits of dispersal (e.g., kinship networks). Our results will provide a novel and innovative assessment of Ae. aegypti population biology and invasion dynamics at multiple spatial scales, which can better guide mosquito control intervention efforts in the region.

NSF

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2025. The fellowship supports research and training of the fellow that will contribute to biology in innovative ways. Effective information processing is crucial for species to respond appropriately to their environment, particularly in social species like humans that integrate a wide range of individual experiences into collective responses. Theoretical models that are grounded in real world observations are needed to explain and predict patterns of social communication across species. This research addresses this need by using the common eastern bumblebee (Bombus impatiens) to trace the flow of nutritional information throughout the colony. Bumblebee colonies are an optimal model to test key hypotheses in social communication due to their complex social behaviors and ease with which they can be manipulated for study. This research will leverage this model, integrating methods in behavioral ecology and deep-learning, to study the role of colony size, communication, and individual variability on the social network formed following a successful foraging expedition. This research will be accompanied by educational activities focused on increasing STEM engagement among incarcerated college students, who historically have not had opportunities to critically engage with scientific thinking. This research seeks to answer three questions: 1) What are the individual dynamics which underlie bumblebee communication? 2) How does the communication network change with colony size? 3) How does individual variation impact communication? To answer these questions, the fellow will utilize a deep-learning pipeline to track the location of all bees in a colony, as well as their body parts. The fellow will generate a multimodal social network consisting of different modalities of interaction between bumblebees. An experiment will be designed to monitor network behavior before and after introducing a highly nutritious foraging source discovered by a single bee. This will identify key “network archetypes” in bumblebee communication and examine how these archetypes vary between individuals. Through answering these questions, this research will develop an empirically rooted framework of information processing within a social setting. The fellow will receive training in analysis of real-time foraging dynamics, naturalistic rearing settings, and mathematical modeling of biological networks. In the spirit of open science, findings will be incorporated into outreach events with the UW-Madison Agriculture Institute, and all data and computational methodologies will be broadly disseminated. The fellow, in collaboration with the UW-Madison Prison Education Initiative, will also develop biology curricula and courses to teach incarcerated students across Wisconsin. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2025. The fellowship supports research and training of the fellow that will contribute to biology in innovative ways. A fundamental goal of evolutionary biology is to understand how organisms adapt and change in response to their environments. But this is challenging to study in nature because most organisms we observe today have been evolving gradually in concert with their environmental conditions for thousands to millions of years. To work around this challenge the fellow will use the wild population of parrots (genus Amazona) in southern California, which descend from pet birds released within the last 70 years, as a natural experiment. This natural experiment will reveal how quickly bird populations are able to adapt to new environments and reveal the physical and genetic changes that help them to survive and thrive alongside humans in urban areas. Members of the local southern California community can play an active role in the project by contributing their photos and observations of parrots to community science databases. Additionally, the fellow will work with education specialists from the Natural History Museum of Los Angeles County to develop public presentations and table displays informing visitors about ongoing study of the well-known southern California parrots. Because urbanization and human development continue to modify environments at a global scale, we need to understand the capacity of organisms to adapt to these increasingly urbanized landscapes. This project will treat the independent introduction and establishment of four species of Amazona parrots from the pet trade into southern California as a replicated experimental framework for studying the ability of birds to rapidly adapt to a highly urbanized environment. Undergraduate and graduate researchers will be trained in using museum specimens to quantify the physical and genetic characteristics of each species. These characteristics will be quantified in each species’ native range and then compared to the wild parrot populations across urban southern California. After quantifying the extent of phenotypic, behavioral, and genomic adaptation in each species, the fellow will search for changes shared across species with parallel direction and similar magnitude. Any parallel changes identified may reveal broadly shared responses that shape the evolutionary trajectories of vertebrate species facing increased urbanization across the globe. Ultimately, this project will increase our understanding of the speed and repeatability of adaptation to urbanization in wild vertebrate populations. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NIAID - National Institute of Allergy and Infectious Diseases

Immune responses can be evoked through diverse inducible pathways and several genes in these pathways are under investigation as putative therapeutic targets, yet it is likely that additional regulators of immune responses are present and remain undescribed. Recent data has shown potassium (K+) efflux through ATP-gated inward rectifier potassium (KATP) channels reduces virus replication and virus-mediated mortality in mammals, fruit flies, honey bees, and mosquitoes. These data raise the intriguing question of how ion channels and K+ efflux can regulate the antiviral immune response, which are two seemingly disconnected physiological systems, and is the focus of this proposal. KATP channels act as molecular sensors of the cell by coupling cell metabolism to the electrical activity of the cell via the cell membrane potential. Thus, the premise of this proposal is that KATP channels are functionally coupled to antiviral immunity by K+ efflux controlling neurosecretion, bioavailability of ATP, and kinase activity that are essential for circulatory homeostasis, function of the RNAi machinery, and reactive oxygen species generation, respectively. We will directly test the hypothesis that KATP channels are essential to antiviral immune responses in the vector by regulating 1) circulatory homeostasis 2) antiviral RNAi machinery, and 3) products of aerobic respiration that regulates antiviral immune pathways. The experiments outlined in this proposal will systematically test this hypothesis and delineate the involvement of each physiological system to KATP-mediated viral immunity in model organisms that will yield insights to regulation of antiviral immune responses in humans. In Specific Aim 1, we will test the influence of viral infection and modulation of K+ efflux through KATP channels to dorsal vessel contraction dynamics and circulatory homeostasis through gene silencing and transgenic approaches. The data collected in SA1 will bolster our understanding of physiological systems driving virus infection in a competent vector. In Specific Aim 2, we will expand our preliminary results that clearly indicate KATP channels interact with the antiviral RNAi pathway, but do not define the point of interaction. We will perform small RNA sequencing from transgenic mosquitoes to determine whether the defect is in dicer complex or in downstream steps, such as assembly of RISC complexes. The data collected in SA2 will address the mechanism of how ion channels can alter function of antiviral RNAi machinery, which is currently unresolved. In Specific Aim 3, we will test if reduced DENV-2 replication after KATP channel activation is due to ROS/antioxidant-mediated regulation of antiviral immune pathways. The data collected in SA3 will yield mechanistic insights regarding the functional linkage between KATP channels and antiviral RNAi pathways that can be used to inform downstream therapeutic development. Combined, the data generated in this study will fill fundamental gaps in our knowledge of how antiviral immune responses are triggered and will identify putative intervention points to interrupt viral replication.

Christiana Care Health System

Non-Profit

Prime Electric Co., Inc.

Electrical Systems and Lighting and Components and Accessories and Supplies

Defense Department

In accordance with the Privacy Act of 1974, the Department of the Army is modifying and reissuing a current system of records notice (SORN) titled "Personnel Security Clearance Information Files," A0380-67 DAMI. The SORN is being retitled "U.S. Army Security and Foreign Disclosure Files," with a new identifier of A0 0001 DAMI. Originally established to facilitate the processing of personnel security clearance actions, the SORN also documented clearances granted or denied and confirmed eligibility for access to classified information or assignment to sensitive positions. A separate notice rescinding Army SORN A0001 DAMI, "Controlled Accountable Document Inventory System," is being published elsewhere in this issue of the Federal Register. This update incorporates the DoD standard routine uses and supports additional information sharing outside of the DoD. It also expands the authorities for maintaining the system, integrates records previously managed under the Controlled Accountable Document Inventory System, addresses records maintained across all general intelligence security disciplines, and expands on the purposes of such uses. Additionally, the update revises system locations and managers. These changes align the SORN with modernized automation systems and ensure compliance with applicable regulatory requirements.

NIDCR - National Institute of Dental and Craniofacial Research

The R00 phase will establish an independent laboratory to complete the planned studies on how Selenomonas sputigena (Ss), a motile oral bacterium strongly associated with early childhood caries (ECC), colonizes tooth surfaces and organizes with Streptococcus mutans (Sm) to promote virulent, spatially structured biofilms. ECC remains a major public health problem driven by biofilm formation under sugar-rich conditions, leading to rampant tooth decay and systemic complications in children. The long-term objective is to identify motility-driven mechanisms of supragingival biofilm virulence that can be targeted to reduce ECC burden. The central hypothesis is that Ss motility modulates early surface colonization and mixedspecies structuring with Sm, generating localized acidogenic niches that exacerbate enamel demineralization. To test this hypothesis, the project will 1) characterize Ss motility in relation to surface colonization and biofilm initiation under conditions relevant to the oral environment; 2) determine the spatiotemporal assembly of S~Sm biofilms and site-specific gene expression using single-cell and in situ transcriptomics integrated with local pH mapping and enamel demineralization readouts; and 3) investigate Ss-mediated colonization, interspecies spatial structuring/omics and biofilm virulence in vivo while assessing strategies that disrupt motility-modulated assembly. High-speed live imaging with quantitative trajectory analysis will define motility and colonization behaviors, while single-cell and spatial transcriptomics will resolve localized transcriptional states and an established rodent caries model will connect spatial organization to disease severity. The expected outcome is a mechanistic framework linking motility to cariogenic function and actionable targets for prevention. In addition, it will provide a platform to study other motile oral bacteria in health and disease, which remain understudied, and position the laboratory for sustained, independent investigation and future R01-level studies.