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NIAID - National Institute of Allergy and Infectious Diseases

Kingella kingae is an invasive gram-negative pathogen that is a leading cause of bone and joint infections in young children, accounting for up to 88% of osteoarticular cases in children <4 years old. In addition, K. kingae is an important cause of invasive bloodstream infections in young children. Complications of osteoarticular infections in children include abnormal bone growth, decreased joint mobility, unstable joint articulation, and chronic joint dislocation, with residual skeletal dysfunction in 10-25% of cases. Complications of invasive bloodstream infections include multi-organ injury and mortality. Roughly 25% of K. kingae isolates possess β-lactamase activity, and many of these isolates are resistant to other antibiotics as well, raising concern about approaches to treatment in the future and underscoring the need for novel therapeutics. The pathogenesis of K. kingae disease begins with colonization of the oropharynx, followed by invasion of the bloodstream and spread to bones, joints, and other sites. We have established that K. kingae produces type IV pili (T4P), which play a critical role in adherence to epithelial cells and extracellular matrix proteins and augment the RtxA toxin in promoting efficient translocation across polarized epithelial monolayers, important steps in colonization and invasion of the bloodstream. We have discovered that K. kingae T4P pili contain pilus-associated adhesins called PilC1 and PilC2, which promote pilus biogenesis and mediate adherence and twitching motility. PilC1 and PilC2 share some structural homology but have little amino acid homology and possess different binding and twitching motility properties. Based on mass spectrometry analysis of purified T4P, homology analysis, and structural modeling, we have found that K. kingae T4P also contain multiple minor pilins, including the FimT, PilV, PilW, PilX, and PilE minor pilins encoded by the fimTpilVWXE locus. Bacterial 2-hybrid results and AlphaFold3 predictions suggest that PilC1 and PilC2 form a heterodimer and interact with a minor pilin complex. In this proposal, deploying high- resolution electron and fluorescent microscopy, biochemical techniques, and molecular and cell biological methods, we will elucidate the physical relationship of PilC1 and PilC2 with each other, characterize the physical relationship of PilC1-PilC2 and with the pilus fiber, and define the roles of PilC1 and PilC2 in K. kingae trafficking across polarized respiratory epithelial cells. The proposed studies will provide insights into the design of novel therapeutics against K. kingae and potentially other pathogens that produce T4P and may also shed light on other closely related systems such as the type II secretion system in gram-negative bacteria, the competence system for DNA uptake in gram-positive bacteria, and flagella in archaea.

NIDCR - National Institute of Dental and Craniofacial Research

PROJECT SUMMARY Sjögren’s disease (SjD) is a chronic autoimmune disease characterized by immune cell infiltration of the exocrine glands, which mainly comprise the salivary glands (SGs) and lacrimal glands (LGs). An accumulating number of studies show a significant association between the prevalence of autoimmune diseases and abnormal lipid metabolic conditions and wherein changes in lipid metabolism contribute to disease development. However, how abnormal lipid/cholesterol metabolic conditions contribute to SjD development is unclear. Currently, most patients are diagnosed at later stages of the disease. Therefore, understanding the earlier events in disease development prior to clinical manifestations is essential to identify novel targets for therapeutics and new diagnostic tools for early detection of SjD in at-risk populations, such as those with changes in lipid/cholesterol metabolism. Our preliminary studies found that the expression of INSIG1 and INSIG2, negative regulators of cholesterol synthesis, was significantly downregulated in SjD patients, thus resulting in high cholesterol levels. In agreement with these findings, we found that mice with a deficiency for Insig1/2 in the SGs (Insig1/2 cKO mice) exhibited SjD-like phenotypes with complete penetrance. Interestingly, our preliminary study shows that defects in exocytosis, a system for salivary protein secretion, and elevation of oxidative stress are detectable prior to SjD-like phenotypes (acinar cell death/hyposalivation and autoantibodies detection/inflammation) appear in Insig1/2 cKO mice. Therefore, this study aims to determine how cholesterol metabolic abnormalities in the SGs lead to exocytosis dysregulation and acinar cell death (Aim 1), and how cholesterol metabolic aberrations induce oxidative stress-inflammation (Aim 2) in SjD. In Aim 1, we will track exocytosis under a live-imaging system using newly developed Gate16-eGFP reporter mice, allowing us to visualize the dysregulated exocytosis process in Insig1/2 cKO mice. In addition, we will identify the underlying mechanism that leads to dysregulated exocytosis by genomics and proteomics approaches. In Aim 2, we will determine how oxidated cholesterol (a.k.a. oxycholesterol), a harmful cholesterol linked to inflammation, is induced and contributes to SjD pathogenesis and characterize the immune response to defects in local tissue homeostasis. A detailed understanding of the mechanism(s) by which cholesterol metabolism links to exocytosis and inflammation and how these cascades and loops contribute to SjD will provide new knowledge of the pathogenesis of SjD, advancing our understanding of autoimmune diseases.

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary Tuberculosis (TB) remains a leading cause of mortality worldwide, with lung damage being a key driver of disease severity and poor outcomes. Alveolar epithelial cells are critical for maintaining lung homeostasis and promoting repair, processes that are tightly regulated by Wnt/β-catenin signaling. Our preliminary data indicate that Mycobacterium tuberculosis (Mtb)-induced inflammation disrupts alveolar epithelial integrity in TB-susceptible mice, leading to impaired surfactant production and defective lung regeneration. Strikingly, this is associated with a significant reduction in β-catenin levels. Notably, inhibition of type I interferon (IFN-I) signaling restores β-catenin expression, suggesting a previously unrecognized role of IFN-I in suppressing Wnt/β-catenin activity and alveolar repair. We aim to investigate how chronic IFN-I signaling impairs Wnt/β-catenin function, leading to defective epithelial repair and exacerbated lung pathology in TB. Specifically, in aim1, we will define the role of Wnt/β-catenin in alveolar epithelial repair following Mtb infection. We will assess how Wnt/β-catenin activation or inhibition influences alveolar type 2 (AT2) cell proliferation, differentiation, and stemness using murine and human primary alveolar cells. Additionally, we will evaluate lung histopathology, epithelial marker expression, and AT2 cell differentiation in TB-resistant and susceptible mice. In aim2, we will determine how IFN-I signaling suppresses Wnt/β-catenin activity during TB-induced lung damage. Using genetic and pharmacological approaches, we will investigate the molecular mechanisms by which IFN-I signaling modulates Wnt/β-catenin function and identify key mediators of IFN-I–Wnt/β-catenin crosstalk as potential therapeutic targets. Finally, in the aim3 we will evaluate the therapeutic potential of targeting Wnt/β-catenin and IFN-I pathways to enhance alveolar repair. We will test Wnt/β-catenin activators, such as GSK3β and Porcupine inhibitors, as well as IFN-I blockade using anti-IFNAR antibodies in murine TB models. Therapeutic efficacy will be assessed through histopathological analysis, epithelial barrier integrity, inflammatory responses, and bacterial burden. This study will provide novel insights into the interplay between IFN-I signaling and Wnt/β-catenin in TB pathogenesis, uncovering mechanisms that impair alveolar repair. By identifying host-directed therapeutic strategies, we aim to enhance lung recovery and improve outcomes for TB patients.

NIA - National Institute on Aging

PROJECT SUMMARY Immigrant workers are integral to American society, contributing to its cultural intactness and economic growth. While much attention has been given to understanding and addressing the health needs of these workers, the equally important challenge of caring for their aging parents has been comparatively overlooked. These aging parents, referred to in this proposal as the “zeroth generation” immigrants, represent a unique demographic whose lives in the US are deeply intertwined with those of their adult children—the first generation. The zeroth generation faces profound challenges, including cultural adjustments, language barriers, social isolation, loss of independent access to resources, and the absence of familiar support systems. These challenges are especially pronounced among zeroth-generation older Chinese immigrants, making their experience even more difficult than that of their adult children. Emerging research underscores the critical role of sleep and circadian function in healthy aging. Studies suggest that immigrant workers are susceptible to sleep disorders and circadian disruptions, likely due to heightened migration stress and acculturation difficulties. Furthermore, immigrants who arrive in adulthood often show poorer cognitive performance compared to those who immigrate earlier in life, with earlier generations displaying more pronounced deficits than their offspring, especially among those with low levels of acculturation. These sleep, circadian, and cognitive challenges may be even more severe in the aging zeroth generation. To address this knowledge gap, we have assembled a multidisciplinary team with expertise in sleep science, circadian rhythms, gerontology, immigrant health, and population health research, uniquely positioning us to conduct this study. The proposed project will establish a cohort of 100 older Chinese immigrants, aged 65 and above, who have joined their adult children in the US, with equal representation of men and women. Participants will undergo comprehensive assessments, including immigrant history, acculturative stress, and cognitive performance evaluations. Sleep and circadian rhythms will be measured using actigraphy, complemented by sleep diaries and validated questionnaires. This two-year pilot project has two specific aims: Aim 1 will investigate whether acculturative stress is associated with poorer sleep and circadian health, defined by worse subjective sleep quality, shorter sleep duration (subjective and objective), greater daytime sleepiness, and more disrupted rest-activity rhythms. Aim 2 will examine whether higher levels of acculturative stress are linked to worse cognitive performance, and whether sleep and circadian health moderates this relationship. This study will provide crucial insights into the cognitive aging of a vulnerable population, guiding future public health interventions and initiatives aimed at supporting aging immigrant populations.

NASA Headquarters

ROSES 2025: C.2 Solar System Science

NIAID - National Institute of Allergy and Infectious Diseases

Abstract Borrelia burgdorferi (Bb), the Lyme disease (LD) spirochete, cycles between an Ixodes spp. tick vector and a reservoir host, typically small rodents. To sustain its dual-host lifestyle, Bb employs sophisticated, yet parsimonious, regulatory mechanisms to reshape its transcriptome in response to tick and mammalian host signals. BosR–Bb's sole member of the FUR (ferric uptake regulator) family of regulators was initially described for its putative role in regulation of genes involved in Bb's oxidative stress response in vitro. It subsequently gained prominence from the discovery that it binds to the rpoS promoter and is required for RpoN-dependent expression of rpoS as well as RNAP-RpoS function in mammals. For the past two decades, the LD field has focused almost exclusively on BosR's role in the expression of rpoS and RpoS-regulated genes. BosR's Fur-like regulatory functions outside the RpoN/RpoS pathway remain a major knowledge gap. Our preliminary studies with our dialysis membrane chamber (DMCs) system for generating mammalian host-adapted Bb revealed that BosR regulates 82 genes independently of RpoS in mammals. We also found that BosR regulates 90 genes in vitro independently of RpoS, but only three of these are regulated by BosR in DMCs. Notably, none of the oxidative stress genes previously linked to BosR were dysregulated in ΔbosR under either condition. We further engineered an otherwise WT Bb strain expressing a BosR point mutant (R39A) with impaired DNA-binding activity and found that DNA-binding by BosR is essential for transcription of rpoS as well as its RpoS- independent function in DMCs. Collectively, these findings support our central hypothesis: Bb expresses distinct BosR regulons in ticks and mammals as a product of its Fur-like function that (i) is unrelated to the RpoN/RpoS pathway and (ii) involves differential promoter recognition in response to environmental signals. In our first Aim, we will define the BosR regulon in ticks using TBDCapSeq, a Bb-specific transcript enrichment methodology that we recently developed to investigate Bb gene expression in feeding ticks. Experiments in larvae are particularly relevant as they could prove that BosR has gene regulatory functions during a phase of the enzootic cycle when RpoS is OFF. Studies in this Aim will also establish whether BosR regulates distinct regulons in ticks and mammals. In our second Aim, we will examine the mechanism used by BosR to regulate gene expression independently of RpoS. Accordingly, we seek to establish that bind of BosR to a degenerate DNA motif gives rise to the BosR regulon(s). Unlike other Furs, BosR lacks a clearly defined regulatory metal binding site. Therefore, we will also investigate whether allosteric regulation of BosR, either by heme binding as suggested by AlphaFold3 structural modelling or interactions of BosR with c-di-GMP-liganded PlzA dictate distinct functions of BosR in ticks and mammals.

U.S. National Science Foundation

Safety, Security, and Privacy of Open-Source Ecosystems

NIAID - National Institute of Allergy and Infectious Diseases

Project Summary Host-adapted Salmonella enterica strains cause systemic infections and can persist in granulomas within host tissues for extended periods. Often asymptomatic, persistently infected hosts act as crucial reservoirs, silently transmitting the pathogen to new hosts. From a bacterial perspective, maintaining a persistent state is vital for survival in natural settings. Despite this importance, the molecular mechanisms governing Salmonella persistence and host-to-host transmission remain elusive. A clearer understanding of these processes could pave the way for pharmacological eradication of the Salmonella carrier state. Our overarching goal is to unravel how Salmonella enterica serovar Typhimurium (STm) maintains persistence in mammalian tissues, aiming to identify host pathways for preventive and therapeutic innovations. This proposal’s objective is to uncover how STm achieves persistence in mammalian tissues, with the aim of identifying host pathways amenable to preventive and therapeutic strategies. Specifically, we will examine granuloma dynamics and STm survival mechanisms in mesenteric lymph nodes (MLN). The primary objective of this research is to comprehensively characterize dynamics of STm colonization of MLN and to elucidate eosinophil functions that impact pathogen persistence. This will be investigated by examining the interactions between eosinophils and STm, both in vitro and in vivo (Aim 1), and exploring immune-pathogen interactions within distinct MLNs through spatial transcriptomics and immune profiling (Aim 2). Additionally, we aim to characterize the immunoregulatory functions of eosinophils that influence STm persistence in MLNs (Aim 3). Through these efforts, we aim to reveal critical insights into the interplay between host immune pathways and persistent Salmonella infections, informing future strategies to combat chronic bacterial carriage.

Scappoose Public Library District

The Scappoose Public Library will migrate to the integrating library system (ILS) that is currently in use by the St. Helens Public Library. This will enhance both libraries' infrastructure by providing a joint ILS that is cloud hosted, web based, and compatible with mobile devices. It will also enhance St. Helens patrons' discovery of ebooks as the new catalog will have the ability to check out ebooks directly. This merger coud serve as an intial building block for future union catalogs among other libraries in Columbia County.

U.S. National Science Foundation

Scholarships in STEM Network

Langston Hughes Performing Arts Institute

On September 21st and 22nd, LANGSTON will produce the first annual Seattle Black Nerd Fest: a free 2-day convention centering Black and brown community members interested in Afrofuturism, comic books, video games, STEM (Science, Tech, Engineering, Math), science fiction, fantasy, and more. Seattle Black Nerd Fest will center BIPOC voices within the nerd space - and provide an opportunity for BIPOC nerds, of all ages, to gather, meet creators, experts, and each other. Our convention will feature workshops, film screenings, panel discussions, meet and greets, mentoring sessions, vendors, interactive exhibits, and more.

Accurate Control Inc

Building and Facility Construction and Maintenance Services

Somers

Security System Upgrade - School

Groton

Senior Center Closed Circuit TV System for Public Area Monitoring

Employment and Training Administration (ETA)

SCSEP is a community service and work-based training program for older workers authorized in Title V of the Older Americans Act (OAA) and administered by USDOL/ETA. SCSEP is the only federally sponsored employment and training program targeted specifically to low-income older individuals. SCSEP provides subsidized, part-time, community service training for unemployed, low-income persons aged 55 or older who have poor employment prospects. Through this program, older workers have access to SCSEP services and employment training assistance through the One-Stop Career Center System. Program participants work an average of 20 hours a week and are paid the highest of the federal, state, or local minimum wage. Service priority is given to individuals meeting one or more of the following criteria: Is a veteran or a spouse of a veteran; Is 65 years of age or older; Has a disability; Has limited English proficiency; Has low literacy skills; Resides in a rural area; Has low employment prospects; Has failed to find employment after utilizing services provided under Title I of WIOA; Is homeless or at risk for homelessness; or Are formerly incarcerated or on supervision from release from prison or jail within five years of the date of initial eligibility determination. (Effective March 25, 2021, the 2020 reauthorization of the Older Americans Act (OAA) added this tenth characteristic category that has priority of service over those individuals who meet only the basic eligibility criteria related to age, income, and employment.)

NIAID - National Institute of Allergy and Infectious Diseases

SUMMARY RNA viruses pose a threat to organisms ranging from bacteria to humans, and thus all hosts need to recognize and defend themselves from these foreign invaders. While some principles of RNA virus recognition have been defined, primarily in mammalian systems, there remains a significant gap in knowledge as to how different hosts recognize the presence of an RNA virus. Much less is known about how simple metazoans, such as the model organism C. elegans, recognize virus infection. Studies in C. elegans have led to the discovery of multiple fundamental paradigms in biology, such as identification of caspase cell death pathways and RNA interference (RNAi). The discovery over a decade ago of Orsay virus (ORV), a positive strand RNA virus that is the first and only known natural virus of C. elegans to date, opened the door to virus-host interaction studies in this simple, multicellular invertebrate model system. Defining the host genes required for recognizing an RNA virus and the viral derived molecules that are sensed by C. elegans will provide novel insights into the evolution of self-versus-nonself discrimination. These studies could also lead to identification of novel viral recognition and signaling pathways that are broadly conserved. In mammals a family of cytoplasmic receptors that includes RIG- I and MDA5 senses the presence of intracellular RNA virus derived products. They then signal through additional proteins, such as MAVS, to activate transcription factors, including IRF3, IRF7, and NF-kB to induce an antiviral transcriptional response. C. elegans encodes DRH-1, a dicer related helicase that is homologous to RIG-I and MDA5, that is required for activation of the C. elegans transcriptional response, termed the intracellular pathogen response (IPR), to ORV infection. However, since C. elegans does not possess orthologs of MAVS, IRF3, IRF7 or NF-kB, it is not clear how the sensing of an RNA virus is transduced in C. elegans and what genes are involved. The viral derived molecule(s) that are recognized in C. elegans is also poorly defined. RIG-I binds viral dsRNA with a 5' triphosphate while MDA5 binds longer dsRNAs independent of the 5' terminus. In C. elegans, replication of ORV from a plasmid-based replicon system is sufficient to activate the IPR implicating an ORV replication product as the trigger. In preliminary data, we demonstrated that non-replicating ORV dsRNA produced by the endogenous C. elegans transcription machinery is sufficient to activate the IPR in vivo. This implies that viral dsRNA with 5' cap structure can be a trigger, providing the first evidence that DRH-1 maybe more similar to MDA5 than RIG-1. Thus, studies of DRH-1 may provide novel insights into the evolution and function of MDA5-like sensing proteins. Here, we will (1) define the host factors that recognize viral infection and are responsible for transducing that signal into a transcriptional response, and (2) determine the precise nature and characteristics of the viral ligand(s) that is recognized by C. elegans.

Friends of Seward Park

Western Hemlocks are dying in the northwest quadrant of the Seward Park's old-growth forest located at 5895 Lake Washington Blvd. The cause and mechanism of the decline are unknown. A survey of current tree health and geographic distribution is needed. The Friends of Seward Park will work with youth from CHOOSE 180 on a hemlock survey, collecting data and training the youth in field biology and data analysis. A protocol devised by PNW ecologists and pathologists and approved by Seattle Parks will guide our work. CHOOSE 180 is a community-centered program in partnership with the King County Prosecuting Attorney's Office to reduce race-based and economic disproportionality in the juvenile justice system. Friends of Seward Park will also collaborate with Forest Health Watch, provide data summaries, a preliminary analysis, and a short article submitted to an appropriate journal. This project will be completed by November 30, 2021.

City of Weston

Sewer Collection System Evaluation

City of Elgin

Sewer System Improvements

City of Vernonia

Sewer System Improvements - Construction

City of Saint Helens

Sewer System Improvements - Design

Greenwich

Sewer System Rehab

Greenwich

Sewer System Rehabilitation

City of Vernonia

Sewer System Repairs and Improvements