Digital Commons Network^™

Brugia Malayi And Other Filarial Parasite Species In Animals In Areas Endemic For Lymphatic Filariasis In Belitung District, Indonesia, Irina Diekmann, Taniawati Supali, Kerstin Fischer, Elisa Iskandar, Noviani Sugianto, Yossi Destani, Rahmat Alfian, Gary J. Weil, Peter U. Fischer

2020-Current year OA Pubs

BACKGROUND: Brugia malayi is the most common cause of lymphatic filariasis (LF) in Indonesia. A zoophilic ecotype that infects both humans and animals occur in Belitung District in Indonesia. The district received five annual rounds of mass drug administration (MDA) between 2006 and 2010 and passed three transmission assessment surveys (TAS) in subsequent years. However, a survey in five villages in 2021 showed a microfilaria (Mf) prevalence of 2.1% in humans. The reappearance of B. malayi infection in humans may be due to reintroduction from animal reservoirs. The goal of this study was to determine B. malayi prevalence in potential …

Eliminating The Ai Digital Divide By Building Local Capacity, Freya Gulamali, Thomas M. Maddox, Philip Payne, Et Al.

2020-Current year OA Pubs

Over the past few years, health delivery organizations (HDOs) have been adopting and integrating AI tools, including clinical tools for tasks like predicting risk of inpatient mortality and operational tools for clinical documentation, scheduling and revenue cycle management, to fulfill the quintuple aim. The expertise and resources to do so is often concentrated in academic medical centers, leaving patients and providers in lower-resource settings unable to fully realize the benefits of AI tools. There is a growing divide in HDO ability to conduct AI product lifecycle management, due to a gap in resources and capabilities (e.g., technical expertise, funding, data …

Gut Complement System: A New Frontier In Microbiota-Host Communication And Intestinal Homeostasis, Xianbin Tian, Lan Zhang, Xinyang Qian, Yangqing Peng, Fengyixin Chen, Sarah Bengtson, Zhiqing Wang, Meng Wu

2020-Current year OA Pubs

The gut microbiota plays a crucial role in maintaining intestinal homeostasis and influencing various aspects of host physiology, including immune function. Recent advances have highlighted the emerging importance of the complement system, particularly the C3 protein, as a key player in microbiota-host interactions. Traditionally known for its role in innate immunity, the complement system is now recognized for its interactions with microbial communities within the gut, where it promotes immune tolerance and protects against enteric infections. This Review explores the gut complement system as a possibly novel frontier in microbiota-host communication and examines its role in shaping microbial diversity, modulating …

Rtn4ip1 Is Required For The Final Stages Of Mitochondrial Complex I Assembly And Coq Biosynthesis, Monika Oláhová, Rachel M Guerra, Jack J Collier, Juliana Heidler, Kyle Thompson, Chelsea R White, Paulina Castañeda-Tamez, Alfredo Cabrera-Orefice, Robert N Lightowlers, Zofia M A Chrzanowska-Lightowlers, Alexander Galkin, Ilka Wittig, David J Pagliarini, Robert W Taylor

2020-Current year OA Pubs

A biochemical deficiency of mitochondrial complex I (CI) underlies approximately 30% of cases of primary mitochondrial disease, yet the inventory of molecular machinery required for CI assembly remains incomplete. We previously characterised patients with isolated CI deficiency caused by segregating variants in RTN4IP1, a gene that encodes a mitochondrial NAD(P)H oxidoreductase. Here, we demonstrate that RTN4IP1 deficiency causes a CI assembly defect in both patient fibroblasts and knockout cells, and report that RTN4IP1 is a bona fide CI assembly factor. Complexome profiling revealed accumulation of unincorporated ND5-module and impaired N-module production. RTN4IP1 patient fibroblasts also exhibited defective coenzyme Q biosynthesis, …

Nrf2 Immunobiology In Cancer: Implications For Immunotherapy And Therapeutic Targeting, Harit Panda, Natalie G Rowland, Caroline M Krall, Brittany M Bowman, Michael B Major, Paul Zolkind

2020-Current year OA Pubs

Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that acts as a key regulator in cellular defense mechanisms against oxidative stress and xenobiotics. NRF2 modulates the expression of over 200 genes involved in antioxidant response, drug metabolism, and cellular resilience. Constitutive activation of NRF2 is a common event in cancer and recent advances provide remarkable insights into the role of NRF2 in oncogenesis, immune evasion, and treatment resistance. This review aims to provide a comprehensive overview of the role of NRF2 in shaping the tumor immune microenvironment and the impact this has on clinical outcomes and treatment …

Ibrutinib Added To Standard Conditioning And As Maintenance Therapy Following Autologous Hematopoietic Stem Cell Transplantation For Relapsed Or Refractory Activated-B-Cell Type Diffuse Large B-Cell Lymphoma: Primary Analysis Of The Us Intergroup Double-Blind Randomized Phase Iii Study Alliance A051301/Bmt-Ctn 1201, Charalambos Andreadis, Brad S Kahl, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

To improve outcomes in relapsed or refractory activated B-cell type Diffuse Large B-cell Lymphoma (ABC-DLBCL), we launched a randomized phase 3 trial evaluating 2-year progression free survival (2yPFS) with the addition of ibrutinib to autologous transplant. Patients received ibrutinib 560 mg or placebo with conditioning and for 12 additional cycles. Accrual was adversely affected by implementation of the ABC classifier in this setting and the changing treatment landscape of DLBCL. In all, 39 patients on ibrutinib and 38 on placebo were evaluable. 2yPFS was 57.6% on ibrutinib versus 40.8% on placebo (

Family Income And Polygenic Scores Are Independently But Not Interactively Associated With Cognitive Performance Among Youth Genetically Similar To European Reference Populations, S E Paul, N M Elsayed, S M C Colbert, R Bogdan, A S Hatoum, D M Barch

2020-Current year OA Pubs

Cognitive abilities are heritable and influenced by socioeconomic status (SES). It is critical to understand the association between SES and cognition beyond genetic propensity to inform potential benefits of SES-based interventions and to determine if such associations vary across (i) cognitive domains, (ii) facets of SES, and/or (iii) genetic propensity for different aspects of cognition. We examined the contributions of neighborhood socioeconomic advantage, family income, and polygenic scores (PGS) for domains of cognition (i.e., general cognitive ability, executive function, learning and memory, fluid reasoning) in a sample of children (ages 9-10;

Spatial Multiomics Of Acute Myocardial Infarction Reveals Immune Cell Infiltration Through The Endocardium, Florian Wünnemann, Junedh M Amrute, Kory J Lavine, Et Al.

2020-Current year OA Pubs

Myocardial infarction (MI) continues to be a leading cause of death worldwide. Even though it is well established that the complex interplay between different cell types determines the overall healing response after MI, the precise changes in the tissue architecture are still poorly understood. In this study, we generated an integrative cellular map of the acute phase after murine MI using a combination of imaging-based transcriptomics (Molecular Cartography) and antibody-based highly multiplexed imaging (Sequential Immunofluorescence). This enabled us to evaluate cell type compositions and changes at subcellular resolution over time. We observed the recruitment of leukocytes to the infarcted heart …

Direct-To-Unit, Single-Visit, Curative-Intent Online Adaptive Stereotactic Ablative Radiotherapy For Early-Stage Lung Adenocarcinoma, Farnoush Forghani, Kendall Kiser, Eric Laugeman, Yao Hao, Robbie Beckert, Julie Rolfingsmeier, Clifford Robinson, Thomas Mazur, Pamela Samson

2020-Current year OA Pubs

BACKGROUND: Advancements in cone beam computed tomography (CBCT)-guided radiotherapy (RT) platforms have created new frontiers in adaptive radiotherapy (ART). This report describes the novel application of single-fraction adaptive stereotactic body radiotherapy (SBRT) for a 66-year-old woman with lung adenocarcinoma for whom a conventional RT workflow was impractical due to advanced Parkinson's disease with uncontrolled tremors.

CASE PRESENTATION: The patient presented with a 2.4 cm spiculated nodule in the left upper lobe (LUL) diagnosed as stage 1A3 lung adenocarcinoma. She declined surgery, and local radiation oncologists deemed SBRT unsafe due to her tremors. Our team proposed a direct-to-unit, single-visit SBRT treatment …

Ebola Virus Vp35 Nnlns Motif Modulates Viral Rna Synthesis And Mib2-Mediated Signaling, Grace Uwase, Priya Luthra, Olivia A Vogel, Jyoti Batra, Bruno A La Rosa, Kathleen C F Sheehan, Oam Khatavkar, Jacqueline E Payton, Robert A Davey, Nevan J Krogan, Christopher F Basler, Daisy W Leung, Gaya K Amarasinghe

2020-Current year OA Pubs

Ebola virus (EBOV) is a nonsegmented, negative-sense virus (NNSV) with a single-stranded RNA genome. EBOV encodes for a limited number of proteins and thus depends on host factors to facilitate viral replication and pathogenesis. Of the virus-encoded proteins, multifunctional EBOV VP35 (eVP35) is necessary for host immune evasion and viral RNA synthesis. Previous proteomics studies identified an interaction between eVP35 and the host E3 ubiquitin ligase Mindbomb 2 (MIB2). Here, we show how an NNLNS (Asn-Asn-Leu-Asn-Ser) motif (residues 201 to 205) within eVP35 serves as a binding site for MIB2. This motif is critical for eVP35-dependent inhibition of MIB2-mediated interferon …

Life-Moms: Effects Of Multicomponent Lifestyle Randomized Control Trial On Physical Activity During Pregnancy In Women With Overweight And Obesity, Hannah E Cabre, Debra Haire-Joshu, Alison G Cahill, Samuel Klein, Et Al.

2020-Current year OA Pubs

BACKGROUND: This report details the effect of LIFE-Mom's multicomponent lifestyle interventions on physical activity (PA) and inactivity time across pregnancy (2nd and 3rd trimesters) and their effect on gestational weight gain (GWG) and maternal/neonatal outcomes, a pre-specified secondary analysis.

METHODS: Pregnant people with BMI ≥ 25 kg/m

RESULTS: Although there were statistically significant differences in vigorous activity between the intervention and control group (p = .024), there were no clinically meaningful differences in PA. In the combined sample, moderate to vigorous PA (MVPA) significantly decreased across pregnancy (mean ± SD: 72.9 ± 29.1 min/day vs 63.9 ± 28.1 min/day; p …

Improving Data-Driven Gated (Ddg) Pet And Ct Registration In Thoracic Lesions: A Comparison Of Ai Registration And Ddg Ct, Tinsu Pan, M Allan Thomas, Yang Lu, Dershan Luo

2020-Current year OA Pubs

PURPOSE: Misregistration between CT and PET can result in mis-localization and inaccurate quantification of the tracer uptake in PET. Data-driven gated (DDG) CT can correct registration and quantification but requires a radiation dose of 1.3 mSv and 1 min of acquisition time. AI registration (AIR) does not require an additional CT and has been validated to improve registration and reduce the 'banana' misregistration artifacts around the diaphragm. We aimed to compare a validated AIR and DDG CT in registration and quantification of avid thoracic lesions misregistered in DDG PET scans.

METHODS: Thirty PET/CT patient data (23 with

RESULTS: DDG CT …

Development Of A Leucine-Rich Repeat-Containing Protein 15-Targeted Radio-Immunotheranostic Approach To Deplete Pro-Tumorigenic Mechanisms And Immunotherapy Resistance, Claire M Storey, Abbie Hasson, Diane Abou, Daniel Thorek, Et Al.

2020-Current year OA Pubs

Leucine-rich repeat containing 15 (LRRC15) has emerged as an attractive biomarker and target for cancer therapy. Transforming growth factor-β (TGFβ) induces the expression of this plasma membrane protein specifically in aggressive and treatment resistant tumor cells derived from mesenchymal stem cells, with minimal expression observed in non-neoplastic tissues. We have developed a humanized monoclonal antibody, DUNP19, that specifically binds with high affinity to a phylogenetically conserved LRRC15 epitope and is rapidly internalized upon LRRC15 binding. In multiple subcutaneous and orthotopic tumor xenograft mouse models, Lutetium-177 labeled DUNP19 ([

The Critical Human Pathogen Acinetobacter Baumannii Exhibits Light-Regulated Circadian Rhythms, Valentín Permingeat, Bárbara Edith Perez Mora, María Laura Migliori, Natalia Arana, Julia Fernández, María Belén Allasia, Melisa Luciana Lamberti, Gisela Di Venanzio, Ramiro Esteban Rodriguez, Mario Federico Feldman, Diego Andrés Golombek, María Alejandra Mussi

2020-Current year OA Pubs

Acinetobacter baumannii is recognized as the paradigm of multidrug-resistant superbug, topping the WHO priority list of critical human pathogens. Interestingly, it senses and responds to blue light, which modulates global aspects of its physiology, including pathogenicity. We hypothesized that light could serve as a signal to synchronize the bacterial physiology to the host's behavior and/or to the environment. At environmental temperatures, light regulation is mainly governed by the photoreceptor BlsA. In this work, we identified the existence of daily rhythms in blsA promoter activity displaying a robust response to light, as well as endogenous circadian rhythms in A. baumannii. In …

Long-Acting Recombinant Il-7 (Rhil-7-Hyfc) Enhances The Primary And Memory Neoantigen-Specific Immune Response To Breast Cancer Personalized Cancer Vaccines, Michael Chen, Thomas Kane, Ina Chen, Suangson Supabphol, Xiuli Zhang, Alexandra A Wolfarth, Donghoon Choi, Lijin Li, S Peter Goedegebuure, William E Gillanders

2020-Current year OA Pubs

No abstract provided.

Current States In Understanding Oligodendroglia-Mediated Neurological Issues In Neurofibromatosis Type 1 (Nf1), Benjamin E Aghoghovwia, Cheng-En Shen, Sabiha Bano, Nandini Shyamala, Alesandra Echeandia Marrero, Khushboo Irshad, Samer Sharafaldin, Nicole M Brossier, Yuan Pan

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1) is among the most common neurogenetic disorders and is associated with an increased risk of developing tumors in the nervous system. Additionally, up to 80% of patients with NF1 experience neurological complications, including deficits in attention, memory, and executive function. Significant effort has been dedicated to studying how NF1 mutations autonomously dysregulate neuronal function. Increasing evidence indicates that NF1 mutations also dysregulate the oligodendroglial lineage that contributes to neurological issues in NF1. Here, we summarize our current understanding of how NF1 mutations impact the oligodendroglial lineage homeostasis and plasticity. We also discuss gaps in knowledge, potential …

Motion Impact Score For Detecting Spurious Brain-Behavior Associations, Benjamin P Kay, David F Montez, Scott Marek, Joshua S Siegel, Babatunde Adeyemo, Timothy O Laumann, Athanasia Metoki, Roselyne J Chauvin, Andrew N Van, Vahdeta Suljic, Samuel R Krimmel, Ryland L Miller, Dillan J Newbold, Annie Zheng, Nicole A Seider, Kristen M Scheidter, Julia S Monk, Jarod L Roland, Evan M Gordon, Abraham Z Snyder, Deanna M Barch, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

In-scanner head motion introduces systematic bias to resting-state fMRI functional connectivity (FC) not completely removed by denoising algorithms. Researchers studying traits associated with motion (e.g. psychiatric disorders) need to know if their trait-FC relationships are impacted by residual motion to avoid reporting false positive results. We devised Split Half Analysis of Motion Associated Networks (SHAMAN) to assign a motion impact score to specific trait-FC relationships. SHAMAN distinguishes between motion causing overestimation or underestimation of trait-FC effects. We assessed 45 traits from n = 7270 participants in the Adolescent Brain Cognitive Development (ABCD) Study. After standard denoising with ABCD-BIDS and without …

In Vivo Crispr Screening In Head And Neck Cancer Reveals Uchl5 As An Immunotherapy Target, Cong Fu, Zahra Alipour, Douglas R Adkins, Rebecca D Chernock, Et Al.

2020-Current year OA Pubs

Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with a significant unmet need for enhancing immunotherapy response given current modest efficacy. Here, we perform an in vivo CRISPR screen in an HNSCC mouse model to identify immune evasion genes. We identify several regulators of immune checkpoint blockade (ICB) response, including the ubiquitin C-terminal hydrolase 5 (UCHL5). Loss of Uchl5 in tumors increases CD8

Lysosomal Lrrc8 Complex Impacts Lysosomal Ph, Morphology, And Systemic Glucose Metabolism, Ashutosh Kumar, Yonghui Zhao, Litao Xie, Rahul Chadda, John D Tranter, Ryan T Mikami, Nihil Abraham, Juan Hong, Ethan Feng, David R Rawnsley, Haiyan Liu, Gretchen Meyer, Abhinav Diwan, Rajan Sah, Et Al.

2020-Current year OA Pubs

The lysosome integrates anabolic signaling and nutrient sensing to regulate intracellular growth pathways. The leucine-rich repeat-containing 8 (LRRC8) channel complex forms a lysosomal anion channel and regulates PI3K-AKT-mTOR signaling, skeletal muscle differentiation, growth, and systemic glucose metabolism. Here, we define the endogenous LRRC8 subunits localized to a subset of lysosomes in differentiated myotubes. We show that LRRC8A affects leucine-stimulated mTOR; lysosome size; number; pH; expression of lysosomal proteins LAMP2, P62, and LC3B; and lysosomal function. Mutating an LRRC8A lysosomal targeting dileucine motif sequence (LRRC8A-L706A;L707A) in myotubes recapitulates the abnormal AKT signaling and altered lysosomal morphology and pH observed in LRRC8A …

Bedside Small-Bowel Challenge Vs. Fluoroscopic Series For Sbo: A Cost Effectiveness Analysis, Aravinda Krishna Ganapathy, Liam Cunningham, M Hunter Lanier, Selasi Nakhaima, Madelyn Thiel, Daniel Hoffman, Obeid Ilahi, David H Ballard, Vincent M Mellnick

2020-Current year OA Pubs

BACKGROUND: Small bowel obstruction (SBO) accounts for 12-16% of surgical hospital admissions and can lead to complications such as bowel ischemia. Traditional management requires transporting patients to the Radiology Department (RD) for a fluoroscopic small bowel series, occupying resources and time. This study evaluates the efficacy and efficiency of the Small Bowel Challenge Exam, a bedside alternative.

METHODS: A retrospective analysis was performed on 85 SBO patients from January 2018 to December 2023 at an academic tertiary care facility, comparing the traditional fluoroscopic series (37 patients) to the bedside Small Bowel Challenge Exam (48 patients). Key metrics analyzed included hospital …

Aggrebots: Configuring Ciliabots Through Guided, Modular Tissue Aggregation, Dhruv Bhattaram, Kian Golestan, Xuanshuo Zhang, Shihong Yang, Zhuowei Gong, Steven L Brody, Amjad Horani, Victoria A Webster-Wood, Amir Barati Farimani, Xi Ren

2020-Current year OA Pubs

Ciliated biobots (CiliaBots) are engineered tissues capable of self-actuated propulsion via exterior motile cilia. While correlations have been observed between CiliaBot motility and morphology, direct control of morphological features to deliver desired motility outcomes remains unexplored. Here, we describe the engineering of aggregated CiliaBots (AggreBots) to augment control over CiliaBot structural parameters and, consequently, motility patterns through guided, modular aggregation of human airway epithelial spheroids [referred to as CiliaBot building blocks (CBBs)]. Multi-CBB aggregation generated rod-, triangle-, and diamond-shaped AggreBots, altering tissue geometry without sacrificing surface cilia density or inter-CBB boundary fidelity. The further introduction of

Neutrophil Degranulation Is Increased At Seven Days After Human Intracerebral Hemorrhage, But Not At 72 H, And Correlates With Decreased Mir-3613 And Mir-3690, Kyle B Walsh, Miranda C Marion, Dengfeng Li, Hannah C Ainsworth, Amy Zinnia, Xiang Zhang, Stacie L Demel, Brady Williamson, David J Roh, Robert Campbell, Frederik Denorme, Daniel Woo, Carl D Langefeld

2020-Current year OA Pubs

BACKGROUND: The molecular mechanisms of inflammatory pathophysiology after intracerebral hemorrhage (ICH) are not well established. We report mRNA-seq and miRNA-seq in the peripheral blood of ICH patients with three serial samples during the first week after the stroke. METHODS: Twenty-seven ICH patients were enrolled via 24/7 screening and peripheral blood sampled at <  24 h (baseline), 72 h (+/-12 h), and 7 days (+/- 2 days) from last known normal. mRNA-seq and miRNA-seq were assessed for differential expression (DE) between the time point comparisons. Pathways identified via enrichment analysis (STRING, Reactome, Ingenuity Pathway Analysis) were tested via paired t-test and principal component analysis (PCA). Correlations between miRNA/mRNA pairs were computed. RESULTS: For DE mRNA at 72 h vs. baseline, the main enriched pathways pertained to neuronal function and synaptic transmission; prominent neuron-related genes from these pathways are also implicated in platelet activation. For 7 days vs. baseline, neutrophil degranulation and ribosomal biogenesis were the most enriched pathways; PCA also suggested neutrophil degranulation was the pathway most significantly different at 7 days vs. baseline compared with 72 h vs. baseline (p = 0.02). miR-3613 and miR-3690 had decreased expression at 7 days and were the miRNA most correlated with DE genes from the neutrophil degranulation pathway. CONCLUSION: Neutrophil degranulation was the prominent enriched pathway at 7 days after ICH and correlated with decreased miR-3613 and miR-3690. Further research is warranted of neutrophils in post-ICH inflammatory pathophysiology and functional validation studies of miR-3613 and miR-3690 as potential regulators of neutrophil degranulation after ICH.

Genetic Susceptibility To Oral And Atherosclerotic Cardiovascular Diseases Based On Dental And Heart Score Studies, Mariana Bezamat, Dylan J Baxter, Nandita Mukhopadhyay, Anum Saeed, Lei Liu, Lisa De Las Fuentes, Betsy Foxman, John R Shaffer, Daniel W Mcneil, Steven E Reis, Mary L Marazita

2020-Current year OA Pubs

Periodontal disease and dental caries are two oral conditions that have been associated with atherosclerotic cardiovascular disease (ASCVD). However, it is unclear if one of the key mechanisms involved in this association could be a shared genetic susceptibility. The goal of this study was to explore whether there is an intersection of genetic loci among individuals with comprehensive oral examinations and subclinical ASCVD screenings. We leveraged data from oral and medical examinations obtained from the Dental and Heart Strategies Concentrating on Risk Evaluation (Dental/Heart SCORE) projects. Genome-wide association studies (GWASs) were performed independently in 552 participants (aged 45-75 years). The …

A Protein-Proximity Screen Reveals Ebola Virus Co-Opts The Mrna Decapping Complex Through The Scaffold Protein Edc4, Callie J Donahue, Aditi S Kesari, Naveen Thakur, Ling Wang, Sarah Hulsey Stubbs, Caroline G Williams, Sandhya Bharti Sharma, Cara D Kirby, Daisy W Leung, Uma K Aryal, Christopher F Basler, Douglas J Lacount, Robert A Davey

2020-Current year OA Pubs

The interaction of host and Ebola virus (EBOV) proteins is required for establishing infection. In this study, we use proximity-dependent biotinylation to identify cellular proteins that bind to EBOV proteins encoded by six of the seven viral genes. Hits are computationally mapped onto a human protein-protein interactome and annotated with viral proteins, confirming known EBOV-host protein interactions and revealing previously undescribed interactions and processes. This approach efficiently arranges proteins into functional complexes associated with single viral proteins. Focused characterization of interactions between EBOV VP35 and the mRNA decapping complex shows that VP35 binds the scaffold protein EDC4 through the C-terminal …

Health And Climate At Cop29: Advancing Integration And Bridging Research Gaps, Rupa R Patel, Yevheniia Varyvoda, Hiba Baroud, Philip J Landrigan, Aminata Kilungo

2020-Current year OA Pubs

Climate and health science is a rapidly growing, interdisciplinary field and holds importance during intergovernmental climate adaptation and mitigation policy negotiations. The 29th session of the Conference of the Parties (COP) to the United Nations Framework Convention on Climate Change (UNFCCC) convened stakeholders for negotiations and scientific discourse. This viewpoint presents insights gained by the authors' participation at COP29 focused on health and climate. The authors analyze the evolving integration of health into the UNFCCC process, dissect the contributions and the role of the Research and Independent Non‑Governmental Organizations (RINGOs), a constituency to achieve this endeavor, and identify the key …

Fusion: A Web-Based Application For In-Depth Exploration Of Multi-Omics Data With Brightfield Histology, Samuel P Border, Sanjay Jain, Et Al.

2020-Current year OA Pubs

Spatial technologies examining the cell and tissue microenvironment at near single-cell resolution are revealing important molecular insights. However, few tools enable integrated, interactive analysis of spatial-omics with tissue morphology in the same functional tissue unit. Here, we present FUSION (Functional Unit State Identification in Whole Slide Images), a web-based platform for visualizing and analyzing spatial-omics data with high-resolution histology. FUSION provides workflows for assessing cell compositions, quantitative morphometrics, and comparative tissue analyses. We demonstrate applicability across spatial assays, including 10x Visium, Visium HD, 10x Xenium, Cell DIVE, and PhenoCycler, applied to healthy and diseased tissues from kidney, small intestine, lung, …

Evolutionary Loss Of An Antibiotic Efflux Pump Increases Pseudomonas Aeruginosa Quorum Sensing Mediated Virulence In Vivo, Sheryl E Fernandes, Humberto Ortega, Mylene Vaillancourt, Anna Clara M Galdino, Aleksandr Stotland, Kyu Shik Mun, Diane Aguilar, Yohei Doi, Janet S Lee, Elizabeth B Burgener, Jeffrey E Barrick, Jeffrey W Schertzer, Peter Jorth

2020-Current year OA Pubs

Antibiotic resistance is a threat to human health, yet recent work highlights how loss of resistance may drive pathogenesis in some bacteria. In two recent studies, we found that β-lactam antibiotics and nutrient stresses faced during infection selected for genetic inactivation of the Pseudomonas aeruginosa antibiotic efflux pump mexEFoprN. Unexpectedly, efflux pump mutations increased P. aeruginosa virulence during infection; however, neither the prevalence of mexEFoprN inactivating mutations in real human infections, nor the mechanisms driving increased virulence of efflux pump mutants are known. We hypothesized that human infection would select for virulence enhancing mutations. Using genome sequencing of clinical isolates, …

Association Of Chronic Conditions With Bladder Health In Women: Cross-Sectional Results From The Rise For Health Study, Camille P Vaughan, Gerald Mcgwin, Jean F Wyman, Siobhan Sutcliffe, Diane K Newman, Ariana L Smith, Colleen M Fitzgerald, Todd Rockwood, James Griffith, Sheila Gahagan, Alayne D Markland, Prevention Of Lower Urinary Tract Symptoms (Plus) Research Consortium

2020-Current year OA Pubs

INTRODUCTION: Women with multiple chronic conditions are more likely than women without them to report lower urinary tract symptoms (LUTS); understanding the association of common and coexisting chronic conditions with bladder health across adulthood may inform prevention efforts.

METHODS: Data were collected from May 2022 through December 2023 from a regionally representative cohort of community-dwelling adult women in the US. Chronic conditions were assessed by self-report and bladder health, and LUTS were measured using validated questionnaires. Analyses were limited to women aged 40 years or older and included multivariable linear and logistic regression models, adjusted for age, body mass index, …

Site-1 Protease Is A Negative Regulator Of Sarcolipin Promoter Activity, Isha Sharma, Meredith O Kelly, Katelyn Hanners, Ella S Shin, Muhammad G Mousa, Shelby Ek, Gretchen A Meyer, Rita T Brookheart

2020-Current year OA Pubs

The timed contraction and relaxation of myofibers in tissues such as the heart and skeletal muscle occur via the tightly regulated movement of calcium ions into and out of the sarcoplasmic reticulum (SR). In skeletal muscle, this phenomenon enables humans to exercise, perform day-to-day tasks, and to breathe. Sarcolipin, a small regulatory protein, prevents calcium ions from entering the SR by binding to and inhibiting SERCA, contributing to myofiber contraction. Disruptions in sarcolipin (SLN) expression are implicated in the pathophysiology of obesity and musculoskeletal disease. However, the mechanisms regulating sarcolipin expression are not clearly understood. We recently showed that site-1 …

Stable Cas9 Expression Regulates Cell Growth By Facilitating Mtorc2 Activation, Le Yu, Yi Jin, Jianfeng Chen, Zhichuan Zhu, Siyuan Su, Emily M Wilkerson, Joanna Gongora, Erica W Cloer, Michael B Major, Pengda Liu

2020-Current year OA Pubs

Clustered regularly interspaced short palindromic repeats (CRISPR), widely used for gene editing, relies on bacterial endonucleases like Cas9 to study gene functions and develop therapies. However, its potential effects on mammalian cellular behavior remain unclear. Here, we systematically profiled effects of stable Cas9 expression on growth of 32 cell lines spanning 9 cancer types and non-cancerous cells, finding growth alterations in a subset. To investigate mechanisms, we established the SpCas9 interactome in DU145 and MDA-MB-231 cells, both showing Cas9-enhanced growth, and identified ribosomal proteins as the top shared interactors. RNA-seq analysis revealed that Cas9 expression in DU145 cells activated PI3K …