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Full-Text Articles in Life Sciences

Exploring Nutritional Needs In Spinal Cord Injury: Dietitian Perspectives, Bowel Health, And Dietary Recommendations, Ayse Gul Zengul Jan 2025

Exploring Nutritional Needs In Spinal Cord Injury: Dietitian Perspectives, Bowel Health, And Dietary Recommendations, Ayse Gul Zengul

All ETDs from UAB

Spinal cord injury (SCI) is a global condition affecting millions of people and leading to life-altering health complications. It profoundly alters body composition and metabolic rate, which need to be addressed with SCI-specific nutritional strategies. Muscle atrophy, fat accumulation, and decreased energy expenditure often lead to secondary health complications such as chronic diseases and SCI-related health problems, including pressure injuries and bowel dysfunction. Although nutrition plays a critical role in SCI management, our understanding of specific dietary needs for this population remains incomplete. This dissertation aims to comprehensively investigate the nutritional challenges and needs of individuals with SCI, ultimately developing …


Evaluating The Contributions Of Nutrition Knowledge And Food Skills As Predictors Of Dietary Behavior, Diet Competence, And Diet Autonomy In Pre-Hypertensive Rural And Micropolitan Dwelling African American Adults In Alabama, Mary Catherine Robertson Lawson Jan 2025

Evaluating The Contributions Of Nutrition Knowledge And Food Skills As Predictors Of Dietary Behavior, Diet Competence, And Diet Autonomy In Pre-Hypertensive Rural And Micropolitan Dwelling African American Adults In Alabama, Mary Catherine Robertson Lawson

All ETDs from UAB

Introduction: African American (AA) adults living in rural, Southeastern communities experience disproportionately high rates of obesity-related chronic diseases. Many factors contributing to this health disparity are related to negative Social Determinants of Health that have individual and community level impacts. Nutrition knowledge (NK) and food skills (FS) are forms of health literacy that have been understudied in rural-dwelling AA adults. Understanding their relationships with self-perceived diet competence, autonomy, motivations, as well as diet behaviors and health outcomes could inform the development of future health research and policy. Methods: A scoping review was conducted to identify key trends and information gaps …


Unraveling The Kinetic Mechanisms Of Protein Unfolding And Translocation Catalyzed By Hsp100 Unfoldases, Jaskamaljot Kaur Banwait Jan 2025

Unraveling The Kinetic Mechanisms Of Protein Unfolding And Translocation Catalyzed By Hsp100 Unfoldases, Jaskamaljot Kaur Banwait

All ETDs from UAB

Escherichia coli ClpB and Saccharomyces cerevisiae Hsp104 are part of the Hsp100 family of proteins responsible for maintaining protein homeostasis in a cell during heat-stress conditions. Structurally, ClpB and Hsp104, in their active state, assemble into hexameric ring complexes with a hollow axial channel. Functionally, these enzymes are hypothesized to couple energy from ATP binding and hydrolysis to unfold protein substrates and translocate them through their axial channel. However, the molecular mechanisms of protein unfolding and translocation catalyzed by both ClpB and Hsp104 are not well understood. In this dissertation, we report the development of a single-turnover transient state kinetics …


Role Of Ring-Box E3 Ligases In Runx2 And Sp7 Protein Turnover During Osteoblast Differentiation, Abeera Sikandar Jan 2025

Role Of Ring-Box E3 Ligases In Runx2 And Sp7 Protein Turnover During Osteoblast Differentiation, Abeera Sikandar

All ETDs from UAB

The bone matrix synthesis by osteoblast during skeletogenesis is regulated by several transcription factors and signaling pathways. Runx2 and Sp7 are master regulators of osteoblast differentiation and bone formation. Deletion of both genes in mice results in the complete failure of ossification. In humans, Sp7 and Runx2 genes mutations cause osteogenesis imperfecta and cleidocranial dysplasia, respectively. The progression of osteoblast differentiation requires a coordinated and temporal expression of Runx2 and Sp7 genes. Posttranslational modifications regulate the cellular levels and function of Runx2 and Sp7 proteins. Ubiquitination controls protein turnover through targeted degradation. The multi-subunit SCF-complex is the largest class of …


St6gal1 Is Upregulated In Pancreatic Cancer Cells By Pro-Inflammatory Cytokines, Austin David Silva Jan 2025

St6gal1 Is Upregulated In Pancreatic Cancer Cells By Pro-Inflammatory Cytokines, Austin David Silva

All ETDs from UAB

The sialyltransferase ST6GAL1 is overexpressed in several cancers, including pancreatic ductal adenocarcinoma (PDAC). ST6GAL1 adds an α2-6-linked sialic acid to N-glycosylated membrane proteins, modifying their structure and function. Despite extensive research on how ST6GAL1 affects cell phenotype, the mechanisms regulating its expression remain largely unexplored. In this study, we investigated how two pro-inflammatory cytokines, IL-1β and IL-6, prevalent in the PDAC tumor microenvironment, regulate ST6GAL1 expression. We used the Suit-2 PDAC cell line and its metastatic subclones, S2-013 and S2-LM7AA, to monitor cytokine activity. Treatment with IL-1β or IL-6 increased ST6GAL1 protein and mRNA expression across all cell models. Specifically, …


Mechanistic Insights Of Translational Readthrough To Suppress Nonsense Mutations, Kari Thrasher Jan 2025

Mechanistic Insights Of Translational Readthrough To Suppress Nonsense Mutations, Kari Thrasher

All ETDs from UAB

A nonsense mutation is a point mutation in DNA that gives rise to a premature termination codon (PTC) in the open reading frame of the transcribed mRNA. Translation of this PTC-containing transcript terminates prematurely, leading to the creation of truncated non-functional protein. Translational readthrough is one therapeutic option being explored to suppress nonsense mutations that cause disease. Here, we further elucidate amino acid incorporation and the functional consequences of readthrough of nonsense mutations that cause cystic fibrosis. Additionally, we reveal the molecular mechanisms activated by a recently described small molecule readthrough agent, SRI- 41315. Finally, we discuss the various therapeutic …


Alternative Splicing In The Brain: Across Disease States, Sexes, Regions, And Cell Types, Emma Finn Jones Jan 2025

Alternative Splicing In The Brain: Across Disease States, Sexes, Regions, And Cell Types, Emma Finn Jones

All ETDs from UAB

Molecular phenotype heterogeneity is prevalent across multiple contexts and is mediated by mRNA expression differences and the gene and isoform level. Isoform-level mRNA complexity in the brain is essential for healthy neurodevelopment, and perturbations in AS are associated with many neurological and psychiatric disorders. While previous research has examined how AS changes in the brain, there is still a gap in using newer techniques to study these changes with greater specificity. Therefore, we address this gap by using long-read and scRNA-seq technologies to study isoform-level diversity in AS across four contexts (i.e., disease, sex, region, and cell type) in the …


Characterization Of The Roles Of U1-70k In Alternative Splicing And Nuclear Speckle Formation, Trenton Myers Paul Jan 2025

Characterization Of The Roles Of U1-70k In Alternative Splicing And Nuclear Speckle Formation, Trenton Myers Paul

All ETDs from UAB

RNA-binding proteins (RBPs) play critical roles in RNA processing and regulation. Among these RBPs, U1-70K is a key protein involved in RNA processing, nuclear speckle formation, and has implications in neurodegenerative diseases such as Alzheimer's. Despite its significance in transcription, RNA processing, nuclear speckle formation, and nonsense-mediated decay, studies on U1-70K have been limited primarily to its well-structured N-terminal domain due to challenges in solubilizing and expressing the full-length protein. In this dissertation, we address these challenges by optimizing cell strain and co expressing DnaK and DnaJ, enabling the successful expression, solubilization, and purification of full-length U1-70K. Using fluorescence polarization …


Cytotoxic, Genotoxic, And Metabolic Effects Of Dihydroxyacetone In Heart, Liver And Lung Models, Arlet Hernandez Jan 2025

Cytotoxic, Genotoxic, And Metabolic Effects Of Dihydroxyacetone In Heart, Liver And Lung Models, Arlet Hernandez

All ETDs from UAB

Dihydroxyacetone (DHA) is a triose sugar found as an active ingredient in sunless tanning products (STPs) and by-product in electronic cigarettes (e-cigarettes). DHA can rapidly be absorbed into cells and tissues and incorporated into several metabolic pathways through its conversion into dihydroxyacetone phosphate (DHAP). Previous studies have shown that DHA promotes cytotoxicity and genotoxicity primarily characterized in skin models. The extent of these effects in systemic models is highly cell-type specific. Here we investigate the cytotoxic, genotoxic, and metabolic effects of DHA across several cell models. First, we investigated the effects of DHA in a metabolically active cell line, hepatocellular …


The Evolutionary Ecology Of Reproductive System Variation In Haploid-Diploid Freshwater Red Macroalgae, Sarah Connelly Jan 2025

The Evolutionary Ecology Of Reproductive System Variation In Haploid-Diploid Freshwater Red Macroalgae, Sarah Connelly

All ETDs from UAB

Reproductive systems describe the relative rates of sexual versus asexual reproduction and selfing versus outcrossing, governing the transmission of genetic diversity between generations and shaping evolutionary responses to environmental change. Though sex has inherent costs, it contributes to the reproductive system for most eukaryotes, generating incredible life cycle diversity. Life cycles are expected to be correlated with different reproductive systems. Diploid life cycles should be associated with outcrossing, whereas life cycles with a long-lived haploid phase are hypothesized to be associated with selfing and asexual reproduction. To test this hypothesis, we used ten polymorphic microsatellite loci to genotype 311 gametophytes …


Targeted Exon Skipping Of Nf1 Exon 52 As A Mutation Specific Therapeutic For Neurofibromatosis Type 1, Cameron Lee Church Jan 2025

Targeted Exon Skipping Of Nf1 Exon 52 As A Mutation Specific Therapeutic For Neurofibromatosis Type 1, Cameron Lee Church

All ETDs from UAB

Modification of pre-mRNA splicing using antisense oligonucleotides (ASOs) can be used to skip one or more exons carrying pathogenic DNA sequence variants. Our previ-ously published data indicates NF1 exon 52 is a good target for exon skipping as a cDNA screen indicates an NF1 isoform lacking exon 52 maintains both high neurofi-bromin expression and the ability to suppress Ras activity. To develop an exon skipping approach, we designed antisense phosphorodiamidate morpholino oligomers (PMOs) to skip exon 52. Our lead PMO has a low IC50 of 45nM and is able to restore NF1 expres-sion and Ras-suppression in a cell line with …


Single Nucleus Multiomics Reveals The Drought-Driven Gene Regulatory Atlas In Arabidopsis, Jinbao Liu Jan 2025

Single Nucleus Multiomics Reveals The Drought-Driven Gene Regulatory Atlas In Arabidopsis, Jinbao Liu

All ETDs from UAB

The regulation of gene expression in plant responses to drought has been thoroughly in-vestigated in previous studies. Despite this, a detailed understanding of the cell type-specific regulatory mechanisms, encompassing multi-layered biological processes, is lack-ing. In this study, we report the use of single nucleus multiomic analysis in Arabidopsis seedlings in response to drought stress. Our single-nuclei RNA (snRNA) analysis deline-ated 14 distinct clusters representing major root and shoot cell types and discovered new cell type-specific drought markers. Integration of snRNA with single-nuclei ATAC (snATAC) data in leaf epidermis, root endodermis, and guard cells revealed accessible chromatin regions (ACRs)-linked genes predominantly …


Controlled By Disorder: Modifications To An Unstructured C-Terminal Region Alter Srsf1'S Intramolecular Interactions And Tendency To Phase Separate, Talia Fargason Jan 2025

Controlled By Disorder: Modifications To An Unstructured C-Terminal Region Alter Srsf1'S Intramolecular Interactions And Tendency To Phase Separate, Talia Fargason

All ETDs from UAB

The protein Serine-Arginine-rich Splicing Factor 1 (SRSF1) is essential in multiple stages of the mRNA lifecycle, including alternative splicing, nonsense-mediated decay, and nuclear export. SRSF1’s dysfunction is linked to cancers, viral evasion, and developmental disorders. Its function depends on interactions between structured and unstructured regions, modulated by phosphorylation. However, the unstructured regions, while critical for regulation, contribute to protein insolubility, hindering full-length studies. Prior to the work presented here, structural studies of SRSF1 were limited to analysis of its isolated domains. This dissertation develops new techniques to characterize SRSF1, focusing on its intermolecular interactions driving phase separation and intramolecular interactions …


Diurnal Function And Expression Of Aquaporins In The Mouse Kidney, Phi Hung Nguyen Jan 2025

Diurnal Function And Expression Of Aquaporins In The Mouse Kidney, Phi Hung Nguyen

All ETDs from UAB

Aquaporins (AQPs) are a family of proteins that play a major role in maintaining water homeostasis. Aquaporin 2 (AQP2) and aquaporin 3 (AQP3) are expressed in the collecting duct and regulated by the antidiuretic hormone arginine vasopressin (AVP) through the AVPR2 receptor. It is well known that biological circadian rhythms are critical for maintaining homeostasis. In both humans and rodents, the kidneys exhibit time-of-day-dependent changes in function. We hypothesized that there is a diurnal pattern in urine and/or plasma osmolality, and that this may reflect changes in kidney aquaporins in mice. Male and female C57BL/6J mice (10-11 weeks old) were …


Mammonc-Db: A Proteo-Genomic Platform For Comprehensive Breast Cancer Data Analysis, Integration And Visualization, Santhosh Kumar Karthikeyan Jan 2025

Mammonc-Db: A Proteo-Genomic Platform For Comprehensive Breast Cancer Data Analysis, Integration And Visualization, Santhosh Kumar Karthikeyan

All ETDs from UAB

ABSTRACT In 2024, breast cancer (BCa) emerged as the most prevalent cancer among women, accounting for 15% of fatalities in the United States. BCa is a multifaceted disease characterized by various molecular alterations associated with tumor initiation, progression, and metastasis. Clinically, different treatments such as endocrine therapy, chemotherapy, and anti-HER2 therapy are employed based on the molecular subtypes of breast cancer. Despite initial treatment responses, some cases experience recurrence due to therapy resistance. The application of next-generation sequencing techniques and data analysis has significantly enhanced our understanding of BCa biology, including its initiation and progression. By exploring BCa multi-omics data, …


Understanding The Insecticidal Toxin Xpta2: A Shift In Toxin Complex Biology, Cole Lorenza Martin Jan 2025

Understanding The Insecticidal Toxin Xpta2: A Shift In Toxin Complex Biology, Cole Lorenza Martin

All ETDs from UAB

Pore forming toxins (PFTs) belonging to the ABC toxin complex (Tc) family are responsible for targeting and translocating toxins into target cells. ABC toxins consist of three separate subunits, each subunit providing a vital role in the cytotoxic mechanism of the Tc. The A subunit or TcA is the largest subunit of the complex and contains the binding domains and the translocation channel that perforates the membrane. The B subunit or TcB functions as a gated linker that forms a cocoon with the TcC which houses the toxic peptide and subsequently gets translocated through the TcB and TcA into the …


Effects Of Whole-Food, Plant-Centered Diets On Glycemic Control, Medication Use, Ectopic Fat, And Cardiovascular Health In Adults With Type 2 Diabetes, Cody Hanick Jan 2025

Effects Of Whole-Food, Plant-Centered Diets On Glycemic Control, Medication Use, Ectopic Fat, And Cardiovascular Health In Adults With Type 2 Diabetes, Cody Hanick

All ETDs from UAB

Type 2 diabetes (T2D) is a global health and economic concern. Safe and effective treatments for T2D, including dietary approaches, are limited. Additionally, it remains unclear whether dietary carbohydrate quality or quantity matters more for managing T2D. Most nutrient-dense carbohydrate quality sources—such as fruit, vegetables, legumes, and whole grains—come from plant foods and are recommended for people with T2D by the American Diabetes Association. Furthermore, when these food groups are combined into a dietary pattern, a whole-food, plant-based (WFPB) diet is created. However, few studies have tested the effects of a WFPB diet or carbohydrate-rich food groups in people with …


Metal-Rich Lacustrine Sediments From Legacy Mining Perpetuate Copper Exposure To Aquatic-Riparian Food Webs, Brittany G. Perrotta, Karen A. Kidd, Kate M. Campbell, Marie-Noële Croteau, Tyler J. Kane, Amy Marcarelli, R Blaine Mccleskey, Gordon Paterson, Craig A. Stricker, David M. Walters Jan 2025

Metal-Rich Lacustrine Sediments From Legacy Mining Perpetuate Copper Exposure To Aquatic-Riparian Food Webs, Brittany G. Perrotta, Karen A. Kidd, Kate M. Campbell, Marie-Noële Croteau, Tyler J. Kane, Amy Marcarelli, R Blaine Mccleskey, Gordon Paterson, Craig A. Stricker, David M. Walters

Michigan Tech Publications

Historic copper mining left a legacy of metal-rich tailings resulting in ecological impacts along and within Torch Lake, an area of concern in the Keweenaw Peninsula, Michigan, USA. Given the toxicity of copper to invertebrates, this study assessed the influence of this legacy on present day nearshore aquatic and terrestrial ecosystems. We measured the metal (Co, Cu, Ni, Zn, Cd) and metalloid (As) concentrations in sediment, pore water, surface water, larval and adult insects, and two riparian spider taxa collected from Torch Lake and a nearby reference lake. Overall, elevated metal and metalloid concentrations, particularly Cu, were measured in all …


Scproatlas: An Atlas Of Multiplexed Single-Cell Spatial Proteomics Imaging In Human Tissues, Xi Liu, Pora Kim, Liyu Huang, Kexin Huang, Xiaobo Zhou Jan 2025

Scproatlas: An Atlas Of Multiplexed Single-Cell Spatial Proteomics Imaging In Human Tissues, Xi Liu, Pora Kim, Liyu Huang, Kexin Huang, Xiaobo Zhou

Faculty, Staff and Student Publications

Spatial proteomics can visualize and quantify protein expression profiles within tissues at single-cell resolution. Although spatial proteomics can only detect a limited number of proteins compared to spatial transcriptomics, it provides comprehensive spatial information with single-cell resolution. By studying the spatial distribution of cells, we can clearly obtain the spatial context within tissues at multiple scales. Spatial context includes the spatial composition of cell types, the distribution of functional structures, and the spatial communication between functional regions, all of which are crucial for the patterns of cellular distribution. Here, we constructed a comprehensive spatial proteomics functional annotation knowledgebase, scProAtlas (https://relab.xidian.edu.cn/scProAtlas/#/), …


Aspdb: An Integrative Knowledgebase Of Human Protein Isoforms From Experimental And Ai-Predicted Structures, Rongbin Li, Wenbo Chen, Chiamaka S Diala, Meer A Ali, Yi Xu, Albon Wu, Sayed-Rzgar Hosseini, Erfei Bi, Hongyu Zhao, Pora Kim, W Jim Zheng Jan 2025

Aspdb: An Integrative Knowledgebase Of Human Protein Isoforms From Experimental And Ai-Predicted Structures, Rongbin Li, Wenbo Chen, Chiamaka S Diala, Meer A Ali, Yi Xu, Albon Wu, Sayed-Rzgar Hosseini, Erfei Bi, Hongyu Zhao, Pora Kim, W Jim Zheng

Faculty, Staff and Student Publications

Alternative splicing is a crucial cellular process in eukaryotes, enabling the generation of multiple protein isoforms with diverse functions from a single gene. To better understand the impact of alternative splicing on protein structures, protein-protein interaction and human diseases, we developed ASpdb (https://biodataai.uth.edu/ASpdb/), a comprehensive database integrating experimentally determined structures and AlphaFold 2-predicted models for human protein isoforms. ASpdb includes over 3400 canonical isoforms, each represented by both experimentally resolved and predicted structures, and >7200 alternative isoforms with AlphaFold 2 predictions. In addition to detailed splicing events, 3D structures, sequence variations and functional annotations, ASpdb uniquely offers comparative analyses and …


Metsdb: A Knowledgebase Of Cancer Metastasis At Bulk, Single-Cell And Spatial Levels, Zhaocan Zhang, Zhennan Lu, Pora Kim, Xiaobo Zhou, Liyu Huang Jan 2025

Metsdb: A Knowledgebase Of Cancer Metastasis At Bulk, Single-Cell And Spatial Levels, Zhaocan Zhang, Zhennan Lu, Pora Kim, Xiaobo Zhou, Liyu Huang

Faculty, Staff and Student Publications

Cancer metastasis, the process by which tumour cells migrate and colonize distant organs from a primary site, is responsible for the majority of cancer-related deaths. Understanding the cellular and molecular mechanisms underlying this complex process is essential for developing effective metastasis prevention and therapy strategies. To this end, we systematically analysed 1786 bulk tissue samples from 13 cancer types, 988 463 single cells from 17 cancer types, and 40 252 spots from 45 spatial slides across 10 cancer types. The results of these analyses are compiled in the metsDB database, accessible at https://relab.xidian.edu.cn/metsDB/. This database provides insights into alterations in …


Crisprofft: Comprehensive Database Of Crispr/Cas Off-Targets, Pora Kim, Qianqian Song, Xiaona Liu, Xiaobo Zhou Jan 2025

Crisprofft: Comprehensive Database Of Crispr/Cas Off-Targets, Pora Kim, Qianqian Song, Xiaona Liu, Xiaobo Zhou

Faculty, Staff and Student Publications

The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated protein) programmable nuclease system continues to evolve, with in vivo therapeutic gene editing increasingly applied in clinical settings. However, off-target effects remain a significant challenge, hindering its broader clinical application. To enhance the development of gene-editing therapies and the accuracy of prediction algorithms, we developed CRISPRoffT (https://ccsm.uth.edu/CRISPRoffT/). Users can access a comprehensive repository of off-target regions predicted and validated by a diverse range of technologies across various cell lines, Cas enzyme variants, engineered sgRNAs (single guide RNAs) and CRISPR editing systems. CRISPRoffT integrates results of off-target analysis from 74 studies, encompassing …


Land-Use Effects On Soil Organic Matter And Related Soil Properties In A Mixed Agricultural–Forest Landscape Of Central Wisconsin, Usa, Kathryn L. Hofmeister, Gwen Feitl, Kaylee Tackett, Leah Fleury, Lucas E. Nave Jan 2025

Land-Use Effects On Soil Organic Matter And Related Soil Properties In A Mixed Agricultural–Forest Landscape Of Central Wisconsin, Usa, Kathryn L. Hofmeister, Gwen Feitl, Kaylee Tackett, Leah Fleury, Lucas E. Nave

Michigan Tech Publications

Soil organic matter (SOM) influences a wide range of ecosystem processes, including nutrient cycling, water movement, plant productivity, and biodiversity. In agricultural landscapes, adjacent land uses often differ in SOM contents and related soil properties, such as soil organic carbon (SOC) stocks, but the direction and magnitude of these effects are inconsistent across studies. We assessed how land uses differed in SOM and related properties in a representative US Midwest agricultural–forest landscape to support land-use and management decisions by local landowners and producers. We measured SOM, bulk density (Db), root biomass, and pH, and estimated SOC stocks, in a Typic …


The Manipulation Of Odor Availability Of Training Aids Used In Detection Canine Training, Katylynn B. Sloan, Michele N. Maughan, Caitlin E. Sharpes, Robin R. Greubel, Shawna F. Gallegos, Aleksandr E. Miklos, Lindsay D. Waldrop Jan 2025

The Manipulation Of Odor Availability Of Training Aids Used In Detection Canine Training, Katylynn B. Sloan, Michele N. Maughan, Caitlin E. Sharpes, Robin R. Greubel, Shawna F. Gallegos, Aleksandr E. Miklos, Lindsay D. Waldrop

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Detection canines can identify numerous substances for which they have been trained. Historically, and a point of ongoing contention, detection canine threshold (i.e., sensitivity or limit of detection) training has primarily focused on changing the weight of the training aid substance used. There has been minimal focus on other principles, such as surface area, confinement, and temperature, which can be manipulated to affect odor availability. That said, trainers have been manipulating odor availability for years without necessarily understanding the governing scientific principles. The aim of this review is to highlight the principles that control odor availability of a substance and …


Dimensionality Reduction For Visualizing Spatially Resolved Profiling Data Using Spasne, Yuansheng Zhou, Chen Tang, Xue Xiao, Xiaowei Zhan, Tao Wang, Lin Xu Jan 2025

Dimensionality Reduction For Visualizing Spatially Resolved Profiling Data Using Spasne, Yuansheng Zhou, Chen Tang, Xue Xiao, Xiaowei Zhan, Tao Wang, Lin Xu

Faculty, Staff and Student Publications

Background: Spatially resolved profiling technologies to quantify transcriptomes, epigenomes, and proteomes have been emerging as groundbreaking methods for comprehensive molecular characterizations. Dimensionality reduction and visualization is an essential step to analyze and interpret spatially resolved profiling data. However, state-of-the-art dimensionality reduction methods for single-cell sequencing data, such as the t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP), were not tailored for spatially resolved profiling data.

Results: Here we developed a spatially resolved t-SNE (SpaSNE) method to integrate both spatial and molecular information. We applied it to a variety of public spatially resolved profiling datasets that were …


The Association Of The Chemotherapy Response Score And Homologous Recombination Deficiency In Patients Undergoing Interval Tumor Reductive Surgery Following Neoadjuvant Chemotherapy, Roni Nitecki Wilke, Jinsong Liu, Shannon Neville Westin, Bryan M Fellman, Travis T Sims, Kelly Rangel, Jose Alejandro Rauh-Hain, Karen H Lu, Anil K Sood, Nicole D Fleming Jan 2025

The Association Of The Chemotherapy Response Score And Homologous Recombination Deficiency In Patients Undergoing Interval Tumor Reductive Surgery Following Neoadjuvant Chemotherapy, Roni Nitecki Wilke, Jinsong Liu, Shannon Neville Westin, Bryan M Fellman, Travis T Sims, Kelly Rangel, Jose Alejandro Rauh-Hain, Karen H Lu, Anil K Sood, Nicole D Fleming

Faculty, Staff and Student Publications

Objectives: In patients undergoing interval tumor reductive surgery, a good response to neoadjuvant chemotherapy may limit available tumor for homologous recombination deficiency testing. The objective of this study was to assess whether the chemotherapy response score predicts homologous recombination status.

Methods: We identified patients with advanced epithelial ovarian cancer (diagnosed January 2019 to 20 June 2023) who received neoadjuvant chemotherapy, underwent interval surgery, and for whom a chemotherapy response score was reported (1=no or minimal tumor response, 2=appreciable tumor response, 3=complete or near complete response with no residual tumor). Comparisons were made using ANOVAs or Kruskal-Wallis test for continuous variables …


Cansar 2024-An Update To The Public Drug Discovery Knowledgebase, Phillip W Gingrich, Rezvan Chitsazi, Ansuman Biswas, Chunjie Jiang, Li Zhao, Kevin M Brammer, Zhigang Shu, David S Maxwell, Jeffrey A Tacy, Ioan L Mica, Michael Darkoh, Patrizio Di Micco, Kaitlyn P Russell, Paul Workman, Bissan Al-Lazikani Jan 2025

Cansar 2024-An Update To The Public Drug Discovery Knowledgebase, Phillip W Gingrich, Rezvan Chitsazi, Ansuman Biswas, Chunjie Jiang, Li Zhao, Kevin M Brammer, Zhigang Shu, David S Maxwell, Jeffrey A Tacy, Ioan L Mica, Michael Darkoh, Patrizio Di Micco, Kaitlyn P Russell, Paul Workman, Bissan Al-Lazikani

Faculty, Staff and Student Publications

canSAR (https://cansar.ai) continues to serve as the largest publicly available platform for cancer-focused drug discovery and translational research. It integrates multidisciplinary data from disparate and otherwise siloed public data sources as well as data curated uniquely for canSAR. In addition, canSAR deploys a suite of curation and standardization tools together with AI algorithms to generate new knowledge from these integrated data to inform hypothesis generation. Here we report the latest updates to canSAR. As well as increasing available data, we provide enhancements to our algorithms to improve the offering to the user. Notably, our enhancements include a revised ligandability classifier …


Intrinsic Adaptive Plasticity In Mouse And Human Sensory Neurons, Lisa A Mcilvried, John Smith Del Rosario, Melanie Y Pullen, Andi Wangzhou, Tayler D Sheahan, Richard A Slivicki, Theodore J Price, Bryan A Copits, Robert W Gereau Jan 2025

Intrinsic Adaptive Plasticity In Mouse And Human Sensory Neurons, Lisa A Mcilvried, John Smith Del Rosario, Melanie Y Pullen, Andi Wangzhou, Tayler D Sheahan, Richard A Slivicki, Theodore J Price, Bryan A Copits, Robert W Gereau

Faculty, Staff and Student Publications

In response to changes in activity induced by environmental cues, neurons in the central nervous system undergo homeostatic plasticity to sustain overall network function during abrupt changes in synaptic strengths. Homeostatic plasticity involves changes in synaptic scaling and regulation of intrinsic excitability. Increases in spontaneous firing and excitability of sensory neurons are evident in some forms of chronic pain in animal models and human patients. However, whether mechanisms of homeostatic plasticity are engaged in sensory neurons of the peripheral nervous system (PNS) is unknown. Here, we show that sustained depolarization (induced by 24-h incubation in 30 mM KCl) induces compensatory …


Urban Sensing In The Era Of Large Language Models, Ce Hou, Fan Zhang, Yong Li, Haifeng Li, Gengchen Mai, Ling Yao, Yao Yao, Song Gao, Min Chen, Yu Liu Jan 2025

Urban Sensing In The Era Of Large Language Models, Ce Hou, Fan Zhang, Yong Li, Haifeng Li, Gengchen Mai, Ling Yao, Yao Yao, Song Gao, Min Chen, Yu Liu

Faculty, Staff and Student Publications

Urban sensing has become increasingly important as cities evolve into the centers of human activities. Large language models (LLMs) offer new opportunities for urban sensing based on commonsense and worldview that emerged through their language-centric framework. This paper illustrates the transformative impact of LLMs, particularly in the potential of advancing next-generation urban sensing for exploring urban mechanisms. The discussion navigates through several key aspects, including enhancing knowledge transfer between humans and LLM, urban mechanisms awareness, and achieve automated decision-making with LLM agents. We emphasize the potential of LLMs to revolutionize urban sensing, offering a more comprehensive, efficient, and in-depth understanding …


Circakb: A Comprehensive Knowledgebase Of Circadian Genes Across Multiple Species, Seung-Hee Yoo, Zheng Chen, Zhiwei Ji Jan 2025

Circakb: A Comprehensive Knowledgebase Of Circadian Genes Across Multiple Species, Seung-Hee Yoo, Zheng Chen, Zhiwei Ji

Faculty, Staff and Student Publications

Circadian rhythms, which are the natural cycles that dictate various physiological processes over a 24-h period, have been increasingly recognized as important in the management and treatment of various human diseases. However, the lack of sufficient data and reliable analysis methods have been a major obstacle to understanding the bidirectional interaction between circadian variation and human health. We have developed CircaKB, a comprehensive knowledgebase of circadian genes across multiple species. CircaKB is the first knowledgebase that provides systematic annotations of the oscillatory patterns of gene expression at a genome-wide level for 15 representative species. Currently, CircaKB contains 226 time-course transcriptome …