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2024

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Articles 12061 - 12090 of 13251

Full-Text Articles in Life Sciences

Formulation, Sensory Evaluation, And Physicochemical Assessment Of And Consumer Behavior Toward Novel Energy Bars, Ian Phillip Israelsen Jan 2024

Formulation, Sensory Evaluation, And Physicochemical Assessment Of And Consumer Behavior Toward Novel Energy Bars, Ian Phillip Israelsen

Graduate Theses, Dissertations, and Problem Reports (ETD)

The objectives of this study were to 1) formulate a novel energy bar containing significant macronutrients and calories per serving with favorable ratings from consumers; 2) analyze responses to a consumer preference survey and sensory evaluation of novel energy bars compared to a commercially available energy bar. For the first study, fourteen iterations of an energy bar were synthesized with differing protein sources (whey, soy, pea, hemp), and characteristic variations (nougat, chocolate truffle, peanut butter, double-date caramel). A shortbread base, date caramel, and chocolate coating were included in every bar. Sensory evaluations determined that the most liked variation overall was …


Evaluating The Efficacy Of The Archaeal Proteasome To Alleviate Protein-Misfolding Retinopathy, Celine Brooks Jan 2024

Evaluating The Efficacy Of The Archaeal Proteasome To Alleviate Protein-Misfolding Retinopathy, Celine Brooks

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nearly all neurodegenerative diseases (NDs) and some eye diseases are characterized by the presence of misfolded and aggregated proteins. The ubiquitin proteasome system (UPS) is responsible for degrading the majority of proteins including misfolded and aggregated proteins. However, in NDs the performance of the UPS is impaired, and this impairment partially comes from these protein aggregates inhibiting the proteasome. This inhibition leads to an accumulation of protein aggregates, more proteasomal inhibition, and fewer chaperones for newly synthesized proteins, triggering a collapse in proteostasis, which is thought to contribute to the pathogenesis of NDs. Consequently, stimulating proteasome function is being investigated …


Performance And Physiological Impacts Of Branched-Chain Amino Acid And Tryptophan Ratio Variations In Turkey Starter Diets Utilizing Concentrated Corn Proteins, Emily Blair Estanich Jan 2024

Performance And Physiological Impacts Of Branched-Chain Amino Acid And Tryptophan Ratio Variations In Turkey Starter Diets Utilizing Concentrated Corn Proteins, Emily Blair Estanich

Graduate Theses, Dissertations, and Problem Reports (ETD)

In Chapter 2, a study was designed to evaluate the effects of varying dietary branched-chain amino acids (BCAA) ratio in corn and soybean meal-based turkey starter diets. The BCAA leucine, isoleucine, and valine are considered indispensable amino acids needed for energy and stimulation of muscle protein synthesis via the mammalian target of rapamycin (mTOR) pathway. Imbalanced BCAA ratios can lead to antagonism and degradation of limiting BCAA, particularly in diets with excess leucine. Concentrated corn proteins contain high levels of leucine and can alter BCAA requirements; however, crystalline BCAA may be added to correct these ratios. This study aimed to …


Characterizing Prescribed Fire With Terrestrial Lidar In The New Jersey Pine Barrens, Samuel Rhule Stockton Jan 2024

Characterizing Prescribed Fire With Terrestrial Lidar In The New Jersey Pine Barrens, Samuel Rhule Stockton

Graduate Theses, Dissertations, and Problem Reports (ETD)

Prescribed burning has become a commonly used tool in the mitigation of wildfire, though monitoring the way it changes ecosystems has historically been a time-intensive process. Rapid change across ecosystems has necessitated advancements in remote sensing technologies to quantify the changes taking place. Single-scan terrestrial LiDAR scanning is one such method of monitoring these changes through the quantification of ecosystem structural characteristics. Acute disturbance events such as fire can transform the structure of an ecosystem, and by extension, change the way that ecosystem functions. The purpose of this study is to analyze the changes in vegetation density and distribution following …


A Balancing Act: Microrna Mediated Insect-Bacterial Homeostasis And The Tsetse Fly, Mason Hubbard Lee Jan 2024

A Balancing Act: Microrna Mediated Insect-Bacterial Homeostasis And The Tsetse Fly, Mason Hubbard Lee

Graduate Theses, Dissertations, and Problem Reports (ETD)

Microbial symbioses are ubiquitous across all kingdoms of life with broad and diverse impacts on the evolution of species. The sum of all microbes living in, on, or otherwise in close association with a host form the microbiota. In some cases, the development of a stable microbial association seems to have been necessary for the specialization of diet, as can be observed in numerous insect species, especially wood-eating, sap-feeding, and blood-feeding organisms. For the medically and economically tsetse fly (family Glossinidae), the mutualistic bacteria Wigglesworthia glossinidia is required for proper reproduction and supplementation of nutrients that the fly does not …


Cerebellar Feedback Effects On Responses To Conspecific Signals Of Different Frequencies In The Electrosensory System, Elora K. Shinn Jan 2024

Cerebellar Feedback Effects On Responses To Conspecific Signals Of Different Frequencies In The Electrosensory System, Elora K. Shinn

Graduate Theses, Dissertations, and Problem Reports (ETD)

Sensory systems in animals have evolved to translate physical stimuli into neural representations that, in turn, guide behavior. Feedback is critical in these processes, allowing organisms to filter redundant information and respond effectively to relevant stimuli. In humans, for example, the cerebellar flocculus provides feedback to the vestibulo-ocular reflex to stabilize eye movements during body rotation. In bats, the feedback during echolocation helps prioritize essential signals from the environment. In weakly electric fish, cerebellar feedback helps filter out redundant low-frequency modulations caused by conspecifics, enabling them to detect prey and other relevant signals. However, the influence of cerebellar feedback on …


Drosophila Parasitoids Go To Space: Unexpected Effects Of Spaceflight On Hosts And Their Parasitoids, Jennifer Chou, Johnny R. Ramroop, Amanda M. Saravia-Butler, Brian Wey, Matthew P. Lera, Medaya L. Torres, Mary Ellen Heavner, Janani Iyer, Siddhita D. Mhatre, Sharmila Bhattacharya, Shubha Govind Jan 2024

Drosophila Parasitoids Go To Space: Unexpected Effects Of Spaceflight On Hosts And Their Parasitoids, Jennifer Chou, Johnny R. Ramroop, Amanda M. Saravia-Butler, Brian Wey, Matthew P. Lera, Medaya L. Torres, Mary Ellen Heavner, Janani Iyer, Siddhita D. Mhatre, Sharmila Bhattacharya, Shubha Govind

Publications and Research

While fruit flies (Drosophila melanogaster) and humans exhibit immune system dysfunction in space, studies examining their immune systems’ interactions with natural parasites in space are lacking. Drosophila parasitoid wasps modify blood cell function to suppress host immunity. In this study, naive and parasitized ground and space flies from a tumor-free control and a blood tumor-bearing mutant strain were examined. Inflammation-related genes were activated in space in both fly strains. Whereas control flies did not develop tumors, tumor burden increased in the space-returned tumor-bearing mutants. Surprisingly, control flies were more sensitive to spaceflight than mutant flies; many of their …


A Gis Tool For Optimal Forage Species Selection, David B. Hannaway, Christopher Daly, Michael D. Halbleib, Linda Brewer, Sophie Baur, Chelsea Clark, Emilie Krecklow, Scott Bassett Jan 2024

A Gis Tool For Optimal Forage Species Selection, David B. Hannaway, Christopher Daly, Michael D. Halbleib, Linda Brewer, Sophie Baur, Chelsea Clark, Emilie Krecklow, Scott Bassett

IGC Proceedings (1977-2023)

To determine appropriate forage species for US ecoregions, geographic information technologies (GIS) are being used to create climatic and soil factor maps. Excel spreadsheets and RStudio are used to create response functions of forage species to minimum and maximum temperature, annual precipitation, soil pH, soil salinity, and salinity. National forage data and expert opinion will evaluate quantitative tolerances, seasonal yield profiles, and pollinator suitability. These maps and agronomic and livestock use information will be shared with forage specialists and farmers to provide alternatives for improved perenniality, increased diversity, and system circularity. Future work will include development and evaluation of climate …


The Impact Of Changing Joining Rates On The Western Australian Sheep Flock, Kate Pritchett Jan 2024

The Impact Of Changing Joining Rates On The Western Australian Sheep Flock, Kate Pritchett

Animal production and livestock research reports

Given the poor seasonal conditions and low prices experienced in 2023/24, the Western Australian (WA) sheep industry is experiencing a period of very poor industry sentiment often compared to that seen in the 1990’s following the collapse of the wool reserve price scheme.

These difficult times mean producers have had to make production decisions for their businesses which may have flow on effects for the entire state flock. One commonly discussed option by industry and consultants was to join less ewes to reduce the feed burden on farm and help mitigate losses due to low prices. This computer modelling aimed …


Loose Smut Of Barley And Its Management, Department Of Primary Industries And Regional Development, Western Australia Jan 2024

Loose Smut Of Barley And Its Management, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

The fungal disease loose smut of barley parasitises the host plant and produces masses of soot-like spores that infect the seed head, reducing the yield and quality of harvested grain.

Smut diseases are host specific, meaning that smut of one cereal crop will not infect others (for example, loose smut of barley does not infect wheat or oats).

In many cases grain receival points have low or zero tolerance of smut contaminated grain.


Identification Of Cellulose Synthase Structural Features Involved In Cellulose Synthesis Complex Formation, Jamie Lamkin Jan 2024

Identification Of Cellulose Synthase Structural Features Involved In Cellulose Synthesis Complex Formation, Jamie Lamkin

Open Access Dissertations

Cellulose is a microfibrillar polysaccharide component of plant cell walls and consists of bundles of β-1,4-linked glucan chains. In addition to being important for plant cell walls, cellulose is also used by humans for a variety of purposes such as biofuels and building materials. Cellulose is produced by the integral plasma membrane enzyme Cellulose Synthase (CESA) and multiple CESA proteins can combine to form a six-lobed rosette structure called a Cellulose Synthesis Complex (CSC). In seed plants CSCs appear to be hetero-oligomeric, comprising three different CESA isoforms. However some non-seed plants, such as the bryophyte Physcomitrium patens, can form …


Movement Behavior And Metapopulation Connectivity Of Stream Salamanders In Response To Disturbance Events, Kathryn M. Greene Jan 2024

Movement Behavior And Metapopulation Connectivity Of Stream Salamanders In Response To Disturbance Events, Kathryn M. Greene

Theses and Dissertations--Biology

Metapopulations are shaped by the dispersal between populations in a landscape. Disturbance events can disrupt this connectivity resulting in local population extinction. For my dissertation, I used a combination of empirical and theoretical techniques to examine dispersal in response to disturbance and assessed it’s population-level consequences. My research used capture-mark-recapture sampling techniques to evaluate stream salamander movement in response to (1) a supraseasonal drought and (2) mountaintop-removal-mining (MTR) and valley-filling (VF) and (3) agent-based simulation modeling to evaluate population extinction risk in response to varying dispersal and mortality rates.

First, I evaluated the effects of a supraseasonal drought, a severe …


Eliciting The Effect Free Roaming Cats Have On Native Hawaiian Wildlife Using Stable Isotope Analysis, Erin Salano Jan 2024

Eliciting The Effect Free Roaming Cats Have On Native Hawaiian Wildlife Using Stable Isotope Analysis, Erin Salano

Theses and Dissertations--Biology

This study measured the concentration of the stable isotopes Carbon and Nitrogen within the tissues of free-roaming and indoor cats on the Hawai’ian islands. This study aimed to determine whether cats are consuming more human provisioned or wild food sources and whether their diet is having a negative impact on endemic species; with a focus on assessing impacts on conserved bird populations. We hypothesized that human provisioned food sources have higher levels of carbon due to the amount of corn fillers within them, while wild food sources are more Nitrogen rich. We found that indoor and feral cats sampled from …


Navigating Asynchronous Online Learning: The Impacts Of Active Learning And Assigned Group Work On Student Motivation, Belonging, And Inclusion, Shea Elisabeth Carr Jan 2024

Navigating Asynchronous Online Learning: The Impacts Of Active Learning And Assigned Group Work On Student Motivation, Belonging, And Inclusion, Shea Elisabeth Carr

Theses and Dissertations--Biology

Motivation, belonging, and inclusion are all critical factors for student success but can be difficult to support in asynchronous online courses. Active learning and required group work have been shown to increase student motivation in in-person and synchronous online courses, but little is known about their impact in online asynchronous settings. This dissertation aimed to 1) evaluate the effect of active learning on student motivation in an online asynchronous setting and 2) evaluate the impact of assigned group work on student motivation and perceptions of belonging and inclusion within the context of an online, asynchronous physiology laboratory course. It was …


Elucidating The Effect Of Jak/Stat Signaling On Initiation Of Individualization, Sepideh Dadkhah Jan 2024

Elucidating The Effect Of Jak/Stat Signaling On Initiation Of Individualization, Sepideh Dadkhah

Theses and Dissertations--Biology

The JAK/STAT pathway is renowned for its involvement in diverse cellular processes, yet its precise role in the later events of spermiogenesis needs to be clarified. Spermiogenesis unfolds in the testis, where synchronized spermatid development occurs within two somatic cyst cells before being released into the seminal vesicle. Prior to this release, spermatid bundles undergo individualization, where F-actin investment cones accumulate at the nuclei of elongated spermatids and move down the length of the interconnected cysts, stripping away excess organelles and cytoplasm, resulting in individual spermatids that are then coiled and released into the testis lumen. Individualization depends on JAK/STAT …


Co-Divergence Of Lemur Hosts And Gut Microbiomes Across Multiple Evolutionary Scales, Mariah E. Donohue Jan 2024

Co-Divergence Of Lemur Hosts And Gut Microbiomes Across Multiple Evolutionary Scales, Mariah E. Donohue

Theses and Dissertations--Biology

This dissertation bridges micro- and macroevolutionary approaches to understand the co-diversification of animal hosts and their gut microbiomes at different evolutionary timescales. I examined these dynamics using wild lemurs, a diverse Primate clade endemic to the island of Madagascar.

First, I tested the relative effects of host phylogenetic relationships, diet, and habitat in shaping the gut microbiome through deep evolutionary time and across distinct microbial kingdoms. I designed a natural experiment sampling feces from rainforest and dry forest lemur communities with similar phylogenetic assemblages and considerable variation in dietary strategy. Then, I amplified and sequenced two metabarcoding genes, the V4 …


The Evolution Of The Metazoan Circadian Molecular Mechanism And The Conservation Of Canonical Circadian Elements, Olivia Waldridge Jan 2024

The Evolution Of The Metazoan Circadian Molecular Mechanism And The Conservation Of Canonical Circadian Elements, Olivia Waldridge

Theses and Dissertations--Biology

The temporal organization of biological activities through circadian rhythms is pivotal for the survival of organisms. Significant progress has been made in understanding the molecular foundations of animal circadian clocks through the characterization of key components such as Clock, Bmal1/Cycle(Cyc), Period (Per), Timeless, and Cryptochrome (Cry) in several model organisms. To determine the universality of this conservation, we investigated the sequences of these genes and their paralogs across 46 animal species that encompass multiple phyla in the metazoan kingdom to resolve the relative timing of duplication and loss events that have diversified core clock components in the metazoan kingdom. Using …


Reproductive Isolation And Gene Flow Across Space, Time And Genomes In Neodiprion Lecontei And N. Pinetum, Ashleigh Nicole Glover Jan 2024

Reproductive Isolation And Gene Flow Across Space, Time And Genomes In Neodiprion Lecontei And N. Pinetum, Ashleigh Nicole Glover

Theses and Dissertations--Biology

To explain biodiversity, evolutionary biologists must understand how independent lineages arise via the evolution of reproductive isolation during the speciation process. Hybridizing taxa provide an excellent opportunity to investigate the evolution of reproductive isolating barriers and genomic divergence, thereby enhancing our understanding of speciation. However, hybridization between diverging taxa can vary across geographic space, the genome, and time. Thus, understanding the factors that promote or inhibit hybridization can provide insight into the biotic, environmental, and genetic causes of divergence and gene flow. Importantly, the mechanisms responsible for generating variation in hybridization dynamics and the consequences of such hybridization remains unknown …


Cd8+ T Cell Metabolic Flexibility Elicited By Cd28-Ars2 Axis- Driven Alternative Splicing Of Pkm Supports Antitumor Immunity, G. Aaron Holling, Colin A. Chavel, Anand P. Sharda, Mackenzie M. Lieberman, Caitlin M. James, Shivana M. Lightman, Jason H. Tong, Guanxi Qiao, Tiffany R. Emmons, Thejaswini Giridharan, Shengqi Hou, Andrew M. Intlekofer, Richard M. Higashi, Teresa W. M. Fan, Andrew N. Lane, Kevin H. Eng, Brahm H. Segal, Elizabeth A. Repasky, Kevin P. Lee, Scott H. Olejniczak Jan 2024

Cd8+ T Cell Metabolic Flexibility Elicited By Cd28-Ars2 Axis- Driven Alternative Splicing Of Pkm Supports Antitumor Immunity, G. Aaron Holling, Colin A. Chavel, Anand P. Sharda, Mackenzie M. Lieberman, Caitlin M. James, Shivana M. Lightman, Jason H. Tong, Guanxi Qiao, Tiffany R. Emmons, Thejaswini Giridharan, Shengqi Hou, Andrew M. Intlekofer, Richard M. Higashi, Teresa W. M. Fan, Andrew N. Lane, Kevin H. Eng, Brahm H. Segal, Elizabeth A. Repasky, Kevin P. Lee, Scott H. Olejniczak

Markey Cancer Center Faculty Publications

Metabolic flexibility has emerged as a critical determinant of CD8+ T-cell antitumor activity, yet the mechanisms driving the metabolic flexibility of T cells have not been determined. In this study, we investigated the influence of the nuclear cap-binding complex (CBC) adaptor protein ARS2 on mature T cells. In doing so, we discovered a novel signaling axis that endows activated CD8+ T cells with flexibility of glucose catabolism. ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events. Among these effects, the CD28-ARS2 axis suppressed the expression of the …


The Carboxy Terminus Causes Interfacial Assembly Of Oleate Hydratase On A Membrane Bilayer, Christopher D. Radka, Christy R. Grace, Hale S. Hasdemir, Yupeng Li, Carlos C. Rodriguez, Patrick Rodrigues, Michael L. Oldham, M. Zuhaib Qayyum, Aaron Pitre, William J. Maccain, Ravi C. Kalathur, Emad Tajkhorshid, Charles O. Rock Jan 2024

The Carboxy Terminus Causes Interfacial Assembly Of Oleate Hydratase On A Membrane Bilayer, Christopher D. Radka, Christy R. Grace, Hale S. Hasdemir, Yupeng Li, Carlos C. Rodriguez, Patrick Rodrigues, Michael L. Oldham, M. Zuhaib Qayyum, Aaron Pitre, William J. Maccain, Ravi C. Kalathur, Emad Tajkhorshid, Charles O. Rock

Markey Cancer Center Faculty Publications

The soluble flavoprotein oleate hydratase (OhyA) hydrates the 9-cis double bond of unsaturated fatty acids. OhyA sub- strates are embedded in membrane bilayers; OhyA must remove the fatty acid from the bilayer and enclose it in the active site. Here, we show that the positively charged helix- turn-helix motif in the carboxy terminus (CTD) is responsible for interacting with the negatively charged phosphatidylgly- cerol (PG) bilayer. Super-resolution microscopy of Staphylo- coccus aureus cells expressing green fluorescent protein fused to OhyA or the CTD sequence shows subcellular localization along the cellular boundary, indicating OhyA is membrane- associated and the CTD sequence …


Cognitive Decline, Aβ Pathology, And Blood–Brain Barrier Function In Aged 5xfad Mice, Geetika Nehra, Sasivimon Promsan, Ruedeemars Yubolphan, Wijitra Chumboatong, Pornpun Vivithanaporn, Bryan J. Maloney, Anusorn Lungkaphin, Bjoern Bauer, Anika M. S. Hartz Jan 2024

Cognitive Decline, Aβ Pathology, And Blood–Brain Barrier Function In Aged 5xfad Mice, Geetika Nehra, Sasivimon Promsan, Ruedeemars Yubolphan, Wijitra Chumboatong, Pornpun Vivithanaporn, Bryan J. Maloney, Anusorn Lungkaphin, Bjoern Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background

Patients with Alzheimer’s disease (AD) develop blood–brain barrier dysfunction to varying degrees. How aging impacts Aβ pathology, blood–brain barrier function, and cognitive decline in AD remains largely unknown. In this study, we used 5xFAD mice to investigate changes in Aβ levels, barrier function, and cognitive decline over time.

Methods

5xFAD and wild-type (WT) mice were aged between 9.5 and 15.5 months and tested for spatial learning and reference memory with the Morris Water Maze (MWM). After behavior testing, mice were implanted with acute cranial windows and intravenously injected with fluorescent-labeled dextrans to assess their in vivo distribution in the …


Strategies For Improving The Performance Of Prediction Models For Response To Immune Checkpoint Blockade Therapy In Cancer, Tiantian Zeng, Jason Z. Zhang, Arnold Stromberg, Jin Chen, Chi Wang Jan 2024

Strategies For Improving The Performance Of Prediction Models For Response To Immune Checkpoint Blockade Therapy In Cancer, Tiantian Zeng, Jason Z. Zhang, Arnold Stromberg, Jin Chen, Chi Wang

Markey Cancer Center Faculty Publications

Immune checkpoint blockade (ICB) therapy holds promise for bringing long-lasting clinical gains for the treatment of cancer. However, studies show that only a fraction of patients respond to the treatment. In this regard, it is valu- able to develop gene expression signatures based on RNA sequencing (RNAseq) data and machine learning meth- ods to predict a patient’s response to the ICB therapy, which contributes to more personalized treatment strategy and better management of cancer patients. However, due to the limited sample size of ICB trials with RNAseq data available and the vast number of candidate gene expression features, it is …


Vaginal Lactobacillus Fatty Acid Response Mechanisms Reveal A Metabolite-Targeted Strategy For Bacterial Vaginosis Treatment, Paul C. Blainey, Seth M. Bloom, Douglas S. Kwon Jan 2024

Vaginal Lactobacillus Fatty Acid Response Mechanisms Reveal A Metabolite-Targeted Strategy For Bacterial Vaginosis Treatment, Paul C. Blainey, Seth M. Bloom, Douglas S. Kwon

Markey Cancer Center Faculty Publications

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). …


Oxidative Stress Alters Mitochondrial Homeostasis In Isolated Brain Capillaries, Gopal V. Velmurugan, Hemendra J. Vekaria, Anika M. S. Hartz, Björn Bauer, William Brad Hubbard Jan 2024

Oxidative Stress Alters Mitochondrial Homeostasis In Isolated Brain Capillaries, Gopal V. Velmurugan, Hemendra J. Vekaria, Anika M. S. Hartz, Björn Bauer, William Brad Hubbard

Markey Cancer Center Faculty Publications

Background

Neurovascular deficits and blood-brain barrier (BBB) dysfunction are major hallmarks of brain trauma and neurodegenerative diseases. Oxidative stress is a prominent contributor to neurovascular unit (NVU) dysfunction and can propagate BBB disruption. Oxidative damage results in an imbalance of mitochondrial homeostasis, which can further drive functional impairment of brain capillaries. To this end, we developed a method to track mitochondrial-related changes after oxidative stress in the context of neurovascular pathophysiology as a critical endophenotype of neurodegenerative diseases.

Methods

To study brain capillary-specific mitochondrial function and dynamics in response to oxidative stress, we developed an ex vivo model in which …


Elevated Free Cholesterol Levels Due To Impaired Reverse Cholesterol Transport Are A Risk Factor For Polymicrobial Sepsis In Mice, Qian Wang, Ling Guo, Dan Hao, Misa Ito, Chieko Mineo, Philip W. Shaul, Xiang-An Li Jan 2024

Elevated Free Cholesterol Levels Due To Impaired Reverse Cholesterol Transport Are A Risk Factor For Polymicrobial Sepsis In Mice, Qian Wang, Ling Guo, Dan Hao, Misa Ito, Chieko Mineo, Philip W. Shaul, Xiang-An Li

Markey Cancer Center Faculty Publications

Dysregulated lipid metabolism is commonly observed in septic patients, but how it contributes to sepsis remains largely unknown. Reverse cholesterol transport (RCT) is crucial for regulating cholesterol metabolism in circulation. During RCT, high-density lipoprotein collects cholesterol from peripheral tissues and transports it to the liver’s scavenger receptor BI (SR- BI), where SR-BI mediates the uptake of cholesteryl esters (CEs) from high-density lipoprotein for excretion via bile. In this study, we utilized AlbCreSR-BIfl/fl mice, a model with impaired RCT, to investigate the impact of RCT on sepsis. We found that AlbCreSR-BIfl/fl mice were significantly more susceptible to cecal ligation and puncture …


Nudcl2 Is Required For Cytokinesis By Stabilizing Rcc2 With Hsp90 At The Midbody, Xiaoyang Xu, Yuliang Huang, Feng Yang, Xiaoxia Sun, Rijin Lin, Jiaxing Feng, Mingyang Yang, Jiaqi Shao, Xiaoqi Liu, Tianhua Zhou, Shanshan Xie, Yuehong Yang Jan 2024

Nudcl2 Is Required For Cytokinesis By Stabilizing Rcc2 With Hsp90 At The Midbody, Xiaoyang Xu, Yuliang Huang, Feng Yang, Xiaoxia Sun, Rijin Lin, Jiaxing Feng, Mingyang Yang, Jiaqi Shao, Xiaoqi Liu, Tianhua Zhou, Shanshan Xie, Yuehong Yang

Markey Cancer Center Faculty Publications

Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. Midbody, a protein-dense organelle that forms at the intercellular bridge, is indispensable for success- ful cytokinesis. However, the regulatory mechanism of cytokinesis at the midbody still remains elusive. Here, we unveil a critical role for NudC-like protein 2 (NudCL2), a co-chaperone of heat shock protein 90 (Hsp90), in cytokinesis regulation by stabilizing regulator of chromosome condensation 2 (RCC2) at the midbody in mam- malian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinu- cleation, and midbody disorganization. Using iTRAQ-based …


Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options, Christa Corley, Ashley Craig, Safiyah M. Sadek, Julie A. Marusich, Samar N. Chehimi, Ashley M. White, Lexi J. Holdiness, Benjamin C. Reiner, Cassandra D. Gipson Jan 2024

Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options, Christa Corley, Ashley Craig, Safiyah M. Sadek, Julie A. Marusich, Samar N. Chehimi, Ashley M. White, Lexi J. Holdiness, Benjamin C. Reiner, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neuro- behavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical ex- periences in individuals …


Biliverdin Reductase-A Integrates Insulin Signaling With Mitochondrial Metabolism Through Phosphorylation Of Gsk3Β, Chiara Lanzillotta, Antonella Tramutola, Simona Lanzillotta, Viviana Greco, Sara Pagnotta, Caterina Sanchini, Silvia Di Angelantonio, Elena Forte, Serena Rinaldo, Alessio Paone, Francesca Cutruzzolà, Flavia Agata Cimini, Ilaria Barchetta, Maria Gisella Cavallo, Andrea Urbani, D. Allan Butterfield, Fabio Di Domenico, Bindu D. Paul, Marzia Perluigi, Joao M.N. Duarte Jan 2024

Biliverdin Reductase-A Integrates Insulin Signaling With Mitochondrial Metabolism Through Phosphorylation Of Gsk3Β, Chiara Lanzillotta, Antonella Tramutola, Simona Lanzillotta, Viviana Greco, Sara Pagnotta, Caterina Sanchini, Silvia Di Angelantonio, Elena Forte, Serena Rinaldo, Alessio Paone, Francesca Cutruzzolà, Flavia Agata Cimini, Ilaria Barchetta, Maria Gisella Cavallo, Andrea Urbani, D. Allan Butterfield, Fabio Di Domenico, Bindu D. Paul, Marzia Perluigi, Joao M.N. Duarte

Markey Cancer Center Faculty Publications

Brain insulin resistance links the failure of energy metabolism with cognitive decline in both type 2 Diabetes Mellitus (T2D) and Alzheimer’s disease (AD), although the molecular changes preceding overt brain insulin resistance remain unexplored. Abnormal biliverdin reductase-A (BVR-A) levels were observed in both T2D and AD and were associated with insulin resistance. Here, we demonstrate that reduced BVR-A levels alter insulin signaling and mitochondrial bioenergetics in the brain. Loss of BVR-A leads to IRS1 hyper-activation but dys- regulates Akt-GSK3β complex in response to insulin, hindering the accumulation of pGSK3βS9 into the mito- chondria. This event impairs oxidative phosphorylation and fosters …


Therapeutic Potential Of Berberine In Attenuating Cholestatic Liver Injury: Insights From A Psc Mouse Model, Yanyan Wang, Derrick Zhao, Lianyong Su, Yun-Ling Tai, Grayson W. Way, Jing Zeng, Qianhua Yan, Ying Xu, Xuan Wang, Emily C. Gurley, Xi-Qiao Zhou, Jinze Liu, Jinpeng Liu, Weidong Chen, Philip B. Hylemon, Huiping Zhou Jan 2024

Therapeutic Potential Of Berberine In Attenuating Cholestatic Liver Injury: Insights From A Psc Mouse Model, Yanyan Wang, Derrick Zhao, Lianyong Su, Yun-Ling Tai, Grayson W. Way, Jing Zeng, Qianhua Yan, Ying Xu, Xuan Wang, Emily C. Gurley, Xi-Qiao Zhou, Jinze Liu, Jinpeng Liu, Weidong Chen, Philip B. Hylemon, Huiping Zhou

Markey Cancer Center Faculty Publications

Background and aims

Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by progressive biliary inflammation and bile duct injury. Berberine (BBR) is a bioactive isoquinoline alkaloid found in various herbs and has multiple beneficial effects on metabolic and inflammatory diseases, including liver diseases. This study aimed to examine the therapeutic effect of BBR on cholestatic liver injury in a PSC mouse model (Mdr2 −/− mice) and eluci‑ date the underlying mechanisms.

Methods

Mdr2−/− mice (12–14 weeks old, both sexes) received either BBR (50 mg/kg) or control solution daily for eight weeks via oral gavage. Histological and serum biochemical …


Mechanisms Of Γδ T Cell Accumulation In Visceral Adipose Tissue With Aging, Sujata Mukherjee, Maria E. C. Bruno, Jason Oakes, Gregory S. Hawk, Arnold Stromberg, Donald A. Cohen, Marlene E. Starr Jan 2024

Mechanisms Of Γδ T Cell Accumulation In Visceral Adipose Tissue With Aging, Sujata Mukherjee, Maria E. C. Bruno, Jason Oakes, Gregory S. Hawk, Arnold Stromberg, Donald A. Cohen, Marlene E. Starr

Markey Cancer Center Faculty Publications

γδ T cells are resident in visceral adipose tissue (VAT) where they show an age- associated increase in numbers and contribute to local and systemic chronic inflammation. However, regulation of this population and mechanisms for the age-dependent accumulation are not known. In this study, we identified a progressive trend of γδ T cell accumulation in VAT over the lifespan in mice and explored physiological mechanisms contributing to accumulation. Using isochronic parabiotic pairs of wild-type (WT) and T cell receptor delta knockout (TCRδ KO) mice at young and old age, we confirmed that VAT γδ T cells are predominately a tissue-resident …