Digital Commons Network^™

Development Of Canagliflozin Nanocrystals Sublingual Tablets In The Presence Of Sodium Caprate Permeability Enhancer: Formulation Optimization, Characterization, Sammar Fathy Elhabal, Mohamed A El-Nabarawi, Nashwa Abdelaal, Mohamed Fathi Mohamed Elrefai, Shrouk A Ghaffar, Mohamed Mansour Khalifa, Passant M Mohie, Dania S Waggas, Ahmed Mohsen Elsaid Hamdan, Samar Zuhair Alshawwa, Essa M Saied, Nahla A Elzohairy, Tayseer Elnawawy, Rania A Gad, Nehal Elfar, Hanaa Mohammed, Mohammad Ahmad Khasawneh

Faculty, Staff and Students Publications

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants …

Prostate Safety Events During Testosterone Replacement Therapy In Men With Hypogonadism: A Randomized Clinical Trial, Shalender Bhasin, Thomas G Travison, Karol M Pencina, Michael O'Leary, Glenn R Cunningham, A Michael Lincoff, Steven E Nissen, M Scott Lucia, Mark A Preston, Mohit Khera, Nader Khan, Michael C Snabes, Xue Li, Catherine M Tangen, Kevin A Buhr, Ian M Thompson

Faculty, Staff and Students Publications

IMPORTANCE: The effect of testosterone replacement therapy (TRT) on the risk of prostate cancer and other adverse prostate events is unknown.

OBJECTIVE: To compare the effect of TRT vs placebo on the incidences of high-grade prostate cancers (Gleason score ≥4 + 3), any prostate cancer, acute urinary retention, invasive prostate procedures, and pharmacologic treatment for lower urinary tract symptoms in men with hypogonadism.

DESIGN, SETTING, AND PARTICIPANTS: This placebo-controlled, double-blind randomized clinical trial enrolled 5246 men (aged 45-80 years) from 316 US trial sites who had 2 testosterone concentrations less than 300 ng/dL, hypogonadal symptoms, and cardiovascular disease (CVD) or …

Contemporary Use Of Coronary Physiology In Cardiology, Ayman Elbadawi, Ramy Sedhom, Mohamed Ghoweba, Abdelazeem Mohamed Etewa, Waleed Kayani, Faisal Rahman

Faculty, Staff and Students Publications

Coronary angiography has a limited ability to predict the functional significance of intermediate coronary lesions. Hence, physiological assessment of coronary lesions, via fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), has been introduced to determine their functional significance. An accumulating body of evidence has consolidated the role of physiology-guided revascularization, particularly among patients with stable ischemic heart disease. The use of FFR or iFR to guide decision-making in patients with stable ischemic heart disease and intermediate coronary lesions received a class I recommendation from major societal guidelines. Nevertheless, the role of coronary physiology testing is less clear among certain …

Recommendations To Improve Quality Of Probiotic Systematic Reviews With Meta-Analyses, Lynne V Mcfarland, Gail Hecht, Mary E Sanders, Debra A Goff, Ellie J C Goldstein, Colin Hill, Stuart Johnson, Maryam R Kashi, Ravina Kullar, Maria L Marco, Daniel J Merenstein, Mathieu Millette, Geoffrey A Preidis, Eamonn M M Quigley, Gregor Reid, Seppo Salminen, Jason C Sniffen, Harry Sokol, Hania Szajewska, Daniel J Tancredi, Kristin Woolard

Faculty, Staff and Students Publications

Importance: Systematic reviews and meta-analyses often report conflicting results when assessing evidence for probiotic efficacy, partially because of the lack of understanding of the unique features of probiotic trials. As a consequence, clinical decisions on the use of probiotics have been confusing.

Objective: To provide recommendations to improve the quality and consistency of systematic reviews with meta-analyses on probiotics, so evidence-based clinical decisions can be made with more clarity.

Evidence review: For this consensus statement, an updated literature review was conducted (January 1, 2020, to June 30, 2022) to supplement a previously published 2018 literature search to identify areas where …

Characterization Of The Long-Distance Dispersal Kernel Of White-Tailed Deer And Evaluating Its Impact On Chronic Wasting Disease Spread In Wisconsin, Mennatallah Gouda

All Graduate Theses and Dissertations, Fall 2023 to Present

Chronic Wasting Disease (CWD) is a fatal, untreatable neurodegenerative disease that infects deer and related species. It is highly contagious and caused by abnormal malfunction and assembly of normal cellular proteins into aggregation-prone proteins. The Centers for Disease Control and prevention report that the prevalence of CWD in free-ranging deer in the US is still relatively low. However, in several states the infection rates exceed 1 deer in 10. Deer may uptake CWD from direct interaction with infected individuals or from the environment. Infected individuals shed CWD into the environment through feces, urine, saliva or carcasses, and long-distance dispersal of …

Geographic Variation In Blue Orchard Bee (Osmia Lignaria) Development And Performance As A Managed Pollinator In The Western United States, Morgan B. Scalici

All Graduate Theses and Dissertations, Fall 2023 to Present

Most flowering plants, including many cultivated food crops, will only produce well-developed fruits and seeds if pollen is transferred from one flower to another with the help of an animal pollinator. Honey bees are the most well-known and ubiquitous but are poor pollinators of some commercially important crops, or are in poor supply during crop bloom. In such cases, farmers will employ other managed pollinators such as bumble bees or solitary bees like mason and leafcutting bees. The blue orchard bee is North America's most agriculturally important native mason bee as effective pollinators of spring-blooming fruit crops. Differences in developmental …

Tropical Atlantic Temperature And Hydrologic Shifts During The Paleocene-Eocene Thermal Maximum, Chels Howard

All Graduate Theses and Dissertations, Fall 2023 to Present

The Paleocene-Eocene Thermal Maximum (PETM) is a geologic climate event that is studied heavily due to the similarities to anthropogenic climate change. This event occurred approximately 56 million years ago (Ma) and is characterized by a rapid release of carbon into the atmosphere, which resulted in an increase in temperature and a change in global climate events such as changes in patterns of evaporation and precipitation. We see this effect occurring in modern anthropogenic climate change due to the burning of fossil fuels releasing carbon dioxide (CO₂) into the atmosphere. In this study I use elemental data of …

Deep Learning With Effective Hierarchical Attention Mechanisms In Perception Of Autonomous Vehicles, Qiuxiao Chen

All Graduate Theses and Dissertations, Fall 2023 to Present

Autonomous vehicles need to gather and understand information from their surroundings to drive safely. Just like how we look around and understand what's happening on the road, these vehicles need to see and make sense of dynamic objects like other cars, pedestrians, and cyclists, and static objects like crosswalks, road barriers, and stop lines.

In this dissertation, we aim to figure out better ways for computers to understand their surroundings in the 3D object detection task and map segmentation task. The 3D object detection task automatically spots objects in 3D (like cars or cyclists) and the map segmentation task automatically …

The Influence Of Watershed Restoration Initiative Habitat Treatments On Mule Deer Relative Use And Fawn Production In Utah, Jaylin Solberg

All Graduate Theses and Dissertations, Fall 2023 to Present

Multiple factors could be the cause of mule deer (Odocoileus hemionus) population decline across the West such as an increase in non-native vegetation, human expansion, climate change, or a combination of these. Populations of mule deer generate substantial revenue for local communities and hold ecological, cultural, and social value. Therefore, wildlife researchers are increasing their efforts in improving environmental conditions that support mule deer growth. The Utah Department of Natural Resources and partners have taken proactive measures through the Utah Watershed Restoration Initiative (WRI) to improve mule deer habitats by restoring these environments to improve their quality for …

A Capstone Journey In Enterprise Software Consulting For Microsoft: How An Interdisciplinary Philosophy Fosters Critical Thinking And Promotes Cross-Functional Teamwork, Jacob Mccall

University Honors Theses

This capstone review thesis explores the application of strategic innovation and enterprise software with a Portland State University (PSU) School of Business Administration (SBA) interdisciplinary team consulting for Microsoft. Faced with improving pitch meetings with a new target audience of Chief Marketing Officers (CMOs), Microsoft's West Coast enterprise software sales team sought consultation from the PSU SBA 2023 Business Honors cohort. This text reflects on the precursors responsible for the consulting project’s success, including the university’s guiding principles, interdisciplinary philosophy, and applicable business practices. The final solution includes insights into CMO types, needs development, a marketing enterprise software visual sales …

How Beavers (Castor Canadensis) Affect Habitat Availability For Two Native Oregon Turtles: Actinemys Marmorata And Chrysemys Picta Bellii, Rodé Krige

University Honors Theses

Oregon is home to two native freshwater turtle species: the northwestern pond turtle and the western painted turtle. Both turtles are Oregon conservation strategy species with a status rating of sensitive, indicating declining populations. Oregon's decline in these turtle's populations is thought to be predominantly due to loss and degradation of habitat that results from development and urbanization. Beavers' ability to dam streams and create ponds may be creating habitat usable by turtles, but the relationship is under-studied. This study assessed water temperature, basking habitat, and overall turtle habitat suitability at beaver-dammed and control ponds in Portland, Oregon. Average basking …

The Effects Of Salt Marsh Restoration On The Hydrology Of Salt Marsh Channels, Isis Kontas

University Honors Theses

Salt marshes produce many ecosystem services, from water purification to protection from hurricanes. Despite their benefits, salt marshes have been impacted negatively by human activities. There are many salt marsh restoration projects that intend to bring back all ecological functions and services. Quantifiable measurements are needed to evaluate the effectiveness of such restoration efforts. Earlier work by Reagan Thomas demonstrated what happens to the hydrology of salt marsh channels when they are adjacent to restored salt marshes. This study builds on Thomas’ work and uses the sinuosity of channels as a quantitative, representative metric of salt marsh hydrology restoration effectiveness. …

Greater Socioenvironmental Risk Factors And Higher Chronic Pain Stage Are Associated With Thinner Bilateral Temporal Lobes, Lisa H Antoine, Burel R Goodin, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is …

Neurofibromin 1 Mutations Impair The Function Of Human Induced Pluripotent Stem Cell-Derived Microglia, Leonard D Kuhrt, Edyta Motta, Nirmeen Elmadany, Hannah Weidling, Raphaela Fritsche-Guenther, Ibrahim E Efe, Olivia Cobb, Jit Chatterjee, Lucy G Boggs, Marina Schnauß, Sebastian Diecke, Marcus Semtner, Corina Anastasaki, David H Gutmann, Helmut Kettenmann

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by germline mutations in the neurofibromin 1 (NF1) gene. Children with NF1 are prone to the development of multiple nervous system abnormalities, including autism and brain tumors, which could reflect the effect of NF1 mutation on microglia function. Using heterozygous Nf1-mutant mice, we previously demonstrated that impaired purinergic signaling underlies deficits in microglia process extension and phagocytosis in situ. To determine whether these abnormalities are also observed in human microglia in the setting of NF1, we leveraged an engineered isogenic series of human induced pluripotent stem cells to generate human …

Multi-Ancestry Study Of The Genetics Of Problematic Alcohol Use In Over 1 Million Individuals, Hang Zhou, Emma C Johnson, Pamela A F Madden, Andrew C Heath, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

Problematic alcohol use (PAU), a trait that combines alcohol use disorder and alcohol-related problems assessed with a questionnaire, is a leading cause of death and morbidity worldwide. Here we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals (European, N = 903,147; African, N = 122,571; Latin American, N = 38,962; East Asian, N = 13,551; and South Asian, N = 1,716 ancestries). We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine mapping improved the identification of likely causal variants. Prioritizing …

A Multisociety Delphi Consensus Statement On New Fatty Liver Disease Nomenclature, Mary E. Rinella, Samuel Klein, Et Al.

2020-Current year OA Pubs

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 …

Correlating Deep Learning-Based Automated Reference Kidney Histomorphometry With Patient Demographics And Creatinine, Nicholas Lucarelli, Brandon Ginley, Jarcy Zee, Sayat Mimar, Anindya S. Paul, Sanjay Jain, Seung Seok Han, Luis Rodrigues, Tezcan Ozrazgat-Baslanti, Michelle L. Wong, Girish Nadkarni, William L. Clapp, Kuang-Yu Jen, Pinaki Sarder

2020-Current year OA Pubs

KEY POINTS: The authors leverage the unique benefits of panoptic segmentation to perform the largest ever quantitation of reference kidney morphometry. Kidney features vary with age and sex; and glomeruli size may intricately link to creatinine, defying prior notions.

BACKGROUND: Reference histomorphometric data of healthy human kidneys are largely lacking because of laborious quantitation requirements. Correlating histomorphometric features with clinical parameters through machine learning approaches can provide valuable information about natural population variance. To this end, we leveraged deep learning (DL), computational image analysis, and feature analysis to associate the relationship of histomorphometry with patient age, sex, serum creatinine (SCr), …

Dietary And Supplemental Intake Of Vitamins C And E Is Associated With Altered Dna Methylation In An Epigenome-Wide Association Study Meta-Analysis, Amena Keshawarz, Roby Joehanes, Jiantao Ma, Gha Y. Lee, Ricardo Costeira, Pei-Chien Tsai, Olatz M. Masachs, Jordana T. Bell, Rory Wilson, Barbara Thorand, Juliane Winkelmann, Annette Peters, Jakob Linseisen, Melanie Waldenberger, Terho Lehtimäki, Pashupati P. Mishra, Mika Kähönen, Olli Raitakari, Mika Helminen, Carol A. Wang, Phillip E. Melton, Rae-Chi Huang, Craig E. Pennell, Therese A. O’Sullivan, Carolina Ochoa-Rosales, Trudy Voortman, Joyce B.J. Van Meurs, Kristin L. Young, Misa Graff, Yujie Wang, Douglas P. Kiel, Caren E. Smith, Paul F. Jacques, Daniel Levy

Research outputs 2022 to 2026

BACKGROUND: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. METHODS: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. RESULTS: …

Multi-Scale Mapping Of Australia’S Terrestrial And Blue Carbon Stocks And Their Continental And Bioregional Drivers, Lewis Walden, Oscar Serrano, Mingxi Zhang, Zefang Shen, James Z. Sippo, Lauren T. Bennett, Damien T. Maher, Catherine E. Lovelock, Peter I. Macreadie, Connor Gorham, Anna Lafratta, Paul S. Lavery, Luke Mosley, Gloria M. S. Reithmaier, Jeffrey J. Kelleway, Sabine Dittmann, Fernanda Adame, Carlos M. Duarte, John B. Gallagher, Pawel Waryszak, Paul Carnell, Sabine Kasel, Nina Hinko-Najera, Rakib Hassan, Madeline Goddard, Alice R. Jones, Raphael A. Viscarra Rossel

Research outputs 2022 to 2026

The soil in terrestrial and coastal blue carbon ecosystems is an important carbon sink. National carbon inventories require accurate assessments of soil carbon in these ecosystems to aid conservation, preservation, and nature-based climate change mitigation strategies. Here we harmonise measurements from Australia’s terrestrial and blue carbon ecosystems and apply multi-scale machine learning to derive spatially explicit estimates of soil carbon stocks and the environmental drivers of variation. We find that climate and vegetation are the primary drivers of variation at the continental scale, while ecosystem type, terrain, clay content, mineralogy and nutrients drive subregional variations. We estimate that in the …

“And I’M Going To Destroy You.”: Persona And Gender Performativity In Ernest Hemingway’S The Garden Of Eden, Nicole Minton

UNLV Theses, Dissertations, Professional Papers, and Capstones

While debate of Ernest Hemingway’s authorial masculine persona in connection to The Garden of Eden has been a point of interest in literary scholarship, no single work has tied together theory of gender performativity to persona. A borderline parodic display of masculine adventure has encouraged a one-dimensional view of Hemingway, who is viewed by audiences as the pinnacle of masculinity. However, this image is complicated by the publication of Eden, which reveals an author interested in gender and sexual identity fluidity. Rarely has a single text called into question so controversially an author’s public image. Eden showcases an empathetic …

Application Of Biochar For Antibiotic-Free Nutrient Recovery From Source-Separated Human Urine, Sayeda Ummeh Masrura

UNLV Theses, Dissertations, Professional Papers, and Capstones

In recent years, the application of biochar as a soil amendment has gained attention as a potential solution for nutrient management and environmental remediation. Biochar, a carbon-rich material produced through the pyrolysis of biomass under oxygen-limited conditions, exhibits unique physicochemical properties making it an effective sorbent for nutrients and contaminants. Its high surface area, porosity, and stability provide an ideal matrix for nutrient retention and release, as well as the immobilization of pollutants. One area of particular interest is the application of biochar for nutrient recovery from source-separated human urine. Source separation of urine has gained momentum as a sustainable …

Identification Of New 4-(6-Oxopyridazin-1-Yl)Benzenesulfonamides As Multi-Target Anti-Inflammatory Agents Targeting Carbonic Anhydrase, Cox-2 And 5-Lox Enzymes: Synthesis, Biological Evaluations And Modelling Insights, Waleed A Badawi, Mahmoud Rashed, Alessio Nocentini, Alessandro Bonardi, Mohammad M Abd-Alhaseeb, Sara T Al-Rashood, Giri Babu Veerakanellore, Taghreed A Majrashi, Eslam B Elkaeed, Bahaa Elgendy, Paola Gratteri, Claudiu T Supuran, Wagdy M Eldehna, Mohamed Elagawany

2020-Current year OA Pubs

Multiple inhibitions of CA, COX-2 and 5-LOX enzymes has been recognised as a useful strategy for the development of anti-inflammatory drugs that can avoid the disadvantages of using NSAIDs alone. Here, we report new pyridazine-based sulphonamides (

What Can The Plasma Proteome Tell Us About Platelets And (Vice Versa)?, Steven Bruzek, Marisol Betensky, Jorge Di Paola, Thomas Diacovo, Neil Goldenberg, Vera Ignjatovic

2020-Current year OA Pubs

Multi-omics approaches are being used increasingly to study physiological and pathophysiologic processes. Proteomics specifically focuses on the study of proteins as functional elements and key contributors to, and markers of the phenotype, as well as targets for diagnostic and therapeutic approaches. Depending on the condition, the plasma proteome can mirror the platelet proteome, and hence play an important role in elucidating both physiologic and pathologic processes. In fact, both plasma and platelet protein signatures have been shown to be important in the setting of thrombosis-prone disease states such as atherosclerosis and cancer. Plasma and platelet proteomes are increasingly being studied …

Human Parechovirus Central Nervous System Infection In A Young Infant Cohort, Aspasia Katragkou, Avni Sheth, Christina Gagliardo, Jessica Aquino, Niva Shah, Eberechi Nwaobasi-Iwuh, Christina Melchionne, Paige Black, Stephanie Chiu, Cecilia Di Pentima

Department of Pediatrics Faculty Papers

In 2022, a surge in cases of pediatric human parechovirus (HPeV) central nervous system infections in young infants was seen at our institution. Despite the dramatic increase in the number of cases seen that year, the clinical features of the illness were similar to prior years. The recent pediatric HPeV surge highlights the need to evaluate treatment options and standardize follow-up to better understand the long-term prognosis of infants with HPeV infection.

Slc6a1 Variant Pathogenicity, Molecular Function And Phenotype: A Genetic And Clinical Analysis, Arthur Stefanski, Marwan Shinawi, Et Al.

2020-Current year OA Pubs

Genetic variants in the SLC6A1 gene can cause a broad phenotypic disease spectrum by altering the protein function. Thus, systematically curated clinically relevant genotype-phenotype associations are needed to understand the disease mechanism and improve therapeutic decision-making. We aggregated genetic and clinical data from 172 individuals with likely pathogenic/pathogenic (lp/p) SLC6A1 variants and functional data for 184 variants (14.1% lp/p). Clinical and functional data were available for a subset of 126 individuals. We explored the potential associations of variant positions on the GAT1 3D structure with variant pathogenicity, altered molecular function and phenotype severity using bioinformatic approaches. The GAT1 transmembrane domains …

Primary Results Of The Saval Randomized Trial Of A Paclitaxel-Eluting Nitinol Stent Versus Percutaneous Transluminal Angioplasty In Infrapopliteal Arteries, Hans Van Overhagen, Patrick J Geraghty, Et Al.

2020-Current year OA Pubs

BACKGROUND: Effective and durable options for infrapopliteal artery revascularization for patients with chronic limb-threatening ischemia (CLTI) are limited.

METHODS: The SAVAL trial is a prospective, multicenter, randomized trial of patients with CLTI and infrapopliteal artery lesions with total lesion length ⩽ 140 mm, stenosis ⩾ 70%, and Rutherford category 4-5 assigned 2:1 to treatment with the SAVAL self-expandable paclitaxel drug-eluting stent (DES) or percutaneous transluminal angioplasty (PTA) with an uncoated balloon. The primary effectiveness endpoint was primary vessel patency (i.e., core lab-adjudicated duplex ultrasound-based flow at 12 months in the absence of clinically driven target lesion revascularization or surgical bypass …

Obesity And Outcomes Of Kawasaki Disease And Covid-19-Related Multisystem Inflammatory Syndrome In Children, Michael Khoury, William B Orr, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Obesity may affect the clinical course of Kawasaki disease (KD) in children and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19.

OBJECTIVE: To compare the prevalence of obesity and associations with clinical outcomes in patients with KD or MIS-C.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, analysis of International Kawasaki Disease Registry (IKDR) data on contemporaneous patients was conducted between January 1, 2020, and July 31, 2022 (42 sites, 8 countries). Patients with MIS-C (defined by Centers for Disease Control and Prevention criteria) and patients with KD (defined by American Heart Association criteria) were included. Patients with …

Lipidomic Analysis Of Porphyromonas Gingivalis Reveals Novel Glycerol Bisphosphoceramide, Phosphatidyl-, And Phosphoglycerol Dipeptide Lipid Families, Brian A Kleiboeker, Cheryl Frankfater, Mary E Davey, Fong-Fu Hsu

2020-Current year OA Pubs

Porphyromonas gingivalis, like other members of the phylum Bacteroidetes (synonym Bacteroidota), synthesizes several classes of dihydroceramides and peptidolipids. Using a similar strategy as that recently used to delimit the lipidome of its close relative Bacteroides fragilis, we applied linear ion trap multiple-stage mass spectrometry (linear ion trap MS

Endothelial Adam10 Utilization Defines A Molecular Pathway Of Vascular Injury In Mice With Bacterial Sepsis, Danielle N. Alfano, Mark J. Miller, Juliane Bubeck-Wardenburg

2020-Current year OA Pubs

The endothelium plays a critical role in the host response to infection and has been a focus of investigation in sepsis. While it is appreciated that intravascular thrombus formation, severe inflammation, and loss of endothelial integrity impair tissue oxygenation during sepsis, the precise molecular mechanisms that lead to endothelial injury remain poorly understood. We demonstrate here that endothelial ADAM10 was essential for the pathogenesis of Staphylococcus aureus sepsis, contributing to α-toxin-mediated (Hla-mediated) microvascular thrombus formation and lethality. As ADAM10 is essential for endothelial development and homeostasis, we examined whether other major human sepsis pathogens also rely on ADAM10-dependent pathways in …

Purification Of Modified Mammalian Actin Isoforms For In Vitro Reconstitution Assays, David J Kast, Silvia Jansen

2020-Current year OA Pubs

In vitro reconstitution assays using purified actin have greatly improved our understanding of cytoskeletal dynamics and their regulation by actin-binding proteins. However, early purification methods consisted of harsh conditions to obtain pure actin and often did not include correct maturation and obligate modification of the isolated actin monomers. Novel insights into the folding requirements and N-terminal processing of actin as well as a better understanding of the interaction of actin with monomer sequestering proteins such as DNaseI, profilin and gelsolin, led to the development of more gentle approaches to obtain pure recombinant actin isoforms with known obligate modifications. This review …