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2021

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Articles 601 - 630 of 862

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Protease Oma1 Modulates Mitochondrial Bioenergetics And Ultrastructure Through Dynamic Association With Micos Complex, Martonio Ponte Viana, Roman M. Levytskyy, Ruchika Anand, Andreas S. Reichert, Oleh Khalimonchuk Feb 2021

Protease Oma1 Modulates Mitochondrial Bioenergetics And Ultrastructure Through Dynamic Association With Micos Complex, Martonio Ponte Viana, Roman M. Levytskyy, Ruchika Anand, Andreas S. Reichert, Oleh Khalimonchuk

Department of Biochemistry: Faculty Publications

Remodeling of mitochondrial ultrastructure is a process that is critical for organelle physiology and apoptosis. Although the key players in this process—mitochondrial contact site and cristae junction organizing system (MICOS) and Optic Atrophy 1 (OPA1)—have been characterized, the mechanisms behind its regulation remain incompletely defined. Here, we found that in addition to its role in mitochondrial division, metallopeptidase OMA1 is required for the maintenance of intermembrane connectivity through dynamic association with MICOS. This association is independent of OPA1, mediated via the MICOS subunit MIC60, and is important for stability of MICOS and the intermembrane contacts. The OMA1-MICOS relay is required …


Valtoco® (Diazepam Nasal Spray) For The Acute Treatment Of Intermittent Stereotypic Episodes Of Frequent Seizure Activity, Elyse M. Cornett, Sam N. Amarasinghe, Alexis Angelette, Tunde Abubakar, Adam M. Kaye, Alan David Kaye, Elisa E. Neuchat, Ivan Urits, Omar Viswanath Feb 2021

Valtoco® (Diazepam Nasal Spray) For The Acute Treatment Of Intermittent Stereotypic Episodes Of Frequent Seizure Activity, Elyse M. Cornett, Sam N. Amarasinghe, Alexis Angelette, Tunde Abubakar, Adam M. Kaye, Alan David Kaye, Elisa E. Neuchat, Ivan Urits, Omar Viswanath

School of Pharmacy Faculty Articles

Valtoco® is a new FDA-approved nasal spray version of diazepam indicated for the treatment of acute, intermittent, and stereotypic episodes of frequent seizure activity in epilepsy patients six years of age and older. Although IV and rectal diazepam are already used to treat seizure clusters, Valtoco® has less variability in plasma concentration compared to rectal diazepam. Furthermore, the intranasal administration of Valtoco® is more convenient and less invasive than rectal or IV diazepam, making it ideal for self-administration outside of a hospital setting. Multiple clinical trials have taken place comparing Valtoco® to the oral, rectal, and IV forms of diazepam. …


Effects Of Drying, Packaging Conditions And Storage Time On Proximate Composition Of Chia Seeds (Salvia Hispanica), Ashura Katunzi-Kilewela, Leonard Rweyemamu, Oscar Kibazohi, Lilian Kaale Feb 2021

Effects Of Drying, Packaging Conditions And Storage Time On Proximate Composition Of Chia Seeds (Salvia Hispanica), Ashura Katunzi-Kilewela, Leonard Rweyemamu, Oscar Kibazohi, Lilian Kaale

Tanzania Journal of Science

The effects of drying, packaging conditions and storage time on proximate composition of chia seeds were investigated. Chia seeds were dried at 63 °C for 30 min (low-temperature long time–LTLT) and at 75 °C for 30 s (high-temperature short time-HTST) using dry oven, air/vacuum-packed and stored for ten weeks. The effect of heat processing (drying) on chia seeds had significant difference (p < 0.05) in ash, fiber and fat contents while there was no significant difference (p > 0.05) in moisture and protein contents. Except for fiber content, there was no significant difference (p > 0.05) in moisture, ash, fat and protein of chia seeds dried at LTLT and HTST before storage. During storage time, there was …


Rasagiline Effects On Glucose Metabolism, Cognition, And Tau In Alzheimer’S Dementia, Dawn C. Matthews, Aaron Ritter, Ronald G. Thomas, Randolph D. Andrews, Ana S. Lukic, Carolyn Revta, Jefferson W. Kinney, Babak Tousi, James B. Leverenz, Howard Fillit, Kate Zhong, Howard H. Feldman, Jeffrey Cummings Feb 2021

Rasagiline Effects On Glucose Metabolism, Cognition, And Tau In Alzheimer’S Dementia, Dawn C. Matthews, Aaron Ritter, Ronald G. Thomas, Randolph D. Andrews, Ana S. Lukic, Carolyn Revta, Jefferson W. Kinney, Babak Tousi, James B. Leverenz, Howard Fillit, Kate Zhong, Howard H. Feldman, Jeffrey Cummings

Integrated Health Sciences Faculty Research

Background: A Phase II proof of concept (POC) randomized clinical trial was conducted to evaluate the effects of rasagiline, a monoamine oxidase B (MAO-B) inhibitor approved for Parkinson disease, in mild to moderate Alzheimer's disease (AD). The primary objective was to determine if 1 mg of rasagiline daily for 24 weeks is associated with improved regional brain metabolism (fluorodeoxyglucose–positron emission tomography [FDG-PET]) compared to placebo. Secondary objectives included measurement of effects on tau PET and evaluation of directional consistency of clinical end points. Methods: This was a double-blind, parallel group, placebo-controlled, community-based, three-site trial of 50 participants randomized 1:1 to …


The Rac-Gef Tiam1 Promotes Dendrite And Synapse Stabilization Of Dentate Granule Cells And Restricts Hippocampal-Dependent Memory Functions, Jinxuan Cheng, Federico Scala, Francisco A Blanco, Sanyong Niu, Karen Firozi, Laura Keehan, Shalaka Mulherkar, Emmanouil Froudarakis, Lingyong Li, Joseph G Duman, Xiaolong Jiang, Kimberley F Tolias Feb 2021

The Rac-Gef Tiam1 Promotes Dendrite And Synapse Stabilization Of Dentate Granule Cells And Restricts Hippocampal-Dependent Memory Functions, Jinxuan Cheng, Federico Scala, Francisco A Blanco, Sanyong Niu, Karen Firozi, Laura Keehan, Shalaka Mulherkar, Emmanouil Froudarakis, Lingyong Li, Joseph G Duman, Xiaolong Jiang, Kimberley F Tolias

Faculty, Staff and Students Publications

The dentate gyrus (DG) controls information flow into the hippocampus and is critical for learning, memory, pattern separation, and spatial coding, while DG dysfunction is associated with neuropsychiatric disorders. Despite its importance, the molecular mechanisms regulating DG neural circuit assembly and function remain unclear. Here, we identify the Rac-GEF Tiam1 as an important regulator of DG development and associated memory processes. In the hippocampus, Tiam1 is predominantly expressed in the DG throughout life. Global deletion of Tiam1 in male mice results in DG granule cells with simplified dendritic arbors, reduced dendritic spine density, and diminished excitatory synaptic transmission. Notably, DG …


Methylation Of The D2 Dopamine Receptor Affects Binding With The Human Regulatory Proteins Par-4 And Calmodulin, Alexander Bowitch, Ansuman Sahoo, Andrea M. Clark, Christiana Ntangka, Krishna K. Raut, Paul Gollnick, Michael C. Yu, Steven M. Pascal, Sarah E. Walker, Denise M. Ferkey Feb 2021

Methylation Of The D2 Dopamine Receptor Affects Binding With The Human Regulatory Proteins Par-4 And Calmodulin, Alexander Bowitch, Ansuman Sahoo, Andrea M. Clark, Christiana Ntangka, Krishna K. Raut, Paul Gollnick, Michael C. Yu, Steven M. Pascal, Sarah E. Walker, Denise M. Ferkey

Chemistry & Biochemistry Faculty Publications

No abstract provided.


Virucidal Activity Of Chlorine Dioxide Gas For Reduction Of Coronavirus On Surfaces And Ppe, Jeffrey Driver, George Lukasik, Marie Bourgeois, Patricia Tam, Raymond Harbison Feb 2021

Virucidal Activity Of Chlorine Dioxide Gas For Reduction Of Coronavirus On Surfaces And Ppe, Jeffrey Driver, George Lukasik, Marie Bourgeois, Patricia Tam, Raymond Harbison

School of Pharmacy Faculty Articles

A coronavirus (SARS-CoV-2) has caused a global pandemic and associated morbidity and mortality resultant from COVID-19. As a result of efforts to control direct (person to person) and indirect (contaminated objects, surfaces, indoor air) transmission of the virus, various interventions have been evaluated. Studies were conducted to evaluate the efficacy of commercially available chlorine dioxide (CD) products to reduce viral loads on PPE (face masks) and surfaces using a novel dry gas release intervention. The efficacy of CD slow release 30-day sachets was tested on N95 face masks inoculated with human coronavirus OC43 in suspension. One sachet was placed with …


Association Of Nt-Probnp, Blood Pressure, And Cardiovascular Events: The Aric Study, Aliza Hussain, Wensheng Sun, Anita Deswal, James A De Lemos, John W Mcevoy, Ron C Hoogeveen, Kunihiro Matsushita, David Aguilar, Biykem Bozkurt, Salim S Virani, Amil M Shah, Elizabeth Selvin, Chiadi Ndumule, Christie M Ballantyne, Vijay Nambi Feb 2021

Association Of Nt-Probnp, Blood Pressure, And Cardiovascular Events: The Aric Study, Aliza Hussain, Wensheng Sun, Anita Deswal, James A De Lemos, John W Mcevoy, Ron C Hoogeveen, Kunihiro Matsushita, David Aguilar, Biykem Bozkurt, Salim S Virani, Amil M Shah, Elizabeth Selvin, Chiadi Ndumule, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

BACKGROUND: Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.

OBJECTIVES: This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.

METHODS: Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, …


Hermansky-Pudlak Syndrome-2 Alters Mitochondrial Homeostasis In The Alveolar Epithelium Of The Lung, Karina Cuevas-Mora, Willy Roque, Hoora Shaghaghi, Bernadette R Gochuico, Ivan O Rosas, Ross Summer, Freddy Romero Feb 2021

Hermansky-Pudlak Syndrome-2 Alters Mitochondrial Homeostasis In The Alveolar Epithelium Of The Lung, Karina Cuevas-Mora, Willy Roque, Hoora Shaghaghi, Bernadette R Gochuico, Ivan O Rosas, Ross Summer, Freddy Romero

Faculty, Staff and Students Publications

BACKGROUND: Mitochondrial dysfunction has emerged as an important player in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a common cause of idiopathic interstitial lung disease in adults. Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder that causes a similar type of pulmonary fibrosis in younger adults, although the role of mitochondrial dysfunction in this condition is not understood.

METHODS: We performed a detailed characterization of mitochondrial structure and function in lung tissues and alveolar epithelial cells deficient in the adaptor protein complex 3 beta 1 (Ap3b1) subunit, the gene responsible for causing subtype 2 of HPS (HPS-2).

RESULTS: We …


Efficacy And Safety Of The Mrna-1273 Sars-Cov-2 Vaccine, Lindsey R Baden, Hana M El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, Stephen A Spector, Nadine Rouphael, C Buddy Creech, John Mcgettigan, Shishir Khetan, Nathan Segall, Joel Solis, Adam Brosz, Carlos Fierro, Howard Schwartz, Kathleen Neuzil, Larry Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, John Mascola, Laura Polakowski, Julie Ledgerwood, Barney S Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Han, Melanie Ivarsson, Jacqueline Miller, Tal Zaks, Cove Study Group Feb 2021

Efficacy And Safety Of The Mrna-1273 Sars-Cov-2 Vaccine, Lindsey R Baden, Hana M El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, Stephen A Spector, Nadine Rouphael, C Buddy Creech, John Mcgettigan, Shishir Khetan, Nathan Segall, Joel Solis, Adam Brosz, Carlos Fierro, Howard Schwartz, Kathleen Neuzil, Larry Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, John Mascola, Laura Polakowski, Julie Ledgerwood, Barney S Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Han, Melanie Ivarsson, Jacqueline Miller, Tal Zaks, Cove Study Group

Faculty, Staff and Students Publications

BACKGROUND: Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.

METHODS: This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. …


Ubiquitin Ligation To F-Box Protein Targets By Scf–Rbr E3–E3 Super-Assembly, Daniel Horn-Ghetko, David T. Krist, J. Rajan Prabu, Kheewoong Baek, Monique P.C. Mulder, Maren Klügel, Daniel C. Scott, Huib Ovaa, Gary Kleiger, Brenda A. Schulman Feb 2021

Ubiquitin Ligation To F-Box Protein Targets By Scf–Rbr E3–E3 Super-Assembly, Daniel Horn-Ghetko, David T. Krist, J. Rajan Prabu, Kheewoong Baek, Monique P.C. Mulder, Maren Klügel, Daniel C. Scott, Huib Ovaa, Gary Kleiger, Brenda A. Schulman

Chemistry and Biochemistry Faculty Research

© 2021, The Author(s). E3 ligases are typically classified by hallmark domains such as RING and RBR, which are thought to specify unique catalytic mechanisms of ubiquitin transfer to recruited substrates1,2. However, rather than functioning individually, many neddylated cullin–RING E3 ligases (CRLs) and RBR-type E3 ligases in the ARIH family—which together account for nearly half of all ubiquitin ligases in humans—form E3–E3 super-assemblies3–7. Here, by studying CRLs in the SKP1–CUL1–F-box (SCF) family, we show how neddylated SCF ligases and ARIH1 (an RBR-type E3 ligase) co-evolved to ubiquitylate diverse substrates presented on various F-box proteins. We developed activity-based chemical probes that …


Lkb1 And Ampk Instruct Cone Nuclear Position To Modify Visual Function, Courtney A Burger, Nicholas E Albrecht, Danye Jiang, Justine H Liang, Ross A Poché, Melanie A Samuel Feb 2021

Lkb1 And Ampk Instruct Cone Nuclear Position To Modify Visual Function, Courtney A Burger, Nicholas E Albrecht, Danye Jiang, Justine H Liang, Ross A Poché, Melanie A Samuel

Faculty, Staff and Students Publications

Cone photoreceptors detect light and are responsible for color vision. These cells display a distinct polarized morphology where nuclei are precisely aligned in the apical retina. However, little is known about the mechanisms involved in cone nuclear positioning or the impact of this organization on retina function. We show that the serine/threonine kinase LKB1 and one of its substrates, AMPK, regulate cone nuclear positioning. In the absence of either molecule, cone nuclei are misplaced along the axon, resulting in altered nuclear lamination. LKB1 is required specifically in cones to mediate this process, and disruptions in nuclear alignment result in reduced …


The C. Neoformans Cell Wall: A Scaffold For Virulence, Christine Chrissian Feb 2021

The C. Neoformans Cell Wall: A Scaffold For Virulence, Christine Chrissian

Dissertations, Theses, and Capstone Projects

Cryptococcus neoformans is a globally distributed opportunistic fungal pathogen and the causative agent of life threatening cryptococcal meningoencephalitis in immunocompromised individuals, resulting in ~180,000 deaths each year worldwide. A primary virulence-associated trait of this organism is the production of melanin. Melanins are a class of diverse pigments produced via the oxidation and polymerization of aromatic ring compounds that have a characteristically complex, heterogenous, and amorphous structure. They are synthesized by representatives of all biological kingdoms and share a multitude of remarkable properties such as the ability to absorb ultraviolet (UV) light and protect against ionizing radiation. Melanin production in fungi …


Direct Recruitment Of Eif4gi And/Dap5 To The 5' Utr Of A Subset Of Human Mrna Drives Their Cap-Independent Translation, Solomon A. Haizel Feb 2021

Direct Recruitment Of Eif4gi And/Dap5 To The 5' Utr Of A Subset Of Human Mrna Drives Their Cap-Independent Translation, Solomon A. Haizel

Dissertations, Theses, and Capstone Projects

During unfavorable cellular conditions (e.g., tumor hypoxia, viral infection, nutrient deprivation, etc.), the canonical, cap-dependent translation initiation pathway in human cells is suppressed by sequestration of the cap-binding protein, eukaryotic initiation factor(eIF) 4E, by 4E-binding proteins. Circumvention of cap-dependent translation shutdown has been linked to tumor development and cancer progression. The stress-induced repression of cap-dependent translation has also been correlated with increased eIF4GI and its homolog, Death Associated Protein 5 (DAP5) expression levels, suggesting these factors have a role in cap-independent translation. Despite several evidence pointing towards a link upregulation of eIF4GI and /DAP5 levels during stress conditions, and the …


Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex, Michael Redlich Feb 2021

Third Harmonic Generation: A Method For Visualizing Myelin In The Murine Cerebral Cortex, Michael Redlich

Dissertations, Theses, and Capstone Projects

Here we present the use of Third Harmonic Generation (THG) for the label-free imaging of myelinated axons in the murine cerebral cortex. Myelin plays an important role in the processes of learning and disease. However, much of the myelin biology research thus far has focused on white matter tracts where myelin is more visible. Much is still unknown, particularly with regard to myelin in gray matter. First, we engage in THG microscopy using an optical parametric oscillator pumped by a titanium-sapphire laser to demonstrate the utility of the technique for imaging myelin in vivo. Second, we investigate the use of …


Using The Marcus Inverted Region And Artificial Cofactors To Create A Charge Separated State In De Novo Designed Proteins, Eskil Me Andersen Feb 2021

Using The Marcus Inverted Region And Artificial Cofactors To Create A Charge Separated State In De Novo Designed Proteins, Eskil Me Andersen

Dissertations, Theses, and Capstone Projects

To create an efficient de novo photosynthetic protein it is important to create long lived charge separated states. Achieving stable charge separation leads to an increase in the efficiency of the photosynthetic reaction which in turn leads to higher yields of end products, such as biofuels, electrical charge, or synthetic chemicals. In an attempt to create charge separated states in de novo proteins we hypothesized that we could engineer the free energy gaps in the proteins from excited primary donor (PD) to acceptor (A), and A back to ground state PD such that the forward electron transfer (ET) would be …


Links Between Thrombosis And Inflammation In Traumatic Brain Injury, W Brad Hubbard, Jing-Fei Dong, Miguel A Cruz, Rolando E Rumbaut Feb 2021

Links Between Thrombosis And Inflammation In Traumatic Brain Injury, W Brad Hubbard, Jing-Fei Dong, Miguel A Cruz, Rolando E Rumbaut

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) continues to be a major healthcare problem and there is much to be explored regarding the secondary pathobiology to identify early predictive markers and new therapeutic targets. While documented changes in thrombosis and inflammation in major trauma have been well described, growing evidence suggests that isolated TBI also results in systemic alterations in these mechanisms. Here, we review recent experimental and clinical findings that demonstrate how blood-brain barrier dysfunction, systemic immune response, inflammation, platelet activation, and thrombosis contribute significantly to the pathogenesis of TBI. Despite advances in the links between thrombosis and inflammation, there is a …


Relation Of Magnetic Resonance Imaging Based Arterial Signal Enhancement To Markers Of Peripheral Artery Disease, Olga A Gimnich, Jonathan Holbrook, Tatiana Belousova, Christina M Short, Addison A Taylor, Vijay Nambi, Joel D Morrisett, Christie M Ballantyne, Jean Bismuth, Dipan J Shah, Gerd Brunner Feb 2021

Relation Of Magnetic Resonance Imaging Based Arterial Signal Enhancement To Markers Of Peripheral Artery Disease, Olga A Gimnich, Jonathan Holbrook, Tatiana Belousova, Christina M Short, Addison A Taylor, Vijay Nambi, Joel D Morrisett, Christie M Ballantyne, Jean Bismuth, Dipan J Shah, Gerd Brunner

Faculty, Staff and Students Publications

Peripheral artery disease (PAD) is associated with impaired lower extremity function. We hypothesized that contrast-enhanced magnetic resonance imaging (CE-MRI) based arterial signal enhancement (SE) measures are associated with markers of PAD. A total of 66 participants were enrolled, 10 were excluded due to incomplete data, resulting in 56 participants for the final analyses (36 PAD, 20 matched controls). MR imaging was performed postreactive hyperemia using bilateral thigh blood-pressure cuffs. First pass-perfusion images were acquired at the mid-calf region with a high-resolution saturation recovery gradient echo pulse sequence, and arterial SE was measured for the lower extremity arteries. As expected, peak …


Education Of Infectious Diseases Fellows During The Covid-19 Pandemic Crisis: Challenges And Opportunities, Lisa M Chirch, Wendy S Armstrong, Gayle P Balba, Prathit A Kulkarni, Constance A Benson, Victoria Konold, Vera P Luther, Obinna N Nnedu, Sarah Perloff, Raymund R Razonable, Wendy Stead, George R Thompson, Michael T Melia Feb 2021

Education Of Infectious Diseases Fellows During The Covid-19 Pandemic Crisis: Challenges And Opportunities, Lisa M Chirch, Wendy S Armstrong, Gayle P Balba, Prathit A Kulkarni, Constance A Benson, Victoria Konold, Vera P Luther, Obinna N Nnedu, Sarah Perloff, Raymund R Razonable, Wendy Stead, George R Thompson, Michael T Melia

Faculty, Staff and Students Publications

One of the many challenges that has befallen the Infectious Diseases and Graduate Medical Education communities during the coronavirus disease 2019 (COVID-19) pandemic is the maintenance of continued effective education and training of the future leaders of our field. With the remarkable speed and innovation that has characterized the responses to this pandemic, educators everywhere have adapted existing robust and safe learning environments to meet the needs of our learners. This paper will review distinct aspects of education and training of the Infectious Diseases fellows we believe the COVID-19 pandemic has impacted most, including mentoring, didactics, and wellness. We anticipate …


Calcium Ions Trigger The Exposure Of Phosphatidylserine On The Surface Of Necrotic Cells, Yoshitaka Furuta, Omar Pena-Ramos, Zao Li, Lucia Chiao, Zheng Zhou Feb 2021

Calcium Ions Trigger The Exposure Of Phosphatidylserine On The Surface Of Necrotic Cells, Yoshitaka Furuta, Omar Pena-Ramos, Zao Li, Lucia Chiao, Zheng Zhou

Faculty, Staff and Students Publications

Intracellular Ca2+ level is under strict regulation through calcium channels and storage pools including the endoplasmic reticulum (ER). Mutations in certain ion channel subunits, which cause mis-regulated Ca2+ influx, induce the excitotoxic necrosis of neurons. In the nematode Caenorhabditis elegans, dominant mutations in the DEG/ENaC sodium channel subunit MEC-4 induce six mechanosensory (touch) neurons to undergo excitotoxic necrosis. These necrotic neurons are subsequently engulfed and digested by neighboring hypodermal cells. We previously reported that necrotic touch neurons actively expose phosphatidylserine (PS), an "eat-me" signal, to attract engulfing cells. However, the upstream signal that triggers PS externalization remained elusive. Here we …


The Gut Microbiome Contributes To Blood-Brain Barrier Disruption In Spontaneously Hypertensive Stroke Prone Rats, James W Nelson, Sharon C Phillips, Bhanu P Ganesh, Joseph F Petrosino, David J Durgan, Robert M Bryan Feb 2021

The Gut Microbiome Contributes To Blood-Brain Barrier Disruption In Spontaneously Hypertensive Stroke Prone Rats, James W Nelson, Sharon C Phillips, Bhanu P Ganesh, Joseph F Petrosino, David J Durgan, Robert M Bryan

Faculty, Staff and Students Publications

In recent years, it has become apparent that the gut microbiome can influence the functioning and pathological states of organs and systems throughout the body. In this study, we tested the hypothesis that the gut microbiome has a major role in the disruption of the blood-brain barrier (BBB) in the spontaneously hypertensive stroke prone rats (SHRSP), an animal model for hypertensive cerebral small vessel disease (CSVD). Loss of BBB is thought to be an early and initiating component to the full expression of CSVD in animal models and humans. To test this hypothesis, newly born SHRSP pups were placed with …


Prevalence Of Gastric Intestinal Metaplasia In A Multiethnic Us Veterans Population, Theresa H Nguyen, Mimi C Tan, Yan Liu, Massimo Rugge, Aaron P Thrift, Hashem B El-Serag Feb 2021

Prevalence Of Gastric Intestinal Metaplasia In A Multiethnic Us Veterans Population, Theresa H Nguyen, Mimi C Tan, Yan Liu, Massimo Rugge, Aaron P Thrift, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: There is a need to identify individuals with gastric intestinal metaplasia, a precursor to gastric cancer, so they can be offered screening and surveillance. We examined the prevalence of gastric intestinal metaplasia, detected by upper endoscopy biopsy analysis, in different race and ethnic subgroups. We also investigated the extent to which Helicobacter pylori infection, with or without acute and chronic gastritis, accounts for observed associations between race or ethnicity and risk of gastric intestinal metaplasia.

METHODS: We used data from a cross-sectional study of consecutively recruited patients at the Michael E. DeBakey Veterans Affairs Medical Center in …


Prevalence Of Barrett’S Esophagus And Performance Of Societal Screening Guidelines In An Unreferred Primary Care Population Of Us Veterans, Theresa H Nguyen, Aaron P Thrift, Massimo Rugge, Hashem B El-Serag Feb 2021

Prevalence Of Barrett’S Esophagus And Performance Of Societal Screening Guidelines In An Unreferred Primary Care Population Of Us Veterans, Theresa H Nguyen, Aaron P Thrift, Massimo Rugge, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Less than 10% of patients diagnosed with esophageal adenocarcinoma have a pre-existing Barrett's esophagus (BE) diagnosis, possibly because of suboptimal performance of guidelines. We examined the prevalence of BE in a previously unscreened primary care population and the potential yield of practice BE screening guidelines.

METHODS: This was a retrospective analysis of a prospective cross-sectional study of consecutively recruited unreferred patients from primary care clinics who underwent study upper endoscopy. We examined the performance of BE screening guidelines of the European Society of Gastrointestinal Endoscopy (ESGE), British Society of Gastroenterology (BSG), American Society for Gastrointestinal Endoscopy (ASGE), …


Adherence To The Kidney Disease: Improving Global Outcomes Ckd Guideline In Nephrology Practice Across Countries, Bénédicte Stengel, Daniel Muenz, Charlotte Tu, Elodie Speyer, Natalia Alencar De Pinho, Christian Combe, Kunihiro Yamagata, Helmut Reichel, Danilo Fliser, Ziad A Massy, Antonio A Lopes, Michel Jadoul, Wolfgang C Winkelmayer, Ronald L Pisoni, Bruce M Robinson, Roberto Pecoits-Filho Feb 2021

Adherence To The Kidney Disease: Improving Global Outcomes Ckd Guideline In Nephrology Practice Across Countries, Bénédicte Stengel, Daniel Muenz, Charlotte Tu, Elodie Speyer, Natalia Alencar De Pinho, Christian Combe, Kunihiro Yamagata, Helmut Reichel, Danilo Fliser, Ziad A Massy, Antonio A Lopes, Michel Jadoul, Wolfgang C Winkelmayer, Ronald L Pisoni, Bruce M Robinson, Roberto Pecoits-Filho

Faculty, Staff and Students Publications

INTRODUCTION: The uptake of the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 chronic kidney disease (CKD) Guideline is not fully described in real-world nephrology practice across the world.

METHODS: We used baseline data from the CKD Outcomes and Practice Patterns Study (2013-2017), a 4-country cohort of patients with estimated glomerular filtration rate/min per 1.73 m

RESULTS: The mean age ranged from 65 years in Brazil to 72 years in Germany. Albuminuria (mostly proteinuria) was measured routinely in 36% to 43% of patients in Brazil, Germany, and the United States. Blood pressure control (≤140/90 mm Hg) ranged from 49% in France …


Effects Of Cocaine And/Or Heroin Use On Resting Cardiovascular Function, Shabber Syed Bs, Lina A. Shkokani Bs, Leslie H. Lundahl Phd, Renato S. Roxas Md, Philip D. Levy Md, Mark K. Greenwald Phd Jan 2021

Effects Of Cocaine And/Or Heroin Use On Resting Cardiovascular Function, Shabber Syed Bs, Lina A. Shkokani Bs, Leslie H. Lundahl Phd, Renato S. Roxas Md, Philip D. Levy Md, Mark K. Greenwald Phd

Medical Student Research Symposium

Background: Regular cocaine and/or heroin use is associated with major health risks, especially cardiovascular disease (CVD), but confounded by other factors.

Objectives: We examined effects of chronic (years of regular use) and recent (past-month) use of cocaine and heroin, controlling for other factors, on resting cardiovascular function.

Methods: In a sample of cocaine and/or heroin users (N=292), we obtained data on demographics, body mass index (BMI), history of substance use, and electrocardiogram, heart rate (HR) and blood pressure (BP). Following bivariate correlations, three-block (1: demographics, BMI; 2: tobacco, alcohol, marijuana; 3: cocaine, heroin) regression analyses were …


Regional N-Glycan And Lipid Analysis From Tissues Using Maldi-Mass Spectrometry Imaging, Alexandra E. Stanback, Lindsey R. Conroy, Lyndsay E. A. Young, Tara R. Hawkinson, Kia H. Markussen, Harrison A. Clarke, Derek B. Allison, Ramon C. Sun Jan 2021

Regional N-Glycan And Lipid Analysis From Tissues Using Maldi-Mass Spectrometry Imaging, Alexandra E. Stanback, Lindsey R. Conroy, Lyndsay E. A. Young, Tara R. Hawkinson, Kia H. Markussen, Harrison A. Clarke, Derek B. Allison, Ramon C. Sun

Neuroscience Faculty Publications

N-glycans and lipids are structural metabolites that play important roles in cellular processes. Both show unique regional distribution in tissues; therefore, spatial analyses of these metabolites are crucial to our understanding of cellular physiology. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is an innovative technique that enables in situ detection of analytes with spatial distribution. This workflow details a MALDI-MSI protocol for the spatial profiling of N-glycans and lipids from tissues following application of enzyme and MALDI matrix.

For complete details on the use and execution of this protocol, please refer to Drake et al. (2018) and Andres et al. (2020).


Generating Pennycress (Thlaspi Arvense) Seed Triacylglycerols And Acetyl-Triacylglycerols Containing Medium-Chain Fatty Acids, Maliheh Esfahanian, Tara J. Nazarenus, Meghan M. Freund, Gary Mcintosh, Winthrop B. Phippen, Mary E. Phippen, Timothy P. Durrett, Edgar B. Cahoon, John C. Sedbrook Jan 2021

Generating Pennycress (Thlaspi Arvense) Seed Triacylglycerols And Acetyl-Triacylglycerols Containing Medium-Chain Fatty Acids, Maliheh Esfahanian, Tara J. Nazarenus, Meghan M. Freund, Gary Mcintosh, Winthrop B. Phippen, Mary E. Phippen, Timothy P. Durrett, Edgar B. Cahoon, John C. Sedbrook

Department of Biochemistry: Faculty Publications

Thlaspi arvense L. (pennycress) is a cold-tolerant Brassicaceae that produces large amounts of seeds rich in triacylglycerols and protein, making it an attractive target for domestication into an offseason oilseed cash cover crop. Pennycress is easily genetically transformed, enabling synthetic biology approaches to tailor oil properties for specific biofuel and industrial applications. To test the feasibility in pennycress of producing TAGs and acetyl-TAGs rich in medium-chain fatty acids (MCFAs; C6–C14) for industrial, biojet fuel and improved biodiesel applications, we generated transgenic lines with seed-specific expression of unique acyltransferase (LPAT and diacylglycerol acyltransferase) genes and thioesterase (FatB) genes isolated from Cuphea …


Transcriptional Coupling And Repair Of 8-Oxog Activate A Reca-Dependent Checkpoint That Controls The Onset Of Sporulation In Bacillus Subtilis, Valeria P. Suárez, Lissett E. Martínez, Hilda C. Leyva-Sánchez, Luz I. Valenzuela-García, Reyna Lara-Martínez, Luis F. Jiménez-García, Norma Ramírez-Ramírez, Armando Obregon-Herrera, Mayra Cuéllar-Cruz, Eduardo A. Robleto, Mario Pedraza-Reyes Jan 2021

Transcriptional Coupling And Repair Of 8-Oxog Activate A Reca-Dependent Checkpoint That Controls The Onset Of Sporulation In Bacillus Subtilis, Valeria P. Suárez, Lissett E. Martínez, Hilda C. Leyva-Sánchez, Luz I. Valenzuela-García, Reyna Lara-Martínez, Luis F. Jiménez-García, Norma Ramírez-Ramírez, Armando Obregon-Herrera, Mayra Cuéllar-Cruz, Eduardo A. Robleto, Mario Pedraza-Reyes

Life Sciences Faculty Research

© 2021, The Author(s). During sporulation Bacillus subtilis Mfd couples transcription to nucleotide excision repair (NER) to eliminate DNA distorting lesions. Here, we report a significant decline in sporulation following Mfd disruption, which was manifested in the absence of external DNA-damage suggesting that spontaneous lesions activate the function of Mfd for an efficient sporogenesis. Accordingly, a dramatic decline in sporulation efficiency took place in a B. subtilis strain lacking Mfd and the repair/prevention guanine oxidized (GO) system (hereafter, the ∆GO system), composed by YtkD, MutM and MutY. Furthermore, the simultaneous absence of Mfd and the GO system, (i) sensitized sporulating …


Inhibition Of Matrix Metalloproteinase-9 Secretion By Dimethyl Sulfoxide And Cyclic Adenosine Monophosphate In Human Monocytes, Darcy Denner, Maria Udan-Johns, Michael Nichols Jan 2021

Inhibition Of Matrix Metalloproteinase-9 Secretion By Dimethyl Sulfoxide And Cyclic Adenosine Monophosphate In Human Monocytes, Darcy Denner, Maria Udan-Johns, Michael Nichols

Chemistry & Biochemistry Faculty Works

BACKGROUND Matrix metalloproteinases (MMPs), including MMP-9, are an integral part of the immune response and are upregulated in response to a variety of stimuli. New details continue to emerge concerning the mechanistic and regulatory pathways that mediate MMP-9 secretion. There is significant evidence for regulation of inflammation by dimethyl sulfoxide (DMSO) and 3',5'-cyclic adenosine monophosphate (cAMP), thus investigation of how these two molecules may regulate both MMP-9 and tumor necrosis factor α (TNFα) secretion by human monocytes was of high interest. The hypothesis tested in this study was that DMSO and cAMP regulate MMP-9 and TNFα secretion by distinct mechanisms. …


The Effect Of Alcalase Concentration On The Proteins From The Shells Of Litopenaeus Setiferus (White Shrimp), Liam T. Quan Jan 2021

The Effect Of Alcalase Concentration On The Proteins From The Shells Of Litopenaeus Setiferus (White Shrimp), Liam T. Quan

Journal of the South Carolina Academy of Science

Chitin is a naturally abundant polymer that also happens to be biodegradable. Chitin can be used in a variety of different products such as biodegradable plastics, papers, medical products, foods, and medical treatments. To extract chitin, shells must be demineralized and deproteinized. The goal of this experiment was to examine the effect of the protease Alcalase in the deproteinization of litopenaeus setiferus shells. The hypothesis was that if the concentration of Alcalase increased, then the absorbance of proteins in the spectrophotometer reading would increase. The null hypothesis was that if the concentration increased there would be no change in absorption. …