Cells Commons^™

Moerv14 Mediates The Intracellular Transport Of Cell Membrane Receptors To Govern The Appressorial Formation And Pathogenicity Of Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Graduate Studies Faculty Publications

Magnaporthe oryzae causes rice blasts posing serious threats to food security worldwide. During infection, M. oryzae utilizes several transmembrane receptor proteins that sense cell surface cues to induce highly specialized infectious structures called appressoria. However, little is known about the mechanisms of intracellular receptor tracking and their function. Here, we described that disrupting the coat protein complex II (COPII) cargo protein MoErv14 severely affects appressorium formation and pathogenicity as the ΔMoerv14 mutant is defective not only in cAMP production but also in the phosphorylation of the mitogen-activated protein kinase (MAPK) MoPmk1. Studies also showed that either externally supplementing cAMP or …

Triazole Compounds – Potentials In The Treatment Of Cystic Fibrosis, Maggie Taylor

Undergraduate Research Conference

Cystic Fibrosis (CF) is a genetic disease that affects the respiratory and digestive system and is most common among Caucasians of Northern European origin. CF is caused by mutations in a membrane protein CFTR (Cystic Fibrosis Transmembrane-conductance Regulator). This mutation impairs the membrane protein’s chloride ion channel function. One of the most common CFTR mutations is the DF508 mutation that affects over 70% of CF cases. Our research has shown that the DF508-CFTR mutation can be partially reversed by physical and chemical means [Heda & Marino, BBRC, 271:659-664, 2000]. In cell lines expressing DF508-CFTR, synthetic anion carriers have shown to …

Enhanced Ca2+-Channeling Complex Formation At The Er-Mitochondria Interface Underlies The Pathogenesis Of Alcohol-Associated Liver Disease, Themis Thoudam, Dipanjan Chanda, Jung Yi Lee, Min Kyo Jung, Ibotombi Singh Sinam, Byung Gyu Kim, Bo Yoon Park, Woong Hee Kwon, Hyo Jeong Kim, Myeongjin Kim, Chae Won Lim, Hoyul Lee, Yang Hoon Huh, Caroline A. Miller, Romil Saxena, Nicholas J. Skill, Nazmul Huda, Praveen Kusumanchi, Jing Ma, Zhihong Yang, Min Ji Kim, Ji Young Mun, Robert A. Harris, Jae Han Jeon, Suthat Liangpunsakul, In Kyu Lee

School of Medicine Faculty Publications

Ca2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation in ALD remain elusive. Here, we demonstrate that an aberrant increase in hepatic GRP75-mediated mitochondria-associated ER membrane (MAM) Ca2+-channeling (MCC) complex formation promotes mitochondrial dysfunction in vitro and in male mouse model of ALD. Unbiased transcriptomic analysis reveals PDK4 as a prominently inducible MAM kinase in ALD. Analysis of human ALD cohorts further corroborate these findings. Additional mass spectrometry analysis unveils GRP75 as a downstream phosphorylation target of PDK4. Conversely, non-phosphorylatable GRP75 …

Lipoprotein(A) In Atherosclerotic Cardiovascular Disease And Aortic Stenosis: A European Atherosclerosis Society Consensus Statement, Florian Kronenberg, Samia Mora, Erik S G Stroes, Brian Ference Ference Ference, Benoit J. Arsenault, Lars Berglund, Marc R. Dweck, Marlys Koschinsky, Gilles Lambert, Salim S. Virani

Office of the Provost

This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do …

H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …

Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang

School of Public Health Faculty Publications

Quitting smoking could potentially minimize the risk of a high neutrophil-to-lymphocyte ratio (NLR) among tobacco use-related (TUR) cancer survivors. A total of 1263 TUR cancer survivors aged 20 to 85 years old were investigated using data from the National Health and Nutritional Examination Survey 1999-2018. The primary outcome was the NLR, which was defined as having two levels: high-risk (≥ 3) and low-risk (< 3). The association between smoking cessation time and a high-risk NLR level was analyzed using weighted logistic regression models. Overall, the current smoking rate of TUR cancer survivors was found to be 21.7%. Older age (75 years above), gender and respiratory-related cancers are covariables associated with high risk of NLR levels for individual who identified as Non-Hispanic White (NHW). Non-Hispanic Black (NHB) (n = 27) who quit smoking after a cancer diagnosis were associated with the highest risk of a high NLR (OR 4.83, 95% CI 1.40-16.61, p = 0.01) compared to NHB nonsmokers (n = 139). These findings suggest that the risk of a high NLR level is strongly associated with the time of smoking cessation in NHB TUR cancer survivors. As a result, NHB TUR cancer survivors should quit smoking as soon as possible because the benefits of quitting smoking were observed over the 5 year period following smoking cessation.

Frequency Of Von Willebrand Disease And Its Types: Data From A Tertiary Care Hospital Of Karachi, Pakistan, Jyoti Mohan Lal, Anila Rashid, Natasha Ali

Department of Pathology and Laboratory Medicine

Introduction: von Willebrand disease is the most common inherited bleeding disorder. It is classified into 3 main types, type I and III are quantitative defects whereas type II is qualitative defect which is further sub-classified in to II-A, II-B, II-M, II-N. The aim of the present study is to see frequency and types of von Willebrand disease in a tertiary care hospital of Karachi, Pakistan.
Materials and methods: This retrospective cross-sectional study was conducted in the section of Hematology and Transfusion Medicine, Department of Pathology and Laboratory Medicine, the Aga Khan University hospital, Karachi, from May 2020 to April 2021 …

Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava

School of Medicine Faculty Publications

Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial–mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with …

Relationship Of Abdominal Circumference And Trunk Length With Spinal Anesthesia Block Height In Geriatric Patients Undergoing Transurethral Resection Of Prostate, Muhammad Yahya, Aliya Ahmed, Iayla Fatima, Muhammad Nasir

Department of Anaesthesia

Introduction: Spinal anesthesia is commonly used for various surgical procedures. Prediction of spinal anesthesia block height is always a challenging task for anesthetists. Higher than desired levels of spinal anesthesia blocks are associated with serious side effects, while inadequate block height does not provide satisfactory surgical anesthesia. In this study, we observed the relationship between the ratio of trunk length (TL) and square of the abdominal circumference (AC²) and spinal anesthesia sensory block height in geriatric patients undergoing transurethral resection of the prostate (TURP).
Material & Methods: This is a cross-sectional study conducted at the Aga Khan University …

Testicular Choriocarcinoma With Small Bowel Metastasis And Active Gastrointestinal Bleeding, Asad Saulat Fatimi, Khizer Masroor Anns, Faheemullah Khan, Wasim Ahmed Memon, Junaid Iqbal, Muhammad Aman, Izaz Ahmad, Sahar Fatima

Medical College Documents

Testicular choriocarcinomas make up less than 1% of all germ-cell tumors and are highly malignant, attributable to hematogenous spread. While the most common sites of metastasis are the lungs and liver, metastatic spread to the gastrointestinal tract is rare wherein patients may present with GI distress or even an upper GI bleed. In this report, we present a case of known testicular choriocarcinoma in a 40-year-old male who presented to the emergency room with severe anemia and a suspected upper GI bleed.

Pulsed Electric Field Ablation Of Esophageal Malignancies And Mitigating Damage To Smooth Muscle: An In Vitro Study, Emily Gudvangen, Uma Mangalanathan, Iurii Semenov, Allen S. Kiester, Mark A. Keppler, Bennett L. Ibey, Joel N. Bixler, Andrei G. Pakhomov

Bioelectrics Publications

Cancer ablation therapies aim to be efficient while minimizing damage to healthy tissues. Nanosecond pulsed electric field (nsPEF) is a promising ablation modality because of its selectivity against certain cell types and reduced neuromuscular effects. We compared cell killing efficiency by PEF (100 pulses, 200 ns–10 µs duration, 10 Hz) in a panel of human esophageal cells (normal and pre-malignant epithelial and smooth muscle). Normal epithelial cells were less sensitive than the pre-malignant ones to unipolar PEF (15–20% higher LD50, p < 0.05). Smooth muscle cells (SMC) oriented randomly in the electric field were more sensitive, with 30–40% lower LD50 (p < 0.01). Trains of ten, 300-ns pulses at 10 kV/cm caused twofold weaker electroporative uptake of YO-PRO-1 dye in normal epithelial cells than in either pre-malignant cells or in SMC oriented perpendicularly to the field. Aligning SMC with the field reduced the dye uptake fourfold, along with a twofold reduction in Ca²⁺ transients. A 300-ns pulse induced a twofold smaller transmembrane potential in cells aligned with the field, making them …

Interactions Of Carboxylated Nanodiamonds With Mouse Macrophages Cell Line And Primary Cells, Maisoun Bani-Hani, Stephen J. Beebe, Michael W. Stacey, Christopher Osgood

Bioelectrics Publications

Nanodiamonds (ND) have attracted significant interest for their use in several biomedical applications. These applications can be very useful if the safety and compatibility of ND are proven. We assessed the effects of ND (100 nm, Carboxylated) on primary macrophages and a macrophage-like cell line and found that these particles are not toxic to these cells at lower concentrations but may interfere with cell functions and differentiation. Internalization of ND by these cells in a time- and dose-dependent manner was mostly via phagocytosis and clathrin-dependent endocytosis and localized to the cytoplasm but not into the nucleus. No significant induction of …

Gene Expression Under Combined Hypoxia And Acidosis In Chondrosarcoma, Michael Stacey, Kostika Vangjeli, Christopher Osgood

Bioelectrics Publications

Chondrosarcomas are the second most common cause of bone cancer and are removed surgically with wide margins. On recurrence, they are resistant to chemo and radiation therapy and new treatment options are critically required. This tumor type produces hyaline cartilage, a cartilage normally formed under hypoxic and acidic environment due to lack of vasculature in cartilage. Paradoxically, chondrosarcomas arise in the well vascularized, oxygen rich environment of the bone. Hypoxia and acidosis are two stressors where the cellular effects are typically reported separately even though cells experience combined effects of hypoxia and acidosis. Given the mechanistic links between hypoxia and …

Identification Of Proteins Involved In Cell Membrane Permeabilization By Nanosecond Electric Pulses (Nsep), Giedre Silkuniene, Uma Mangalanathan, Alessandra Rossi, Peter A. Mollica, Andrei G. Pakhomov, Olga N. Pakhomova

Bioelectrics Publications

The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in the cell membrane disrupted by nsEP (20 or 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs) of 316 genes encoding for membrane proteins in U937 human monocytes stably expressing Cas9 nuclease. The extent of membrane permeabilization by nsEP was measured by the uptake of Yo-Pro-1 (YP) dye and compared to sham-exposed KOs and control cells transduced with a non-targeting (scrambled) gRNA. Only two KOs, for SCNN1A and CLCA1 genes, showed a statistically significant reduction in …

Combined 3d Bioprinting And Tissue-Specific Ecm System Reveals The Influence Of Brain Matrix On Stem Cell Differentiation, Martina Zamponi, Peter A. Mollica, Yara Khodour, Julie S. Bjerring, Robert D. Bruno, Patrick C. Sachs

Medical Diagnostics & Translational Sciences Faculty Publications

We have previously shown that human and murine breast extracellular matrix (ECM) can significantly impact cellular behavior, including stem cell fate determination. It has been established that tissue-specific extracellular matrix from the central nervous system has the capacity to support neuronal survival. However, the characterization of its influence on stem cell differentiation and its adaptation to robust 3D culture models is underdeveloped. To address these issues, we combined our 3D bioprinter with hydrogels containing porcine brain extracellular matrix (BMX) to test the influence of the extracellular matrix on stem cell differentiation. Our 3D bioprinting system generated reproducible 3D neural structures …

Ultra-Low Intensity Post-Pulse Affects Cellular Responses Caused By Nanosecond Pulsed Electric Fields, Kamal Asadipour, Carol Zhou, Vincent Yi, Stephen J. Beebe, Shu Xiao

Electrical & Computer Engineering Faculty Publications

High-intensity nanosecond pulse electric fields (nsPEF) can preferentially induce various effects, most notably regulated cell death and tumor elimination. These effects have almost exclusively been shown to be associated with nsPEF waveforms defined by pulse duration, rise time, amplitude (electric field), and pulse number. Other factors, such as low-intensity post-pulse waveform, have been completely overlooked. In this study, we show that post-pulse waveforms can alter the cell responses produced by the primary pulse waveform and can even elicit unique cellular responses, despite the primary pulse waveform being nearly identical. We employed two commonly used pulse generator designs, namely the Blumlein …

Expansion On The Use Of The Novel Compound, Elp-004, Using A Mycobacterium Tuberculosis Experimentation Model, Kendyl Marie Berry

Graduate Theses, Dissertations, and Problem Reports

Osteoarticular tuberculosis (OAT) is a bone degenerative disease that results in bone erosion, joint effusion, joint swelling, and sometimes, nerve compression. OAT occurs from the hematogenous dissemination of Mycobacterium tuberculosis (Mtb) bacilli spreading from the primary site of infection to the bones and joints; the primary site of infection tends to be the lungs as pulmonary tuberculosis infections are the most common. OAT can occur as the result of an active or latent infection. Latent infections result in OAT when bacilli are able to escape granulomas. The incidence of OAT is not as high as pulmonary infections, making up about …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Ptsd And Alcohol Use Disorders Predict The Pace Of Cellular Aging, Sage E. Hawn, Xiang Zhao, Mark W. Miller, Sara Wallander, Christine Govan, Anjanette Stone, Steven A. Schichman, Mark W. Logue, Erika J. Wolf

Psychology Faculty Publications

Advanced epigenetic age is associated with psychopathology and may help to explain the link between psychopathology and physical health morbidity and mortality. Using a longitudinal sample of 171 trauma-exposed Veterans, we modeled the rate of change in epigenetic age across two time points (averaging 5.58 years apart) using two epigenetic age algorithms (GrimAge and Horvath) and tested associations with posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), and depression. Results showed that PTSD (β = .199) and AUD (β = .186) were associated with a quickened pace of epigenetic aging over time (ps < .021). Results replicate and extend prior work and offer foundational support for identifying interventions that slow the pace of biological aging among those with psychopathology.

Cellbrf: A Feature Selection Method For Single-Cell Clustering Using Cell Balance And Random Forest, Yunpei Xu, Hong-Dong Li, Cui-Xiang Lin, Ruiqing Zheng, Yaohang Li, Jinhui Xu, Jianxin Wang

Computer Science Faculty Publications

Motivation

Single-cell RNA sequencing (scRNA-seq) offers a powerful tool to dissect the complexity of biological tissues through cell sub-population identification in combination with clustering approaches. Feature selection is a critical step for improving the accuracy and interpretability of single-cell clustering. Existing feature selection methods underutilize the discriminatory potential of genes across distinct cell types. We hypothesize that incorporating such information could further boost the performance of single cell clustering. Results

We develop CellBRF, a feature selection method that considers genes’ relevance to cell types for single-cell clustering. The key idea is to identify genes that are most important for discriminating …