Digital Commons Network^™

Using Long-Read Cage Sequencing To Profile Cryptic-Promoter-Derived Transcripts And Their Contribution To The Immunopeptidome, Ju Heon Maeng, H Josh Jang, Alan Y Du, Shin-Cheng Tzeng, Ting Wang

2020-Current year OA Pubs

Recent studies have shown that the noncoding genome can produce unannotated proteins as antigens that induce immune response. One major source of this activity is the aberrant epigenetic reactivation of transposable elements (TEs). In tumors, TEs often provide cryptic or alternate promoters, which can generate transcripts that encode tumor-specific unannotated proteins. Thus, TE-derived transcripts (TE transcripts) have the potential to produce tumor-specific, but recurrent, antigens shared among many tumors. Identification of TE-derived tumor antigens holds the promise to improve cancer immunotherapy approaches; however, current genomics and computational tools are not optimized for their detection. Here we combined CAGE technology with …

Single-Pulse Electrical Stimulation Artifact Removal Using The Novel Matching Pursuit-Based Artifact Reconstruction And Removal Method (Mparrm), Tao Xie, Thomas J Foutz, Markus Adamek, James R Swift, Cory S Inman, Joseph R Manns, Eric C Leuthardt, Jon T Willie, Peter Brunner

2020-Current year OA Pubs

No abstract provided.

Genomic Loci Influence Patterns Of Structural Covariance In The Human Brain, Junhao Wen, Aristeidis Sotiras, Daniel S Marcus, Pamela Lamontagne, John C Morris, Et Al.

2020-Current year OA Pubs

Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and …

A Distinct Human Cell Type Expressing Mhcii And Rorγt With Dual Characteristics Of Dendritic Cells And Type 3 Innate Lymphoid Cells, Alina Ulezko Antonova, Changxu Fan, Natalia Jaeger, Patrick Fernandes Rodrigues, Simone Brioschi, Tihana Trsan, José L Fachi, Khai M Nguyen, Ryan M Nunley, Ting Wang, Marina Cella, William Vermi, Marco Colonna, Et Al.

2020-Current year OA Pubs

Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). RORγt

A Distinct Human Cell Type Expressing Mhcii And Rorγt With Dual Characteristics Of Dendritic Cells And Type 3 Innate Lymphoid Cells, Alina Ulezko Antonova, Silvia Lonardi, Matilde Monti, Francesco Missale, Changxu Fan, Matthew L Coates, Mattia Bugatti, Natalia Jaeger, Patrick Fernandes Rodrigues, Simone Brioschi, Tihana Trsan, José L Fachi, Khai M Nguyen, Ryan M Nunley, Daniele Moratto, Stefania Zini, Lingjia Kong, Jacques Deguine, Mark E Peeples, Ramnik J Xavier, Menna R Clatworthy, Ting Wang, Marina Cella, William Vermi, Marco Colonna

The Brown Foundation: Institute of Molecular Medicine

Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). RORγt+ MHCII+ type 3 innate lymphoid cells (ILC3) have also been implicated in the instruction of microbiota-specific Tregs. While RORγt+ APCs have been actively investigated in mice, the identity and function of these cell subsets in humans remain elusive. …

Stabilizing Vimentin Phosphorylation Inhibits Stem-Like Cell Properties And Metastasis Of Hybrid Epithelial/Mesenchymal Carcinomas, Nick A Kuburich, Petra Den Hollander, Maria Castaneda, Mika Pietilä, Ximing Tang, Harsh Batra, Francisco Martínez-Peña, Tanvi H Visal, Tieling Zhou, Breanna R Demestichas, Ritesh V Dontula, Jojo Y Liu, Joanna Joyce Maddela, Reethi S Padmanabhan, Lan Thi Hanh Phi, Matthew J Rosolen, Thiru Sabapathy, Dhiraj Kumar, Filippo G Giancotti, Luke L Lairson, Maria Gabriela Raso, Rama Soundararajan, Sendurai A Mani

Faculty, Staff and Student Publications

Epithelial-mesenchymal transition (EMT) empowers epithelial cells with mesenchymal and stem-like attributes, facilitating metastasis, a leading cause of cancer-related mortality. Hybrid epithelial-mesenchymal (E/M) cells, retaining both epithelial and mesenchymal traits, exhibit heightened metastatic potential and stemness. The mesenchymal intermediate filament, vimentin, is upregulated during EMT, enhancing the resilience and invasiveness of carcinoma cells. The phosphorylation of vimentin is critical to its structure and function. Here, we identify that stabilizing vimentin phosphorylation at serine 56 induces multinucleation, specifically in hybrid E/M cells with stemness properties but not epithelial or mesenchymal cells. Cancer stem-like cells are especially susceptible to vimentin-induced multinucleation relative to …

Microcalcification Crystallography As A Potential Marker Of Dcis Recurrence, Zoey A Miller, Arielle Mueller, Taebeom Kim, Jennifer F Jolivert, Ray Z Ma, Sahil Muthuswami, April Park, Derek B Mcmahon, Kevin T Nead, Ryan M Carey, Robert J Lee

Faculty, Staff and Student Publications

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs, and T2R activation can induce apoptosis. Lidocaine is a local anesthetic that also activates bitter taste receptor 14 (T2R14). Lidocaine has some anti-cancer effects, but the mechanisms are unclear. Here, we find that lidocaine causes intracellular Ca

Lidocaine Induces Apoptosis In Head And Neck Squamous Cell Carcinoma Through Activation Of Bitter Taste Receptor T2r14, Zoey A Miller, Arielle Mueller, Taebeom Kim, Jennifer F Jolivert, Ray Z Ma, Sahil Muthuswami, April Park, Derek B Mcmahon, Kevin T Nead, Ryan M Carey, Robert J Lee

Faculty, Staff and Student Publications

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs, and T2R activation can induce apoptosis. Lidocaine is a local anesthetic that also activates bitter taste receptor 14 (T2R14). Lidocaine has some anti-cancer effects, but the mechanisms are unclear. Here, we find that lidocaine causes intracellular Ca

The Function Of Ask1 In Sepsis And Stress-Induced Disorders, John Kostyak, Steven Mckenzie, Ulhas Naik

Cardeza Foundation for Hematologic Research

Apoptosis signal-regulating kinase 1 (ASK1) is a serine-threonine kinase that is ubiquitously expressed in nucleated cells and is responsible for the activation of multiple mitogen-activated protein kinases (MAPK) to regulate cell stress. Activation of ASK1 via cellular stress leads to activation of downstream signaling components, activation of transcription factors, and proinflammatory cytokine production. ASK1 is also expressed in anucleate platelets and is a key player in platelet activation as it is important for signaling. Interestingly, the mechanism of ASK1 activation is cell type-dependent. In this review we will explore how ASK1 regulates a variety of cellular processes from innate immune …

Pivotal Trial Of A Deep-Learning-Based Retinal Biomarker (Reti-Cvd) In The Prediction Of Cardiovascular Disease: Data From Cmerc-Hi, Chan Joo Lee, Tyler Hyungtaek Rim, Hyun Goo Kang, Joseph Keunhong Yi, Geunyoung Lee, Marco Yu, Soo-Hyun Park, Jin-Taek Hwang, Yih-Chung Tham, Tien Yin Wong, Ching-Yu Cheng, Dong Wook Kim, Sung Soo Kim, Sungha Park

The Brown Foundation: Institute of Molecular Medicine

Objective: The potential of using retinal images as a biomarker of cardiovascular disease (CVD) risk has gained significant attention, but regulatory approval of such artificial intelligence (AI) algorithms is lacking. In this regulated pivotal trial, we validated the efficacy of Reti-CVD, an AI-Software as a Medical Device (AI-SaMD), that utilizes retinal images to stratify CVD risk.

Materials and methods: In this retrospective study, we used data from the Cardiovascular and Metabolic Diseases Etiology Research Center-High Risk (CMERC-HI) Cohort. Cox proportional hazard model was used to estimate hazard ratio (HR) trend across the 3-tier CVD risk groups (low-, moderate-, and high-risk) …

Simvastatin In Critically Ill Patients With Covid-19, Thomas E Hills, Elizabeth Lorenzi, Lindsay R Berry, Murali Shyamsundar, Farah Al-Beidh, Djillali Annane, Yaseen Arabi, Diptesh Aryal, Carly Au, Abigail Beane, Zahra Bhimani, Marc Bonten, Charlotte A Bradbury, Frank M Brunkhorst, Aidan Burrell, Meredith Buxton, Carolyn S Calfee, Maurizio Cecconi, Allen C Cheng, Matthew E Cove, Michelle A Detry, Lise J Estcourt, Mark Fitzgerald, Ewan C Goligher, Herman Goossens, Cameron Green, Rashan Haniffa, David A Harrison, Madiha Hashmi, Alisa M Higgins, Christopher Horvat, David T Huang, Nao Ichihara, Deva Jayakumar, Peter S Kruger, François Lamontagne, Lamprini Lampro, Patrick R Lawler, John C Marshall, Alexina J Mason, Anna Mcglothlin, Shay Mcguinness, Zoe K Mcquilten, Bryan J Mcverry, Paul R Mouncey, Srinivas Murthy, Matthew D Neal, Alistair D Nichol, Cecilia M O'Kane, Rachael L Parke, Jane C Parker, Ebenezer Rabindrarajan, Luis F Reyes, Kathryn M Rowan, Hiroki Saito, Marlene Santos, Christina T Saunders, Christopher W Seymour, Manu Shankar-Hari, Pratik Sinha, B Taylor Thompson, Alexis F Turgeon, Anne M Turner, Frank Van De Veerdonk, Sebastian Weis, Ian S Young, Ryan Zarychanski, Roger J Lewis, Colin J Mcarthur, Derek C Angus, Scott M Berry, Lennie P G Derde, Steve A Webb, Anthony C Gordon, Daniel F Mcauley

Faculty, Staff and Student Publications

BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.

METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical …

Leptin Decreases Gluconeogenesis And Gluconeogenic Substrate Availability In Patients With Lipodystrophy, Emmanuel Quaye, Shaji Chacko, Megan Startzell, Rebecca J Brown

Children’s Nutrition Research Center Staff Publications

Context: The effects of leptin, an adipocyte-derived hormone that signals overall energy sufficiency, can only be studied in leptin-deficient conditions. In patients with lipodystrophy, a rare disease and unique model of leptin deficiency, treatment with recombinant leptin (metreleptin) improves glycemia and decreases energy expenditure. We hypothesized that these improvements might be mediated by reduced gluconeogenesis (GNG), an energy-requiring process.

Objective: To determine the effects of metreleptin on GNG and GNG substrates.

Methods: This was a single-arm prospective study of metreleptin administration in 15 patients with lipodystrophy, 9 of whom had data on GNG (NIH, 2013-2018). We analyzed total GNG, insulin-mediated …

Immunosequencing Applications In Cutaneous T-Cell Lymphoma, Jenna Mandel, Laura Gleason, Daniel Joffe, Safiyyah Bhatti, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Immunosequencing has emerged as a newer clinical test for assessment of T-cell clonality in the blood and skin of cutaneous T-cell lymphoma (CTCL) patients. Utilization of immunosequencing, also known as high-throughput sequencing of the T-cell receptor (HTS-TCR), enables identification and quantification of the precise genetic signature of dominant T-cell clones. Although immunosequencing is more sensitive than commonly used methods such as polymerase chain reaction (PCR) paired with capillary electrophoresis or flow cytometry, it remains underutilized for CTCL management. Nonetheless, incorporation of HTS-TCR in clinical practice offers distinct advantages compared to other molecular analyses that may improve diagnostic evaluation, prognostication, and …

The Involvement Of Hepatic Cytochrome P450s In The Cytotoxicity Of Lapatinib, Si Chen, Xilin Li, Yuxi Li, Xiaobo He, Matthew Bryant, Xuan Qin, Feng Li, Ji-Eun Seo, Xiaoqing Guo, Nan Mei, Lei Guo

Faculty, Staff and Students Publications

Lapatinib, an oral tyrosine kinase inhibitor used as a first-line treatment for HER2-positive breast cancer, has been reported to be associated with hepatotoxicity; however, the underlying mechanisms remain unclear. In this study, we report that lapatinib causes cytotoxicity in multiple types of hepatic cells, including primary human hepatocytes, HepaRG cells, and HepG2 cells. A 24-h treatment with lapatinib induced cell cycle disturbances, apoptosis, and DNA damage, and decreased the protein levels of topoisomerase in HepG2 cells. We investigated the role of cytochrome P450 (CYP)-mediated metabolism in lapatinib-induced cytotoxicity using our previously established HepG2 cell lines, which express each of 14 …

Distinct Gene Expression Signatures Comparing Latent Tuberculosis Infection With Different Routes Of Bacillus Calmette-Guérin Vaccination, Richard F Silver, Mei Xia, Chad E Storer, Jessica R Jarvela, Michelle C Moyer, Azra Blazevic, David A Stoeckel, Erin K Rakey, Jan M Tennant, Johannes B Goll, Richard D Head, Daniel F Hoft

2020-Current year OA Pubs

Tuberculosis remains an international health threat partly because of limited protection from pulmonary tuberculosis provided by standard intradermal vaccination with Bacillus of Calmette and Guérin (BCG); this may reflect the inability of intradermal vaccination to optimally induce pulmonary immunity. In contrast, respiratory Mycobacterium tuberculosis infection usually results in the immune-mediated bacillary containment of latent tuberculosis infection (LTBI). Here we present RNA-Seq-based assessments of systemic and pulmonary immune cells from LTBI participants and recipients of intradermal and oral BCG. LTBI individuals uniquely display ongoing immune activation and robust CD4 T cell recall responses in blood and lung. Intradermal BCG is associated …

Abnormal Patterns Of Sleep And Waking Behaviors Are Accompanied By Neocortical Oscillation Disturbances In An Ank3 Mouse Model Of Epilepsy-Bipolar Disorder Comorbidity, Juan E Villacres, Nicholas Riveira, Sohmee Kim, Laura L Colgin, Jeffrey L Noebels, Angel Y Lopez

Faculty, Staff and Students Publications

ANK3 is a leading bipolar disorder (BD) candidate gene in humans and provides a unique opportunity for studying epilepsy-BD comorbidity. Previous studies showed that deletion of Ank3-1b, a BD-associated variant of Ank3 in mice leads to increased firing threshold and diminished action potential dynamic range of parvalbumin (PV) interneurons and absence epilepsy, thus providing a biological mechanism linking epilepsy and BD. To explore the behavioral overlap of these disorders, we characterized behavioral patterns of Ank3-1b KO mice during overnight home-cage activity and examined network activity during these behaviors using paired video and EEG recordings. Since PV interneurons contribute to the …

The Effect Of Postoperative Naloxone In Certain Otolaryngologic Surgeries, Natalie M. Perlov, Sohan S. Shah, Joann Bluj, Zachary D. Urdang, Rebecca C. Chiffer

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: To evaluate the association of postoperative naloxone with the development of new substance use disorder (SUD), overdose, and death within 6 months of otolaryngologic surgery.

STUDY DESIGN: Retrospective cohort database study on TriNetX.

METHODS: Adult patients who underwent tonsil surgery (noncancerous), thyroid/parathyroid, septorhinoplasty, otology/neurotology, sinus/anterior skull base, and head and neck cancer surgeries between January 2003 and April 2023. Patients were excluded if they had an instance of SUD or overdose recorded in their charts prior to surgery, or had undergone another surgery within that 6-month time frame. We hypothesized that patients prescribed naloxone postoperatively would have decreased odds …

Targeted Therapeutic Strategies For Melanoma, Shiwei Zhang, Ruxin Xie, Ai Zhong, Junjie Chen

Faculty, Staff and Student Publications

Melanoma accounts for a small proportion of skin cancers diagnosed each year, but it has a high degree of malignancy and rapid progression, resulting in a short survival period for patients. The incidence of melanoma continues to rise, and now melanoma accounts for 1.7% of cancer diagnoses worldwide and is the fifth most common cancer in the United States. With the development of high-throughput sequencing technologies, the understanding of the pathophysiology of melanoma had also been improved. The most common activating mutations in melanoma cells are BRAF , NRAS , and KIT mutations, which disrupt cell signaling pathways related to …

The Concise Guide To Pharmacology 2023/24: Catalytic Receptors, Stephen P.H. Alexander, Doriano Fabbro, Eamonn Kelly, Alistair A. Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Jamie A. Davies, Annie Beuve, Peter Brouckaert, Clare Bryant, John C. Burnett, Richard W. Farndale, Andreas Friebe, John Garthwaite, Adrian J. Hobbs, Gavin E. Jarvis, Doris Koesling, Michaela Kuhn, David Macewan, Tom P. Monie, Lincoln R. Potter, Michael Russwurm, Harald H.H.W. Schmidt, Johannes-Peter Stasch, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It …

The Potential For Development Of Clinically Relevant Microbial Resistance To Rifaximin-Α: A Narrative Review, Herbert L Dupont

Faculty, Staff and Student Publications

Rifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile. While there are high concentrations of drug in the colon, low water solubility leads to low colonic drug bioavailability, protecting the gut microbiome. Rifaximin-α appears to be more active in the bile-rich small bowel. …

Research Priorities For Children’S Cancer: A James Lind Alliance Priority Setting Partnership In The Uk, Susie Aldiss, Rachel Hollis, Bob Phillips, Ashley Ball-Gamble, Alex Brownsdon, Julia Chisholm, Scott Crowther, Rachel Dommett, Jonathan Gower, Nigel J Hall, Helen Hartley, Jenni Hatton, Louise Henry, Loveday Langton, Kirsty Maddock, Sonia Malik, Keeley Mcevoy, Jessica Elizabeth Morgan, Helen Morris, Simon Parke, Sue Picton, Rosa Reed-Berendt, Dan Saunders, Andy Stewart, Wendy Tarplee-Morris, Amy Walsh, Anna Watkins, David Weller, Faith Gibson

Faculty, Staff and Student Publications

OBJECTIVES: To engage children who have experienced cancer, childhood cancer survivors, their families and professionals to systematically identify and prioritise research questions about childhood cancer to inform the future research agenda.

DESIGN: James Lind Alliance Priority Setting Partnership.

SETTING: UK health service and community.

METHODS: A steering group oversaw the initiative. Potential research questions were collected in an online survey, then checked to ensure they were unanswered. Shortlisting via a second online survey identified the highest priority questions. A parallel process with children was undertaken. A final consensus workshop was held to determine the Top 10 priorities.

PARTICIPANTS: Children and …

Bacterial Outer Membrane Vesicles Provide An Alternative Pathway For Trafficking Of Escherichia Coli O157 Type Iii Secreted Effectors To Epithelial Cells, Natalie Sirisaengtaksin, Eloise J O'Donoghue, Sara Jabbari, Andrew J Roe, Anne Marie Krachler

Faculty, Staff and Student Publications

Outer membrane vesicles (OMVs) are proteoliposomes shed by Gram-negative bacteria. Their secretion is enhanced by the transition into the intra-host milieu, and OMVs play critical roles during pathogenesis. Enterohemorrhagic Escherichia coli O157 (EHEC) can cause diarrheal disease in humans, and soluble toxins including Shiga-like toxins that contribute to disease severity and clinical complications like hemolytic uremic syndrome have been shown to be OMV associated. In addition to Shiga-like toxins, EHEC produces a type III secretion system (T3SS), and T3SS effectors are associated with colonization and disease severity in vivo. Here, we show that type III secreted substrates including translocators …

Colonization Of Larval Zebrafish (Danio Rerio) With Adherent-Invasive Escherichia Coli Prevents Recovery Of The Intestinal Mucosa From Drug-Induced Enterocolitis, Erika Flores, Soumita Dutta, Rachel Bosserman, Ambro Van Hoof, Anne-Marie Krachler

Faculty, Staff and Student Publications

Although inflammatory bowel diseases are on the rise, what factors influence IBD risk and severity, and the underlying mechanisms remain to be fully understood. Although host genetics, microbiome, and environmental factors have all been shown to correlate with the development of IBD, cause and effect are difficult to disentangle in this context. For example, AIEC is a known pathobiont found in IBD patients, but it remains unclear if gut inflammation during IBD facilitates colonization with AIEC, or if AIEC colonization makes the host more susceptible to pro-inflammatory stimuli. It is critical to understand the mechanisms that contribute to AIEC infections …

Rapidiron Trial Follow-Up Study - The Rapidiron-Kids Study: Protocol Of A Prospective Observational Follow-Up Study, Richard Derman, Roopa Bellad, Mrutyunjaya Bellad, Jesse Bradford-Rogers, Michael Georgieff, Zubair Aghai, Simal Thind, Michael Auerbach, Rupsa Boelig, Benjamin Leiby, Vanessa Short, S. Yogeshkumar, Umesh Charantimath, Manjunath Somannavar, Ashalata Mallapur, Ramesh Pol, Umesh Ramadurg, Radha Sangavi, Basavaraj Peerapur, Nasima Banu, Praveen Patil, Amaresh Patil, Subarna Roy, Phaniraj Vastrad, Dennis Wallace, Hemang Shah, Shivaprasad Goudar

Global Health Articles

BACKGROUND: Anemia is a worldwide problem with iron deficiency being the most common cause. When anemia occurs in pregnancy, it increases the risk of adverse maternal, fetal, and postnatal outcomes. It induces preterm births and low birth weight (LBW) deliveries, long-term neurodevelopmental sequelae, and an increased risk of earlier onset of postnatal iron deficiency. Anemia rates are among the highest in South Asia, and India's National Family Health Survey (NFHS-5) for 2019-2021 indicated that over half of pregnant women, and more than 65% of children, in the country are classified as anemic (Sciences IIfP, National Family Health Survey-5, 2019-21, India …

The Faculty-To-Faculty Mentorship Experience: A Survey On Challenges And Recommendations For Improvements, Sarvenaz Sarabipour, Natalie M Niemi, Steven J Burgess, Christopher T Smith, Alexandre W Bisson Filho, Ahmed Ibrahim, Kelly Clark

2020-Current year OA Pubs

Faculty at research institutions play a central role in advancing knowledge and careers, as well as promoting the well-being of students and colleagues in research environments. Mentorship from experienced peers has been touted as critical for enabling these myriad roles to allow faculty development, career progression, and satisfaction. However, there is little information available on who supports faculty and best ways to structure a faculty mentorship programme for early- and mid-career academics. In the interest of advocating for increased and enhanced faculty mentoring and mentoring programmes, we surveyed faculty around the world to gather data on whether and how they …

Mirna-211 Maintains Metabolic Homeostasis In Medulloblastoma Through Its Target Gene Long-Chain Acyl-Coa Synthetase 4, Menglang Yuan, Iqbal Mahmud, Keisuke Katsushima, Kandarp Joshi, Olivier Saulnier, Rudramani Pokhrel, Bongyong Lee, Wathsala Liyanage, Haritha Kunhiraman, Stacie Stapleton, Ignacio Gonzalez-Gomez, Rangaramanujam M Kannan, Tanja Eisemann, Elayaraja Kolanthai, Sudipta Seal, Timothy J Garrett, Saed Abbasi, Kimberly Bockley, Justin Hanes, Prem Chapagain, George Jallo, Robert J Wechsler-Reya, Michael D Taylor, Charles G Eberhart, Animesh Ray, Ranjan J Perera

Faculty, Staff and Students Publications

The prognosis of childhood medulloblastoma (MB) is often poor, and it usually requires aggressive therapy that adversely affects quality of life. microRNA-211 (miR-211) was previously identified as an important regulator of cells that descend from neural cells. Since medulloblastomas primarily affect cells with similar ontogeny, we investigated the role and mechanism of miR-211 in MB. Here we showed that miR-211 expression was highly downregulated in cell lines, PDXs, and clinical samples of different MB subgroups (SHH, Group 3, and Group 4) compared to normal cerebellum. miR-211 gene was ectopically expressed in transgenic cells from MB subgroups, and they were subjected …

Rotavirus-Mediated Dgat1 Degradation: A Pathophysiological Mechanism Of Viral-Induced Malabsorptive Diarrhea, Zheng Liu, Hunter Smith, Jeanette M Criglar, Antonio J Valentin, Umesh Karandikar, Xi-Lei Zeng, Mary K Estes, Sue E Crawford

Faculty, Staff and Students Publications

Gastroenteritis is among the leading causes of mortality globally in infants and young children, with rotavirus (RV) causing ~258 million episodes of diarrhea and ~128,000 deaths annually in infants and children. RV-induced mechanisms that result in diarrhea are not completely understood, but malabsorption is a contributing factor. RV alters cellular lipid metabolism by inducing lipid droplet (LD) formation as a platform for replication factories named viroplasms. A link between LD formation and gastroenteritis has not been identified. We found that diacylglycerol O-acyltransferase 1 (DGAT1), the terminal step in triacylglycerol synthesis required for LD biogenesis, is degraded in RV-infected cells by …

Advanced Structural Brain Aging In Preclinical Autosomal Dominant Alzheimer Disease, Peter R Millar, Brian A Gordon, Julie K Wisch, Tammie L.S. Benzinger, Carlos Cruchaga, Jason J Hassenstab, Laura Ibanez, Celeste Karch, Jorge J Llibre-Guerra, John C Morris, Richard J Perrin, Charlene Supnet-Bell, Chengjie Xiong, Randall J Bateman, Beau M Ances, Eric M Mcdade, Et Al.

2020-Current year OA Pubs

BACKGROUND: "Brain-predicted age" estimates biological age from complex, nonlinear features in neuroimaging scans. The brain age gap (BAG) between predicted and chronological age is elevated in sporadic Alzheimer disease (AD), but is underexplored in autosomal dominant AD (ADAD), in which AD progression is highly predictable with minimal confounding age-related co-pathology.

METHODS: We modeled BAG in 257 deeply-phenotyped ADAD mutation-carriers and 179 non-carriers from the Dominantly Inherited Alzheimer Network using minimally-processed structural MRI scans. We then tested whether BAG differed as a function of mutation and cognitive status, or estimated years until symptom onset, and whether it was associated with established …

Blue-Shift Photoconversion Of Near-Infrared Fluorescent Proteins For Labeling And Tracking In Living Cells And Organisms, Francesca Pennacchietti, Jonatan Alvelid, Rodrigo A Morales, Martina Damenti, Dirk Ollech, Olena S Oliinyk, Daria M Shcherbakova, Eduardo J Villablanca, Vladislav V Verkhusha, Ilaria Testa

Faculty, Staff and Student Publications

Photolabeling of intracellular molecules is an invaluable approach to studying various dynamic processes in living cells with high spatiotemporal precision. Among fluorescent proteins, photoconvertible mechanisms and their products are in the visible spectrum (400-650 nm), limiting their in vivo and multiplexed applications. Here we report the phenomenon of near-infrared to far-red photoconversion in the miRFP family of near infrared fluorescent proteins engineered from bacterial phytochromes. This photoconversion is induced by near-infrared light through a non-linear process, further allowing optical sectioning. Photoconverted miRFP species emit fluorescence at 650 nm enabling photolabeling entirely performed in the near-infrared range. We use miRFPs as …

Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

ncreased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE₂/EP2 feedforward loop, …