Medicine and Health Sciences Commons^™

Cardiovascular Disease Management With Sodium-Glucose Cotransporter-2 Inhibitors In Patients With Type 2 Diabetes: A Cardiology Primer, Stephanie A Coulter, Salim Virani, Kershaw V Patel, Matthew W Segar

Faculty, Staff and Students Publications

Patients with type 2 diabetes face an elevated risk of cardiovascular disease. This review centers on sodium-glucose cotransporter-2 (SGLT2) inhibitors, a class of drugs that, according to a growing body of evidence, may have major potential for managing cardiovascular disease in patients with type 2 diabetes. This review presents findings from multiple clinical trials suggesting that SGLT2 inhibitors can not only serve as preventive therapeutic agents but also play a role in the active management of heart failure. The discussion includes the mechanism of action of SGLT2 inhibitors, emphasizing that they enhance urinary glucose excretion, which could lead to improved …

Nanocavity-Mediated Purcell Enhancement Of Er In Tio2 Thin Films Grown Via Atomic Layer Deposition, Muchuan Hua, Jianguo Wen, Sagar Kumar Seth, Connor P Horn, Ignas Masiulionis, Manish Kumar Singh, Sean E Sullivan, F Joseph Heremans, David D Awschalom, Supratik Guha, Alan M Dibos

Faculty, Staff and Student Publications

The use of trivalent erbium (Er3+), typically embedded as an atomic defect in the solid-state, has widespread adoption as a dopant in telecommunication devices and shows promise as a spin-based quantum memory for quantum communication. In particular, its natural telecom C-band optical transition and spin-photon interface make it an ideal candidate for integration into existing optical fiber networks without the need for quantum frequency conversion. However, successful scaling requires a host material with few intrinsic nuclear spins, compatibility with semiconductor foundry processes, and straightforward integration with silicon photonics. Here, we present Er-doped titanium dioxide (TiO2) thin film growth on silicon …

Chromatin Profiles Are Prognostic Of Clinical Response To Bortezomib-Containing Chemotherapy In Pediatric Acute Myeloid Leukemia: Results From The Cog Aaml1031 Trial, Anneke D Van Dijk, Fieke W Hoff, Yihua Qiu, Stefan E Hubner, Robin L Go, Amanda R Leonti, Alan S Gamis, Richard Aplenc, Edward A Kolb, Todd A Alonzo, Soheil Meshinchi, Eveline S J M De Bont, Terzah M Horton, Steven M Kornblau

Faculty, Staff and Student Publications

The addition of the proteasome inhibitor bortezomib to standard chemotherapy did not improve survival in pediatric acute myeloid leukemia (AML) when all patients were analyzed as a group in the Children's Oncology Group phase 3 trial AAML1031 (NCT01371981). Proteasome inhibition influences the chromatin landscape and proteostasis, and we hypothesized that baseline proteomic analysis of histone- and chromatin-modifying enzymes (HMEs) would identify AML subgroups that benefitted from bortezomib addition. A proteomic profile of 483 patients treated with AAML1031 chemotherapy was generated using a reverse-phase protein array. A relatively high expression of 16 HME was associated with lower EFS and …

The Role Of Computational Methods In Cardiovascular Medicine: A Narrative Review, Gerard E Francisco

Faculty, Staff and Student Publications

Botulinum toxin type-A (BoNT-A) has emerged as a key therapeutic agent for the management of spasticity. This paper presents a comprehensive bibliometric and visual analysis of research concerning BoNT-A treatment of spasticity to elucidate current trends and future directions in this research area. A search was conducted in the Web of Science database for articles focused on the use of BoNT-A in spasticity published between 2000 and 2022. We extracted various metrics, including counts of publications and contributions from different countries, institutions, authors, and journals. Analytical methods in CiteSpace were employed for the examination of co-citations, collaborations, and the co-occurrence …

Patient Characteristics Of, And Remedial Interventions For, Complaints And Medico-Legal Claims Against Doctors: A Rapid Review Of The Literature, Richard Clark, Michael Wright

Faculty, Staff and Student Publications

BACKGROUND: It is uncertain if patient's characteristics are associated with complaints and claims against doctors. Additionally, evidence for the effectiveness of remedial interventions on rates of complaints and claims against doctors has not been synthesised.

METHODS: We conducted a rapid review of recent literature to answer: Question 1 "What are the common characteristics and circumstances of patients who are most likely to complain or bring a claim about the care they have received from a doctor?" and Question 2 "What initiatives or interventions have been shown to be effective at reducing complaints and claims about the care patients have received …

Funcpep V20: An Updated Database Of Functional Short Peptides Translated From Non-Coding Rnas, Swati Mohapatra, Anik Banerjee, Paola Rausseo, Mihnea P Dragomir, Ganiraju C Manyam, George A Calin

Faculty, Staff and Student Publications

Over the past decade, there have been reports of short novel functional peptides (less than 100 aa in length) translated from so-called non-coding RNAs (ncRNAs) that have been characterized using mass spectrometry (MS) and large-scale proteomics studies. Therefore, understanding the bivalent functions of some ncRNAs as transcripts that encode both functional RNAs and short peptides, which we named ncPEPs, will deepen our understanding of biology and disease. In 2020, we published the first database of functional peptides translated from non-coding RNAs-FuncPEP. Herein, we have performed an update including the newly published ncPEPs from the last 3 years along with the …

Funcpep V20: An Updated Database Of Functional Short Peptides Translated From Non-Coding Rnas, Swati Mohapatra, Anik Banerjee, Paola Rausseo, Mihnea P Dragomir, Ganiraju C Manyam, George A Calin

Faculty, Staff and Student Publications

Over the past decade, there have been reports of short novel functional peptides (less than 100 aa in length) translated from so-called non-coding RNAs (ncRNAs) that have been characterized using mass spectrometry (MS) and large-scale proteomics studies. Therefore, understanding the bivalent functions of some ncRNAs as transcripts that encode both functional RNAs and short peptides, which we named ncPEPs, will deepen our understanding of biology and disease. In 2020, we published the first database of functional peptides translated from non-coding RNAs-FuncPEP. Herein, we have performed an update including the newly published ncPEPs from the last 3 years along with the …

Wnk Kinase Is A Vasoactive Chloride Sensor In Endothelial Cells, Daniel M Collier

Faculty, Staff and Student Publications

Endothelial cells (ECs) line the wall of blood vessels and regulate arterial contractility to tune regional organ blood flow and systemic pressure. Chloride (Cl-) is the most abundant anion in ECs and the Cl- sensitive With-No-Lysine (WNK) kinase is expressed in this cell type. Whether intracellular Cl- signaling and WNK kinase regulate EC function to alter arterial contractility is unclear. Here, we tested the hypothesis that intracellular Cl- signaling in ECs regulates arterial contractility and examined the signaling mechanisms involved, including the participation of WNK kinase. Our data obtained using two-photon microscopy and cell-specific inducible knockout mice indicated that acetylcholine, …

Publisher Correction: Ndufs4 Regulates Cristae Remodeling In Diabetic Kidney Disease, Zengchun Ye, Guizhen Fan, Rajesh Sharma, Irina I Serysheva, Travis I Moore, Collene R Jeter, M Anna Zal, Motoo Araki, Jun Wada, Paul T Schumacker, Benny H Chang, Farhad R Danesh

Faculty, Staff and Students Publications

No abstract provided.

Prognostic Significance Of Central Skull Base Remodeling In Chiari Ii Malformation, William E Whitehead, Thierry A G M Huisman

Faculty, Staff and Students Publications

Background and purpose: Outward convexity of the basiocciput and posterior atlanto-occipital membrane are common in patients with Chiari II malformation associated with an open neural tube defect. We aimed to determine if the severity of these findings correlated with the need for future hydrocephalus treatment.

Materials and methods: A retrospective chart and imaging review identified patients who underwent open neural tube defect repair at a quaternary care pediatric hospital from July 2014 through September 2022. Patients were classified by the need for hydrocephalus treatment and whether they received prenatal or postnatal neural tube defect repair. Measurements of imaging parameters related …

Mir-574-5p Activates Human Tlr8 To Promote Autoimmune Signaling And Lupus, Dianqiang Yang, Yida Xing, Shulin Bi, Yan Zhang, Tao Hu, Yunyun Zhang, Shuang Dai, Zhiqiang Shao, Dahan Chen, Jinpao Hou, Esteban Ballestar, Jianchun Cai, Feng Zheng, James Y Yang

Faculty, Staff and Student Publications

Endosomal single-stranded RNA-sensing Toll-like receptor-7/8 (TLR7/8) plays a pivotal role in inflammation and immune responses and autoimmune diseases. However, the mechanisms underlying the initiation of the TLR7/8-mediated autoimmune signaling remain to be fully elucidated. Here, we demonstrate that miR-574-5p is aberrantly upregulated in tissues of lupus prone mice and in the plasma of lupus patients, with its expression levels correlating with the disease activity. miR-574-5p binds to and activates human hTLR8 or its murine ortholog mTlr7 to elicit a series of MyD88-dependent immune and inflammatory responses. These responses include the overproduction of cytokines and interferons, the activation of STAT1 signaling …

The Roles Of Ferroptosis In Cancer: Tumor Suppression, Tumor Microenvironment, And Therapeutic Interventions, Guang Lei, Li Zhuang, Boyi Gan

Faculty, Staff and Student Publications

In cancer treatment, the recurrent challenge of inducing apoptosis through conventional therapeutic modalities, often thwarted by therapy resistance, emphasizes the critical need to explore alternative cell death pathways. Ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides on cellular membranes, has emerged as one such promising frontier in oncology. Induction of ferroptosis not only suppresses tumor growth but also holds potential for augmenting immunotherapy responses and surmounting resistance to existing cancer therapies. This review navigates the role of ferroptosis in tumor suppression. Furthermore, we delve into the complex role of ferroptosis within the …

A Structured Curriculum Supporting Biomedical Trainees’ Transition Into Independent Academic Positions And Early Career Success, Mabel Perez-Oquendo, Gabriele Romano, David P Farris, Varsha Gandhi, Ignacio I Wistuba, Ryan Udan, Rama Soundararajan

Faculty, Staff and Student Publications

The United States government makes a substantial investment in biomedical training programs each year. However, for most trainees, these opportunities do not translate into career progression in academic research pathways. Only about one-fifth of postdoctoral fellows eventually secure a tenure-track faculty position, and even among these candidates, attrition is high. Although a number of factors govern career choices and career longevity, the transition from trainee to faculty is a challenging process and requires knowledge and skills that are not necessarily developed during a traditional university experience. Many postdoctoral fellows receive adequate training in research skills and scientific communication, but new …

Arterial Spin-Labeling And Dsc Perfusion Metrics Improve Agreement In Neuroradiologists' Clinical Interpretations Of Posttreatment High-Grade Glioma Surveillance Mr Imaging-An Institutional Experience, Ghiam Yamin, Eric Tranvinh, Bryan A Lanzman, Elizabeth Tong, Syed S Hashmi, Michael Iv

Faculty, Staff and Student Publications

Background and purpose: MR perfusion has shown value in the evaluation of posttreatment high-grade gliomas, but few studies have shown its impact on the consistency and confidence of neuroradiologists' interpretation in routine clinical practice. We evaluated the impact of adding MR perfusion metrics to conventional contrast-enhanced MR imaging in posttreatment high-grade glioma surveillance imaging.

Materials and methods: This retrospective study included 45 adults with high-grade gliomas who had posttreatment perfusion MR imaging. Four neuroradiologists assigned Brain Tumor Reporting and Data System scores for each examination on the basis of the interpretation of contrast-enhanced MR imaging and then after the addition …

Author Correction: Comparative Analysis Of Dimension Reduction Methods For Cytometry By Time-Of-Flight Data, Kaiwen Wang, Yuqiu Yang, Fangjiang Wu, Bing Song, Xinlei Wang

Faculty, Staff and Student Publications

No abstract provided.

Arid1a Orchestrates Swi/Snf-Mediated Sequential Binding Of Transcription Factors With Arid1a Loss Driving Pre-Memory B Cell Fate And Lymphomagenesis, Darko Barisic, Christopher R Chin, Cem Meydan, Matt Teater, Ioanna Tsialta, Amy Chadburn, Margot Sarkozy, Min Xia, Sandra E Carson, Santo Raggiri, Sonia Debek, Benedikt Pelzer, Ceyda Durmaz, Qing Deng, Priya Lakra, Martin Rivas, Christian Steidl, David W Scott, Andrew P Weng, Christopher E Mason, Michael R Green, Ari Melnick

Faculty, Staff and Student Publications

ARID1A, a subunit of the canonical BAF nucleosome remodeling complex, is commonly mutated in lymphomas. We show that ARID1A orchestrates B cell fate during the germinal center (GC) response, facilitating cooperative and sequential binding of PU.1 and NF-kB at crucial genes for cytokine and CD40 signaling. The absence of ARID1A tilts GC cell fate toward immature IgM+CD80-PD-L2- memory B cells, known for their potential to re-enter new GCs. When combined with BCL2 oncogene, ARID1A haploinsufficiency hastens the progression of aggressive follicular lymphomas (FLs) in mice. Patients with FL with ARID1A-inactivating mutations preferentially display an immature memory B cell-like state with …

Single-Cell Systems Pharmacology Identifies Development-Driven Drug Response And Combination Therapy In B Cell Acute Lymphoblastic Leukemia, Xin Huang, Yizhen Li, Jingliao Zhang, Lei Yan, Huanbin Zhao, Sheetal Bhatara, Satoshi Yoshimura, Wenjian Yang, Seth E Karol, Hiroto Inaba, Charles Mullighan, Mark Litzow, Xiaofan Zhu, Yingchi Zhang, Wendy Stock, Nitin Jain, Elias Jabbour, Steven M Kornblau, Marina Konopleva, Ching-Hon Pui, Elisabeth Paietta, William Evans, Jiyang Yu, Jun J Yang

Faculty, Staff and Student Publications

Leukemia can arise at various stages of the hematopoietic differentiation hierarchy, but the impact of developmental arrest on drug sensitivity is unclear. Applying network-based analyses to single-cell transcriptomes of human B cells, we define genome-wide signaling circuitry for each B cell differentiation stage. Using this reference, we comprehensively map the developmental states of B cell acute lymphoblastic leukemia (B-ALL), revealing its strong correlation with sensitivity to asparaginase, a commonly used chemotherapeutic agent. Single-cell multi-omics analyses of primary B-ALL blasts reveal marked intra-leukemia heterogeneity in asparaginase response: resistance is linked to pre-pro-B-like cells, with sensitivity associated with the pro-B-like population. By …

Smarca4 Is A Haploinsufficient B Cell Lymphoma Tumor Suppressor That Fine-Tunes Centrocyte Cell Fate Decisions, Qing Deng, Priya Lakra, Panhong Gou, Haopeng Yang, Cem Meydan, Christopher Chin, Tommy Dinh, Usama Hussein, Xubin Li, Estela Rojas, Weiguang Liu, Patrick K Reville, Atish Kizhakeyil, Darko Barisic, Sydney Parsons, Ashley Wilson, Jared Henderson, Brooks Scull, Channabasavaiah Gurumurthy, Francisco Vega, Amy Chadburn, Branko Cuglievan, Nader Kim El-Mallawany, Carl Allen, Christopher Mason, Ari Melnick, Michael R Green

Faculty, Staff and Student Publications

SMARCA4 encodes one of two mutually exclusive ATPase subunits in the BRG/BRM associated factor (BAF) complex that is recruited by transcription factors (TFs) to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ∼30% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency cooperated with MYC over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of TFs that are activated in centrocytes to drive GC-exit, including SPI1 …

Comparison Of Two Formulations Of Intravenous Lipid Emulsions In Pediatric Intestinal Failure, Mamta Naik, Alexandria Lawrence, Allison Davidson, John Chapman, Dalya Ferguson, Allison L Speer, Essam Imseis

Faculty, Staff and Student Publications

Purpose: The effect of different types of lipid emulsion may guide therapy of patients with intestinal failure (IF) to limit morbidity such as intestinal failure-associated liver disease (IFALD).

Methods: A retrospective chart review of pediatric patients with IF who received soybean oil lipid emulsion (SL) or mixed oil lipid emulsion (ML) was performed. Data over 1 year were collected.

Results: Forty-five patients received SL and 34 received ML. There were no differences in the incidence (82 versus 74%, P = 0.35) or resolution (86 versus 92%, P = 0.5) of IFALD between the cohorts. The median dose of ML was …

Islet Autoantibodies As Precision Diagnostic Tools To Characterize Heterogeneity In Type 1 Diabetes: A Systematic Review, Cate Speake, S Alice Long, Suna Onengut-Gumuscu, Stephen S Rich, Gabriela S F Monaco, Arianna Harris-Kawano, Dianna Perez, Zeb Saeed, Benjamin Hoag, Rashmi Jain, Carmella Evans-Molina, Linda A Dimeglio, Heba M Ismail, Dana Dabelea, Randi K Johnson, Marzhan Urazbayeva, John M Wentworth, Kurt J Griffin, Emily K Sims, Ada/Easd Pmdi Collaborators

Faculty, Staff and Students Publications

BACKGROUND: Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized that autoantibodies can identify heterogeneity before, at, and after T1D diagnosis, and in response to disease-modifying therapies.

METHODS: We systematically reviewed PubMed and EMBASE databases (6/14/2022) assessing 10 years of original research examining relationships between autoantibodies and heterogeneity before, at, after diagnosis, and in response to disease-modifying therapies in individuals at-risk or within 1 year of T1D diagnosis. A critical appraisal checklist tool for cohort studies was modified and used for risk of bias assessment.

RESULTS: …

Cannabis Use Associated With Lower Mortality Among Hospitalized Covid-19 Patients Using The National Inpatient Sample: An Epidemiological Study

Faculty, Staff and Students Publications

BACKGROUND: Prior reports indicate that modulation of the endocannabinoid system (ECS) may have a protective benefit for Covid-19 patients. However, associations between cannabis use (CU) or CU not in remission (active cannabis use (ACU)), and Covid-19-related outcomes among hospitalized patients is unknown.

METHODS: In this multicenter retrospective observational cohort analysis of adults (≥ 18 years-old) identified from 2020 National Inpatient Sample database, we utilize multivariable regression analyses and propensity score matching analysis (PSM) to analyze trends and outcomes among Covid-19-related hospitalizations with CU and without CU (N-CU) for primary outcome of interest: Covid-19-related mortality; and secondary outcomes: Covid-19-related hospitalization, mechanical …

Cannabis Use Associated With Lower Mortality Among Hospitalized Covid-19 Patients Using The National Inpatient Sample: An Epidemiological Study

Faculty, Staff and Students Publications

BACKGROUND: Prior reports indicate that modulation of the endocannabinoid system (ECS) may have a protective benefit for Covid-19 patients. However, associations between cannabis use (CU) or CU not in remission (active cannabis use (ACU)), and Covid-19-related outcomes among hospitalized patients is unknown.

METHODS: In this multicenter retrospective observational cohort analysis of adults (≥ 18 years-old) identified from 2020 National Inpatient Sample database, we utilize multivariable regression analyses and propensity score matching analysis (PSM) to analyze trends and outcomes among Covid-19-related hospitalizations with CU and without CU (N-CU) for primary outcome of interest: Covid-19-related mortality; and secondary outcomes: Covid-19-related hospitalization, mechanical …

Enhanced Plant-Derived Vesicles For Nucleotide Delivery For Cancer Therapy, Sara Corvigno, Yuan Liu, Emine Bayraktar, Elaine Stur, Nazende Nur Bayram, Supriya Nagaraju, Hu Chen, Thanh Chung Vu, Yunfei Wen, Han Liang, Li Zhao, Sanghoon Lee, Gabriel Lopez-Berestein, Anil K Sood

Faculty, Staff and Student Publications

Small RNAs (microRNAs [miRNAs] or small interfering RNAs [siRNAs]) are effective tools for cancer therapy, but many of the existing carriers for their delivery are limited by low bioavailability, insufficient loading, impaired transport across biological barriers, and low delivery into the tumor microenvironment. Extracellular vesicle (EV)-based communication in mammalian and plant systems is important for many physiological and pathological processes, and EVs show promise as carriers for RNA interference molecules. However, some fundamental issues limit their use, such as insufficient cargo loading and low potential for scaling production. Plant-derived vesicles (PDVs) are membrane-coated vesicles released in the apoplastic fluid of …

Neighborhood Light At Night And Noise Levels, And Long-Term Sleep Trajectories In The Southern Community Cohort Study

Faculty, Staff and Student Publications

While light at night (LAN) and noise levels have been linked to suboptimal sleep outcomes, little is known about the link between these factors and long-term suboptimal sleep trajectories. The current study examined the association of neighborhood LAN and nighttime noise with long-term sleep trajectories in a cohort of Black individuals and White individuals predominantly from low-income communities. We used data from the Southern Community Cohort Study (N = 28,759 Black individuals and 16,276 White individuals). Sleep duration was self-reported at baseline and after an average of five years of follow-up, based on which we constructed nine sleep trajectories: normal-normal …

Deepdof-Se: Affordable Deep-Learning Microscopy Platform For Slide-Free Histology

Faculty, Staff and Student Publications

Histopathology plays a critical role in the diagnosis and surgical management of cancer. However, access to histopathology services, especially frozen section pathology during surgery, is limited in resource-constrained settings because preparing slides from resected tissue is time-consuming, labor-intensive, and requires expensive infrastructure. Here, we report a deep-learning-enabled microscope, named DeepDOF-SE, to rapidly scan intact tissue at cellular resolution without the need for physical sectioning. Three key features jointly make DeepDOF-SE practical. First, tissue specimens are stained directly with inexpensive vital fluorescent dyes and optically sectioned with ultra-violet excitation that localizes fluorescent emission to a thin surface layer. Second, a deep-learning …

Unsupervised Deep Representation Learning Enables Phenotype Discovery For Genetic Association Studies Of Brain Imaging, Yaochen Xie, Assaf Gottlieb, Han Chen, Luca Giancardo, Alexander Knaack, Evan Fletcher, Myriam Fornage, Shuiwang Ji, Degui Zhi

Faculty, Staff and Student Publications

Understanding the genetic architecture of brain structure is challenging, partly due to difficulties in designing robust, non-biased descriptors of brain morphology. Until recently, brain measures for genome-wide association studies (GWAS) consisted of traditionally expert-defined or software-derived image-derived phenotypes (IDPs) that are often based on theoretical preconceptions or computed from limited amounts of data. Here, we present an approach to derive brain imaging phenotypes using unsupervised deep representation learning. We train a 3-D convolutional autoencoder model with reconstruction loss on 6130 UK Biobank (UKBB) participants' T1 or T2-FLAIR (T2) brain MRIs to create a 128-dimensional representation known as Unsupervised Deep learning …

Application Of Deep Learning On Mammographies To Discriminate Between Low And High-Risk Dcis For Patient Participation In Active Surveillance Trials, Sena Alaeikhanehshir, Madelon M Voets, Frederieke H Van Duijnhoven, Esther H Lips, Emma J Groen, Shelley E Hwang, Jelle Wesseling, Ritse M Mann, Jonas Teuwen

Faculty, Staff and Student Publications

BACKGROUND: Ductal Carcinoma In Situ (DCIS) can progress to invasive breast cancer, but most DCIS lesions never will. Therefore, four clinical trials (COMET, LORIS, LORETTA, AND LORD) test whether active surveillance for women with low-risk Ductal carcinoma In Situ is safe (E. S. Hwang et al., BMJ Open, 9: e026797, 2019, A. Francis et al., Eur J Cancer. 51: 2296-2303, 2015, Chizuko Kanbayashi et al. The international collaboration of active surveillance trials for low-risk DCIS (LORIS, LORD, COMET, LORETTA), L. E. Elshof et al., Eur J Cancer, 51, 1497-510, 2015). Low-risk is defined as grade I or II DCIS. Because …

Deparylation Is Critical For S Phase Progression And Cell Survival, Litong Nie, Chao Wang, Min Huang, Xiaoguang Liu, Xu Feng, Siting Li, Hongqi Teng, Xi Shen, Li Ma, Boyi Gan, Junjie Chen

Faculty, Staff and Student Publications

Poly(ADP-ribose)ylation or PARylation by PAR polymerase 1 (PARP1) and dePARylation by poly(ADP-ribose) glycohydrolase (PARG) are equally important for the dynamic regulation of DNA damage response. PARG, the most active dePARylation enzyme, is recruited to sites of DNA damage via pADPr-dependent and PCNA-dependent mechanisms. Targeting dePARylation is considered an alternative strategy to overcome PARP inhibitor resistance. However, precisely how dePARylation functions in normal unperturbed cells remains elusive. To address this challenge, we conducted multiple CRISPR screens and revealed that dePARylation of S phase pADPr by PARG is essential for cell viability. Loss of dePARylation activity initially induced S-phase-specific pADPr signaling, which …

Human Brain Glycoform Coregulation Network And Glycan Modification Alterations In Alzheimer's Disease, Qi Zhang, Cheng Ma, Lih-Shen Chin, Sheng Pan, Lian Li

Faculty, Staff and Student Publications

Despite the importance of protein glycosylation to brain health, current knowledge of glycosylated proteoforms or glycoforms in human brain and their alterations in Alzheimer's disease (AD) is limited. Here, we report a proteome-wide glycoform profiling study of human AD and control brains using intact glycopeptide-based quantitative glycoproteomics coupled with systems biology. Our study identified more than 10,000 human brain N-glycoforms from nearly 1200 glycoproteins and uncovered disease signatures of altered glycoforms and glycan modifications, including reduced sialylation and N-glycan branching and elongation as well as elevated mannosylation and N-glycan truncation in AD. Network analyses revealed a higher-order organization of brain …

The Saga Of E Faecium, Rishika Prasad, Robert R Jenq

Faculty, Staff and Student Publications

An enzyme that remodels the cell wall of Enterococcus faecium helps these gut bacteria to divide and generate peptide fragments that enhance the immune response against cancer.