Digital Commons Network^™

Mitochondrial Pyruvate Carrier Inhibitors Improve Metabolic Parameters In Diet-Induced Obese Mice, Wesley T Hodges, Chaowapong Jarasvaraparn, Daniel Ferguson, Kristine Griffett, Lauren E Gill, Yana Chen, Ma Xenia G Ilagan, Lamees Hegazy, Bahaa Elgendy, Kevin Cho, Gary J Patti, Kyle S Mccommis, Brian N Finck

Open Access Publications

The mitochondrial pyruvate carrier (MPC) is an inner mitochondrial membrane complex that plays a critical role in intermediary metabolism. Inhibition of the MPC, especially in liver, may have efficacy for treating type 2 diabetes mellitus. Herein, we examined the antidiabetic effects of zaprinast and 7ACC2, small molecules which have been reported to act as MPC inhibitors. Both compounds activated a bioluminescence resonance energy transfer-based MPC reporter assay (reporter sensitive to pyruvate) and potently inhibited pyruvate-mediated respiration in isolated mitochondria. Furthermore, zaprinast and 7ACC2 acutely improved glucose tolerance in diet-induced obese mice in vivo. Although some findings were suggestive of improved …

The Foundations And Development Of Lipidomics, Xianlin Han, Richard W Gross

Open Access Publications

For over a century, the importance of lipid metabolism in biology was recognized but difficult to mechanistically understand due to the lack of sensitive and robust technologies for identification and quantification of lipid molecular species. The enabling technological breakthroughs emerged in the 1980s with the development of soft ionization methods (Electrospray Ionization and Matrix Assisted Laser Desorption/Ionization) that could identify and quantify intact individual lipid molecular species. These soft ionization technologies laid the foundations for what was to be later named the field of lipidomics. Further innovative advances in multistage fragmentation, dramatic improvements in resolution and mass accuracy, and multiplexed …

Coronavirus Disease 2019 (Covid-19) Research Agenda For Healthcare Epidemiology, Lona Mody, Hilary M Babcock, Jennie H Kwon, Et Al

Open Access Publications

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based …

Antiretroviral Therapy Timing Impacts Latent Tuberculosis Infection Reactivation In A Mycobacterium Tuberculosis/Siv Coinfection Model, Riti Sharan, Allison N Bucsan, Shabaana A Khader, Et Al

Open Access Publications

Studies using the nonhuman primate model of Mycobacterium tuberculosis/simian immunodeficiency virus coinfection have revealed protective CD4+ T cell-independent immune responses that suppress latent tuberculosis infection (LTBI) reactivation. In particular, chronic immune activation rather than the mere depletion of CD4+ T cells correlates with reactivation due to SIV coinfection. Here, we administered combinatorial antiretroviral therapy (cART) 2 weeks after SIV coinfection to study whether restoration of CD4+ T cell immunity occurred more broadly, and whether this prevented reactivation of LTBI compared to cART initiated 4 weeks after SIV. Earlier initiation of cART enhanced survival, led to better control of viral replication, …

The Ascc2 Cue Domain In The Alkbh3-Ascc Dna Repair Complex Recognizes Adjacent Ubiquitins In K63-Linked Polyubiquitin, Patrick M Lombardi, Timur Rusanov, Rebecca Rodell, Nima Mosammaparast, Et Al

Open Access Publications

Alkylation of DNA and RNA is a potentially toxic lesion that can result in mutations and even cell death. In response to alkylation damage, K63-linked polyubiquitin chains are assembled that localize the Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3-Activating Signal Cointegrator 1 Complex Subunit (ASCC) repair complex to damage sites in the nucleus. The protein ASCC2, a subunit of the ASCC complex, selectively binds K63-linked polyubiquitin chains via its coupling of ubiquitin conjugation to ER degradation (CUE) domain. The basis for polyubiquitin-binding specificity was unclear, because CUE domains in other proteins typically bind a single ubiquitin and do not discriminate among different …

Enzymatic And Structural Characterization Of Had5, An Essential Phosphomannomutase Of Malaria-Causing Parasites, Philip M Frasse, Justin J Miller, Alexander J Polino, Ebrahim Soleimani, Jian-She Zhu, David L Jakeman, Joseph M Jez, Daniel E Goldberg, Audrey R Odom John

Open Access Publications

The malaria-causing parasite Plasmodium falciparum is responsible for over 200 million infections and 400,000 deaths per year. At multiple stages during its complex life cycle, P. falciparum expresses several essential proteins tethered to its surface by glycosylphosphatidylinositol (GPI) anchors, which are critical for biological processes such as parasite egress and reinvasion of host red blood cells. Targeting this pathway therapeutically has the potential to broadly impact parasite development across several life stages. Here, we characterize an upstream component of parasite GPI anchor biosynthesis, the putative phosphomannomutase (PMM) (EC 5.4.2.8), HAD5 (PF3D7_1017400). We confirmed the PMM and phosphoglucomutase activities of purified …

Liposomal Phytohemagglutinin: In Vivo T-Cell Activator As A Novel Pan-Cancer Immunotherapy, Kinan Alhallak, Jennifer Sun, Barbara Muz, Amanda Jeske, Julie O'Neal, Julie K Ritchey, Samuel Achilefu, John F Dipersio, Abdel Kareem Azab

Open Access Publications

Immunotherapy is an attractive approach for treating cancer. T-cell engagers (TCEs) are a type of immunotherapy that are highly efficacious; however, they are challenged by weak T-cell activation and short persistence. Therefore, alternative solutions to induce greater activation and persistence of T cells during TCE immunotherapy is needed. Methods to activate T cells include the use of lectins, such as phytohemagglutinin (PHA). PHA has not been used to activate T cells in vivo, for immunotherapy, due to its biological instability and toxicity. An approach to overcome the limitations of PHA while also preserving its function is needed. In this study, …

Quantifying Regional Α -Synuclein, Amyloid Β, And Tau Accumulation In Lewy Body Dementia, Rebecca L Miller, Dhruva D Dhavale, Jennifer Y O'Shea, Kristin M Andruska, Jialu Liu, Erin E Franklin, Chandana Buddhala, Susan K Loftin, John R Cirrito, Richard J Perrin, Nigel J Cairns, Meghan C Campbell, Joel S Perlmutter, Paul T Kotzbauer

Open Access Publications

OBJECTIVE: Parkinson disease (PD) is defined by the accumulation of misfolded α-synuclein (α-syn) in Lewy bodies and Lewy neurites. It affects multiple cortical and subcortical neuronal populations. The majority of people with PD develop dementia, which is associated with Lewy bodies in neocortex and referred to as Lewy body dementia (LBD). Other neuropathologic changes, including amyloid β (Aβ) and tau accumulation, occur in some LBD cases. We sought to quantify α-syn, Aβ, and tau accumulation in neocortical, limbic, and basal ganglia regions.

METHODS: We isolated insoluble protein from fresh frozen postmortem brain tissue samples for eight brains regions from 15 …

A Unique Sarcopenic Progression In The Mouse Rotator Cuff, Gretchen A Meyer, Karen C Shen

2020-Current year OA Pubs

BACKGROUND: In response to chronic injury, the muscles of the rotator cuff (RC) experience a unique degeneration characterized by extensive fatty infiltration and loss of contractile function. Human studies suggest this degeneration is also a feature of RC sarcopenia and may precede RC injury. In this study, we investigated whether RC muscles exhibit a similar unique sarcopenia in the mouse.

METHODS: Male and female mice were subdivided into four age groups: 3, 9, 18, and 24 months. The supraspinatus (SS) and infraspinatus muscles of the RC and the tibialis anterior (TA) muscle of the hindlimb were assessed. Muscle mass, contractile …

Mental Health In The Uk Biobank: A Roadmap To Self-Report Measures And Neuroimaging Correlates, Rosie K Dutt, Kayla Hannon, Ty O Easley, Joseph C Griffis, Wei Zhang, Janine D Bijsterbosch

2020-Current year OA Pubs

The UK Biobank (UKB) is a highly promising dataset for brain biomarker research into population mental health due to its unprecedented sample size and extensive phenotypic, imaging, and biological measurements. In this study, we aimed to provide a shared foundation for UKB neuroimaging research into mental health with a focus on anxiety and depression. We compared UKB self-report measures and revealed important timing effects between scan acquisition and separate online acquisition of some mental health measures. To overcome these timing effects, we introduced and validated the Recent Depressive Symptoms (RDS-4) score which we recommend for state-dependent and longitudinal research in …

Importance Of The Intersection Of Age And Sex To Understand Variation In Incidence And Survival For Primary Malignant Gliomas, Gi-Ming Wang, Gino Cioffi, Nirav Patil, Kristin A Waite, Robert Lanese, Quinn T Ostrom, Carol Kruchko, Michael E Berens, James R Connor, Justin D Lathia, Joshua B Rubin, Jill S Barnholtz-Sloan

2020-Current year OA Pubs

BACKGROUND: Gliomas are the most common type of malignant brain and other CNS tumors, accounting for 80.8% of malignant primary brain and CNS tumors. They cause significant morbidity and mortality. This study investigates the intersection between age and sex to better understand variation of incidence and survival for glioma in the United States.

METHODS: Incidence data from 2000 to 2017 were obtained from CBTRUS, which obtains data from the NPCR and SEER, and survival data from the CDC's NPCR. Age-adjusted incidence rate ratios (IRR) per 100 000 were generated to compare male-to-female incidence by age group. Cox proportional hazard models …

Fractality Of Tics As A Quantitative Assessment Tool For Tourette Syndrome, Payton Beeler, Nicholas O Jensen, Soyoung Kim, Amy Robichaux-Viehoever, Bradley L Schlaggar, Deanna J Greene, Kevin J. Black, Rajan K Chakrabarty

2020-Current year OA Pubs

Tics manifest as brief, purposeless and unintentional movements or noises that, for many individuals, can be suppressed temporarily with effort. Previous work has hypothesized that the chaotic temporal nature of tics could possess an inherent fractality, that is, have neighbour-to-neighbour correlation at all levels of timescale. However, demonstrating this phenomenon has eluded researchers for more than two decades, primarily because of the challenges associated with estimating the scale-invariant, power law exponent-called the fractal dimension

Racial And Ethnic Minorities Have A Lower Prevalence Of Airflow Obstruction Than Non-Hispanic Whites, Akshay Sood, Hans Petersen, Congjian Liu, Orrin Myers, Xin Wang Shore, Bobbi A Gore, Rodrigo Vazquez-Guillamet, Linda S Cook, Paula Meek, Yohannes Tesfaigzi

Open Access Publications

Racial and ethnic disparities in chronic obstructive pulmonary disease (COPD) are not well-studied. Our objective was to examine differences in limited COPD-related outcomes between three minority groups-African Americans (AAs), Hispanics, and American Indians (AIs) versus non-Hispanic Whites (NHWs), as the referent group, in separate cohorts. Separate cross-sectional evaluations were performed of three US-based cohorts of subjects at risk for COPD: COPDGene Study with 6,884 NHW and 3,416 AA smokers; Lovelace Smokers' Cohort with 1,598 NHW and 378 Hispanic smokers; and Mining Dust Exposure in the United States Cohort with 2,115 NHW, 2,682 Hispanic, and 2,467 AI miners. Prebronchodilator spirometry tests …

Analysis Of Non-Relapsed And Relapsed Adult Type Granulosa Cell Tumors Suggests Stable Transcriptomes During Tumor Progression, Noora Andersson, Ulla-Maija Haltia, Anniina Färkkilä, Swee Chong Wong, Katja Eloranta, David B Wilson, Leila Unkila-Kallio, Marjut Pihlajoki, Antti Kyrönlahti, Markku Heikinheimo

2020-Current year OA Pubs

Adult-type granulosa cell tumor (AGCT) is a rare ovarian malignancy characterized by slow growth and hormonal activity. The prognosis of AGCT is generally favorable, but one-third of patients with low-stage disease experience a late relapse, and over half of them die of AGCT. To identify markers that would distinguish patients at risk for relapse, we performed Lexogen QuantSeq 3' mRNA sequencing on formalin-fixed paraffin-embedded, archival AGCT tissue samples tested positive for the pathognomonic Forkhead Box L2 (

Computational Genomics In The Era Of Precision Medicine: Applications To Variant Analysis And Gene Therapy, Yung-Chun Wang, Julie Choi, Shujuan Zhao, Mariam Khanfar, Kuangying Yang, Po-Ying Fu, Max Wrubel, Xiaobing Yu, Sheng Chih Jin, Et Al

Open Access Publications

Rapid methodological advances in statistical and computational genomics have enabled researchers to better identify and interpret both rare and common variants responsible for complex human diseases. As we continue to see an expansion of these advances in the field, it is now imperative for researchers to understand the resources and methodologies available for various data types and study designs. In this review, we provide an overview of recent methods for identifying rare and common variants and understanding their roles in disease etiology. Additionally, we discuss the strategy, challenge, and promise of gene therapy. As computational and statistical approaches continue to …

Importance Of Csf-Based Aβ Clearance With Age In Humans Increases With Declining Efficacy Of Blood-Brain Barrier/Proteolytic Pathways, Donald L Elbert, Bruce W Patterson, Brendan P Lucey, Tammie L S Benzinger, Randall J Bateman

Open Access Publications

The kinetics of amyloid beta turnover within human brain is still poorly understood. We previously found a dramatic decline in the turnover of Aβ peptides in normal aging. It was not known if brain interstitial fluid/cerebrospinal fluid (ISF/CSF) fluid exchange, CSF turnover, blood-brain barrier function or proteolysis were affected by aging or the presence of β amyloid plaques. Here, we describe a non-steady state physiological model developed to decouple CSF fluid transport from other processes. Kinetic parameters were estimated using: (1) MRI-derived brain volumes, (2) stable isotope labeling kinetics (SILK) of amyloid-β peptide (Aβ), and (3) lumbar CSF Aβ concentration …

Whole-Exome Analysis Of Adolescents With Low Vwf And Heavy Menstrual Bleeding Identifies Novel Genetic Associations, Brooke Sadler, Christina A Gurnett, Jorge Di Paola, Et Al

Open Access Publications

Adolescents with low von Willebrand factor (VWF) levels and heavy menstrual bleeding (HMB) experience significant morbidity. There is a need to better characterize these patients genetically and improve our understanding of the pathophysiology of bleeding. We performed whole-exome sequencing on 86 postmenarchal patients diagnosed with low VWF levels (30-50 IU/dL) and HMB and compared them with 660 in-house controls. We compared the number of rare stop-gain/stop-loss and rare ClinVar "pathogenic" variants between cases and controls, as well as performed gene burden and gene-set burden analyses. We found an enrichment in cases of rare stop-gain/stop-loss variants in genes involved in bleeding …

Longitudinal Study After Sputnik V Vaccination Shows Durable Sars-Cov-2 Neutralizing Antibodies And Reduced Viral Variant Escape To Neutralization Over Time, María M Gonzalez Lopez Ledesma, Paul W Rothlauf, Zhuoming Liu, Louis-Marie Bloyet, Marjorie Cornejo Pontelli, Et Al

Open Access Publications

Recent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we examined longitudinal antibody responses and viral neutralizing capacity to the B.1 lineage virus (Wuhan related), to variants of concern (VOC; Alpha, Beta, Gamma, and Delta), and to a local variant of interest (VOI; Lambda) in volunteers receiving the Sputnik V vaccine in Argentina. Longitudinal serum samples (

Inhibiting Mycobacterium Abscessus Cell Wall Synthesis: Using A Novel Diazabicyclooctane Β-Lactamase Inhibitor To Augment Β-Lactam Action, Khalid M Dousa, David C Nguyen, Sebastian G Kurz, Magdalena A Taracila, Christopher R Bethel, William Schinabeck, Barry N Kreiswirth, Sheldon T Brown, W Henry Boom, Richard S Hotchkiss, Kenneth E Remy, Frank J Jacono, Charles L Daley, Steven M Holland, Alita A Miller, Robert A Bonomo

Open Access Publications

Mycobacterium abscessus (

Steroid-Sensitive Nephrotic Syndrome Candidate Gene Clvs1 Regulates Podocyte Oxidative Stress And Endocytosis, Brandon M. Lane, Andrew F. Malone, Et Al.

2020-Current year OA Pubs

We performed next-generation sequencing in patients with familial steroid-sensitive nephrotic syndrome (SSNS) and identified a homozygous segregating variant (p.H310Y) in the gene encoding clavesin-1 (CLVS1) in a consanguineous family with 3 affected individuals. Knockdown of the clavesin gene in zebrafish (clvs2) produced edema phenotypes due to disruption of podocyte structure and loss of glomerular filtration barrier integrity that could be rescued by WT CLVS1 but not the p.H310Y variant. Analysis of cultured human podocytes with CRISPR/Cas9-mediated CLVS1 knockout or homozygous H310Y knockin revealed deficits in clathrin-mediated endocytosis and increased susceptibility to apoptosis that could be rescued with corticosteroid treatment, mimicking …

Bicyclic Azetidines Target Acute And Chronic Stages Of Toxoplasma Gondii By Inhibiting Parasite Phenylalanyl T-Rna Synthetase, Joshua B Radke, Bruno Melillo, Payal Mittal, Manmohan Sharma, Amit Sharma, Yong Fu, Taher Uddin, Arthur Gonse, Eamon Comer, Stuart L Schreiber, Anil K Gupta, Arnab K Chatterjee, L David Sibley

Open Access Publications

Toxoplasma gondii commonly infects humans and while most infections are controlled by the immune response, currently approved drugs are not capable of clearing chronic infection in humans. Hence, approximately one third of the world's human population is at risk of reactivation, potentially leading to severe sequelae. To identify new candidates for treating chronic infection, we investigated a series of compounds derived from diversity-oriented synthesis. Bicyclic azetidines are potent low nanomolar inhibitors of phenylalanine tRNA synthetase (PheRS) in T. gondii, with excellent selectivity. Biochemical and genetic studies validate PheRS as the primary target of bicyclic azetidines in T. gondii, providing a …

Neural Signatures Of Data-Driven Psychopathology Dimensions At The Transition To Adolescence, Amirhossein Modabbernia, Giorgia Michelini, Abraham Reichenberg, Roman Kotov, Deanna Barch, Sophia Frangou

Open Access Publications

BACKGROUND: One of the challenges in human neuroscience is to uncover associations between brain organization and psychopathology in order to better understand the biological underpinnings of mental disorders. Here, we aimed to characterize the neural correlates of psychopathology dimensions obtained using two conceptually different data-driven approaches.

METHODS: Dimensions of psychopathology that were either maximally dissociable or correlated were respectively extracted by independent component analysis (ICA) and exploratory factor analysis (EFA) applied to the Childhood Behavior Checklist items from 9- to 10-year-olds (n = 9983; 47.8% female, 50.8% white) participating in the Adolescent Brain Cognitive Development study. The patterns of brain …

Grandi Byen-Supporting Child Growth And Development Through Integrated, Responsive Parenting, Nutrition And Hygiene: Study Protocol For A Randomized Controlled Trial, Patricia L Kohl, Emmanuel A Gyimah, Jenna Diaz, F Matthew Kuhlmann, Sherlie Jean-Louis Dulience, Fithi Embaye, Derek S Brown, Shenyang Guo, Joan L Luby, Jennifer L Nicholas, Jay Turner, Melissa Chapnick, Joseline Marhone Pierre, Jacques Boncy, Rony St Fleur, Maureen M Black, Lora L Iannotti

2020-Current year OA Pubs

BACKGROUND: Poor child growth and development outcomes stem from complex relationships encompassing biological, behavioral, social, and environmental conditions. However, there is a dearth of research on integrated approaches targeting these interwoven factors. The Grandi Byen study seeks to fill this research gap through a three-arm longitudinal randomized controlled trial which will evaluate the impact of an integrated nutrition, responsive parenting, and WASH (water, sanitation and hygiene) intervention on holistic child growth and development.

METHODS: We will recruit 600 mother-infant dyads living in Cap-Haitien, Haiti and randomize them equally into one of the following groups: 1) standard well-baby care; 2) nutritional …

Enrichment Of The Exocytosis Protein Stx4 In Skeletal Muscle Remediates Peripheral Insulin Resistance And Alters Mitochondrial Dynamics Via Drp1, Karla E Merz, Jinhee Hwang, Chunxue Zhou, Rajakrishnan Veluthakal, Erika M Mccown, Angelica Hamilton, Eunjin Oh, Wenting Dai, Patrick T Fueger, Lei Jiang, Janice M Huss, Debbie C Thurmond

Open Access Publications

Mitochondrial dysfunction is implicated in skeletal muscle insulin resistance. Syntaxin 4 (STX4) levels are reduced in human diabetic skeletal muscle, and global transgenic enrichment of STX4 expression improves insulin sensitivity in mice. Here, we show that transgenic skeletal muscle-specific STX4 enrichment (skmSTX4tg) in mice reverses established insulin resistance and improves mitochondrial function in the context of diabetogenic stress. Specifically, skmSTX4tg reversed insulin resistance caused by high-fat diet (HFD) without altering body weight or food consumption. Electron microscopy of wild-type mouse muscle revealed STX4 localisation at or proximal to the mitochondrial membrane. STX4 enrichment prevented HFD-induced mitochondrial fragmentation and dysfunction through …

The Immunoregulatory Landscape Of Human Tuberculosis Granulomas, Erin F. Mccaffrey, Shabaana A. Khader, Et Al

Open Access Publications

No abstract provided.

The Gut Microbiota Of Chickens In A Commercial Farm Treated With A Salmonella Phage Cocktail, Viviana Clavijo, Tatiana Morales, Martha Josefina Vives-Flores, Alejandro Reyes Muñoz

Open Access Publications

The microbiota in broiler chicken intestines affects the animals' health, metabolism, and immunity both positively and negatively. Accordingly, it has a significant impact on animal productivity. Phages, host-specific parasites of bacterial cells, are a promising antimicrobial alternative that selectively target pathogens without disturbing the microbiota. The purpose of this study is to further characterize the commensal microbial community at production scale in broiler chickens treated with a Salmonella phage treatment. We evaluated the cecal microbiota of broilers reared in a commercial farming system where a phage cocktail against Salmonella, SalmoFree was supplied to animals. To do so, two field trials …

Comparative Genomics Of Bacteroides Fragilis Group Isolates Reveals Species-Dependent Resistance Mechanisms And Validates Clinical Tools For Resistance Prediction, Miranda J Wallace, Sophonie Jean, Meghan A Wallace, Carey-Ann D Burnham, Gautam Dantas

Open Access Publications

Bacteroides fragilis group (BFG) are the most frequently recovered anaerobic bacteria from human infections, and resistance to frontline antibiotics is emerging. In the absence of routine antimicrobial susceptibility testing (AST) for BFG in most clinical settings, we assessed the utility of clinical and modern genomics tools to determine BFG species-level identification and resistance patterns. A total of 174 BFG clinical isolates supplemented with 20 archived carbapenem-resistant B. fragilis

Jib-04 Has Broad-Spectrum Antiviral Activity And Inhibits Sars-Cov-2 Replication And Coronavirus Pathogenesis, Juhee Son, Shimeng Huang, Qiru Zeng, Traci L Bricker, James Brett Case, Ruochen Zang, Zhuoming Liu, Tamarand L Darling, Jian Xu, Houda H Harastani, Maria Florencia Gomez Castro, Hinissan P Kohio, Gaopeng Hou, Paul W Rothlauf, Adam L Bailey, Steven L Brody, Sean P J Whelan, Michael S Diamond, Adrianus C M Boon, Siyuan Ding, Et Al

Open Access Publications

Pathogenic coronaviruses are a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified small-molecule inhibitors that potently block the replication of severe acute respiratory syndrome virus 2 (SARS-CoV-2). Among them, JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with a 50% effective concentration of 695 nM, with a specificity index of greater than 1,000. JIB-04 showed

Spotlight On Nociceptin/Orphanin Fq Receptor In The Treatment Of Pain, Amal El Daibani, Tao Che

Open Access Publications

No abstract provided.

Reevaluation Of The Role Of Lip-1 As An Erk/Mpk-1 Dual Specificity Phosphatase In The C. Elegans Germline, Debabrata Das, Jacob Seemann, David Greenstein, Tim Schedl, Swathi Arur

Open Access Publications

The fidelity of a signaling pathway depends on its tight regulation in space and time. Extracellular signal-regulated kinase (ERK) controls wide-ranging cellular processes to promote organismal development and tissue homeostasis. ERK activation depends on a reversible dual phosphorylation on the TEY motif in its active site by ERK kinase (MEK) and dephosphorylation by DUSPs (dual specificity phosphatases). LIP-1, a DUSP6/7 homolog, was proposed to function as an ERK (MPK-1) DUSP in the