10 Works

Activity-based protein profiling for target identification of JCP276 in Mycobacterium tuberculosis

Brett Babin
The increasing incidence of antibiotic-resistant Mycobacterium tuberculosis infections is a growing global health threat necessitating the development of new antibiotics. Serine hydrolases (SHs) are a promising class of targets because of their importance for the synthesis of the mycobacterial cell envelope. We screened a library of small molecules containing serine-reactive electrophiles and identified a series of narrow spectrum inhibitors of M. tuberculous growth. Using these lead molecules we performed competitive activity-based protein profiling and identified...

Toxplasma gondii wild-type vs. ASH4 knockout untargeted metabolomics raw data

Brett Babin & Matthew Bogyo
The intracellular protozoan parasite Toxoplasma gondii must scavenge cholesterol and other lipids from the host to facilitate intracellular growth and replication. Enzymes responsible for neutral lipid synthesis have been identified but there is no evidence for enzymes that catalyze lipolysis of cholesterol esters and esterified lipids. Here we characterize several T. gondii serine hydrolases with esterase and thioesterase activities that were previously thought to be depalmitoylating enzymes. We find they do not cleave palmitoyl thiol...

A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids

Themistocles Assimes & Min A Jhun
We examined the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identified 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observed a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with...

Structure-activity mapping of ARHGAP36 reveals regulatory roles for its GAP homology and C-terminal domains

Patricia R. Nano, Taylor K. Johnson, Takamasa Kudo, Nancie A. Mooney, Jun Ni, Janos Demeter, Peter K. Jackson & James K. Chen
ARHGAP36 is an atypical Rho GTPase-activating protein (GAP) family member that drives both spinal cord development and tumorigenesis, acting in part through an N-terminal motif that suppresses protein kinase A and activates Gli transcription factors. ARHGAP36 also contains isoform-specific N-terminal sequences, a central GAP-like module, and a unique C-terminal domain, and the functions of these regions remain unknown. Here we have mapped the ARHGAP36 structure-activity landscape using a deep sequencing-based mutagenesis screen and truncation mutant...

Lipidomic profiling of Mycobacterium tuberculosis treated with JCP276, BMB034, or THL

Brett Babin
The increasing incidence of antibiotic-resistant Mycobacterium tuberculosis infections is a growing global health threat necessitating the development of new antibiotics. Serine hydrolases (SHs) are a promising class of targets because of their importance for the synthesis of the mycobacterial cell envelope. We screened a library of small molecules containing serine-reactive electrophiles and identified a series of narrow spectrum inhibitors of M. tuberculous growth. Using these lead molecules we performed competitive activity-based protein profiling and identified...

Integrated trajectories of the maternal metabolome, proteome, and immunome predict labor onset

Ina Stelzer, Mohammad Sajjad Ghaemi, Xiaoyuan Han, Kazuo Ando, Julien Hedou, Martin Angst, Nima Aghaeepour, Brice Gaudilliere, Dorien Feyaerts, Laura S. Peterson, Kristen K. Rumer, Eileen S. Tsai, Edward A. Ganio, Dyani K. Gaudillière, Amy S. Tsai, Benjamin Choisy, Lea P. Gaigne, Franck Verdonk, Danielle Jacobsen, Sonia Gavasso, Gavin M. Traber, Mathew Ellenberger, Natalie Stanley, Martin Becker, Anthony Culos … & Kévin Contrepois
Estimating the time of delivery is of high clinical importance because pre- and postterm deviations are associated with complications for the mother and her offspring. However, current estimations are inaccurate. As pregnancy progresses toward labor, major transitions occur in fetomaternal immune, metabolic, and endocrine systems that culminate in birth. The comprehensive characterization of maternal biology that precedes labor is key to understanding these physiological transitions and identifying predictive biomarkers of delivery. Here, a longitudinal study...

Imaging dataset for positron emission microscopy of patient-derived tumor organoids

Syamantak Khan & Guillem Pratx
Here, we present a microscopy method to image 18F-fluorodeoxyglucose and other radiotracers in patient-derived tumor organoids with spatial resolution up to 100-fold better than that of clinical positron emission tomography (PET). When combined with brightfield imaging, this metabolic imaging approach functionally mirrors clinical PET/CT scans and provides a quantitative readout of cell glycolysis other metabolic processes.

The Fairness and Generalizability Assessment Framework

Eliane Röösli, Selen Bozkurt & Tina Hernandez-Boussard
As artificial intelligence makes continuous progress to improve quality of care for some patients by leveraging ever increasing amounts of digital health data, others are left behind. Empirical evaluation studies are required to keep biased AI models from reinforcing systemic health disparities faced by minority populations through dangerous feedback loops. We developed a broadly applicable fairness and generalizability assessment framework and used it to perform a case study on a MIMIC-trained benchmarking model. While open-science...

Land use impacts on parasitic infection: A cross-sectional epidemiological study on the role of irrigated agriculture in schistosome infection in a dammed landscape

Andrea Lund, David Rehkopf, Susanne Sokolow, M. Moustapha Sam, Nicolas Jouanard, Anne-Marie Schacht, Simon Senghor, Assane Fall, Gilles Riveau, Giulio De Leo & David Lopez-Carr
Background: Water resources development promotes agricultural expansion and food security. But are these benefits offset by increased infectious disease risk? Dam construction on the Senegal River in 1986 was followed by agricultural expansion and increased transmission of human schistosomes. Yet the mechanisms linking these processes at the individual and household levels remain unclear. We investigated the association between household land use and schistosome infection in children. Methods: We analyzed cross-sectional household survey data (n =...

Impact of the surgical approach to thymectomy upon complete stable remission rates in myasthenia gravis: a meta-analysis

Andrea Paola Solis Pazmino, Ioana Baiu, Eddy Lincango, Winston Trope, Larry Prokop, Oscar Ponce & Joseph Shrager
Objectives: To determine whether any of the available operative techniques confer variable chances for complete stable remission (CSR) in myasthenia gravis (MG), we performed a meta-analysis of all comparative studies of surgical approaches. Methods: Meta-analysis of all studies providing comparative data on thymectomy approaches, with CSR reported and minimum 3 years mean follow-up. Results: 12 cohort studies and one randomized clinical trial, containing 1598 patients, met entry criteria. At 3 years, CSR from MG was...

Registration Year

  • 2021
    10

Resource Types

  • Dataset
    9
  • Software
    1

Affiliations

  • Stanford University School of Medicine
    10
  • Society for Maternal-Fetal Medicine
    1
  • Korean Association of Maxillofacial Plastic and Reconstructive Surgery
    1
  • Stanford University
    1
  • Espoir pour la Sante
    1
  • Swiss Federal Institute of Technology in Lausanne
    1
  • University of California, Santa Barbara
    1
  • Stanford Medicine
    1
  • Mayo Clinic
    1
  • Palo Alto University
    1