16 Works

Data from: Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis

James F. Howard, Vera Bril, Ted M. Burns, Renato Mantegazza, Malgorzata Bilinska, Andrzej Szczudlik, Said Beydoun, Francisco Javier Rodriguez De Rivera Garrido, Fredrik Piehl, Mariarosa Rottoli, Philip Van Damme, Tuan Vu, Amelia Evoli, Miriam Freimer, Tahseen Mozaffar, E. Sally Ward, Torsten Dreier, Peter Ulrichts, Katrien Verschueren, Antonio Guglietta, Hans De Haard, Nicolas Leupin & Jan J. G. M. Verschuuren
Objective: To investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment. Methods: A phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or...

Data from: A GWAS approach identifies Dapp1 as a determinant of air pollution-induced airway hyperreactivity

Hooman Allayee
Asthma is a chronic inflammatory disease of the airways with contributions from genes, environmental exposures, and their interactions. While genome-wide association studies (GWAS) in humans have identified ~200 susceptibility loci, the genetic factors that modulate risk of asthma through gene-environment (GxE) interactions remain poorly understood. Using the Hybrid Mouse Diversity Panel (HMDP), we sought to identify the genetic determinants of airway hyperreactivity (AHR) in response to diesel exhaust particles (DEP), a model traffic-related air pollutant....

Data from: Reprogramming the antigen specificity of B cells using genome-editing technologies

James E. Voss, Alicia Gonzalez-Martin, Raiees Andrabi, Roberta P. Fuller, Ben Murrell, Laura E. McCoy, Katelyn Porter, Deli Huang, Wenjuan Li, Devin Sok, Khoa Le, Bryan Briney, Morgan Chateau, Geoffrey Rogers, Lars Hangartner, Ann J. Feeney, David Nemazee, Paula Cannon & Dennis R. Burton
We have developed a method to introduce novel paratopes into the human antibody repertoire by modifying the immunoglobulin (Ig) genes of mature B cells directly using genome editing technologies. We used CRISPR-Cas9 in a homology directed repair strategy, to replace the heavy chain (HC) variable region in B cell lines with that from an HIV broadly neutralizing antibody, PG9. Our strategy is designed to function in cells that have undergone VDJ recombination using any combination...

Data from: A new ophiocistioid with soft-tissue preservation from the Silurian Herefordshire Lagerstätte, and the evolution of the holothurian body plan

Imran Rahman, Jeffrey Thompson, Derek Briggs, David Siveter, Derek Siveter & Mark Sutton
Reconstructing the evolutionary assembly of animal body plans is challenging when there are large morphological gaps between extant sister taxa, as in the case of echinozoans (echinoids and holothurians). However, the inclusion of extinct taxa can help bridge these gaps. Here we describe a new species of echinozoan, Sollasina cthulhu, from the Silurian Herefordshire Lagerstätte, UK. S. cthulhu belongs to the ophiocistioids, an extinct group that shares characters with both echinoids and holothurians. Using physical-optical...

Data from: Mid-Cretaceous amber inclusions reveal morphogenesis of extinct rachis-dominated feathers

Nathan Carroll, Luis M. Chiappe & David J. Bottjer
We describe three-dimensionally preserved feathers in mid-Cretaceous Burmese amber that share macro-morphological similarities (e.g., proportionally wide rachis with a “medial stripe”) with lithic, two-dimensionally preserved rachis-dominated feathers. These feathers in amber reveal a unique ventrally concave and dorsoventrally thin rachis, and a dorsal groove (sometimes pigmented) that we identify as the “medial stripe” visible in many rachis-dominated rectrices of Mesozoic birds. The distally pennaceous portion of these feathers shows differentiated proximal and distal barbules, the...

Data from: Computed tomography shows high fracture prevalence among physically active forager-horticulturalists with high fertility

Jonathan Stieglitz, Benjamin C. Trumble, Study Team HORUS, Caleb Finch, Dong Li, Matthew J. Budoff, Hillard Kaplan & Michael Gurven
Modern humans have more fragile skeletons than other hominins, which may result from physical inactivity. Here we test whether reproductive effort also compromises bone strength, by measuring using computed tomography thoracic vertebral bone mineral density (BMD) and fracture prevalence among physically active Tsimane forager-horticulturalists. Earlier onset of reproduction and shorter interbirth intervals are associated with reduced BMD for women. Tsimane BMD is lower versus Americans, but only for women, contrary to simple predictions relying on...

Osteology of the late Triassic bipedal archosaur Poposaurus gracilis (Archosauria: Pseudosuchia) from Western North America

Emma R. Schachner, Randall B. Irmis, Adam K. Huttenlocker, Kent Sanders, Robert L. Cieri & Sterling J. Nesbitt
Poposaurus gracilis is a bipedal pseudosuchian archosaur that has been poorly understood since the discovery of the holotype fragmentary partial postcranial skeleton in 1915. Poposaurus. gracilis is a member of Poposauroidea, an unusually morphologically divergent clade of pseudosuchians containing taxa that are bipedal, quadrupedal, toothed, edentulous, and some individuals with elongated thoracic neural spines (i.e., sails). In 2003, a well preserved, fully articulated, and nearly complete postcranial skeleton of P. gracilis was discovered with some...

Data from: FOXP2 exhibits neuron class specific expression, but is not required for multiple aspects of cortical histogenesis

Ryan J. Kast, Alexandra L. Lanjewar, Colton D. Smith & Pat Levitt
The expression patterns of the transcription factor FOXP2 in the developing mammalian forebrain have been described, and some studies have tested the role of this protein in the development and function of specific forebrain circuits by diverse methods and in multiple species. Clinically, mutations in FOXP2 are associated with severe developmental speech disturbances, and molecular studies indicate that impairment of Foxp2 may lead to dysregulation of genes involved in forebrain histogenesis. Here, anatomical and molecular...

Dataset S1 - P-wave velocity model of Long Beach, CA.

P-wave velocity model of Long Beach, California. The node spacing of the velocity model is 70 m.

Data from: GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis through miR-126

, Xin Geng, YenChun Ho, Boksik Cha, Yuenhee Kim, Jing Ma, Lijuan Chen, Greggory Myers, Sally Camper, Debbie Mustacich, Marlys Witte, Dongwon Choi, Young-Kwon Hong, Hong Chen, Gaurav Varshney, James D Engel, Shusheng Wang, Tae-Hoon Kim, Kim-Chew Lim & Sathish Srinivasan
Mutations in the transcription factor GATA2 cause lymphedema. GATA2 is necessary for the development of lymphatic valves (LVs) and lymphovenous valves (LVVs), and for the patterning of lymphatic vessels. Here, we report that GATA2 is not necessary for valvular endothelial cell (VEC) differentiation. Instead, GATA2 is required for VEC maintenance and morphogenesis. GATA2 is also necessary for the expression of cell junction molecules VE-Cadherin and Claudin5 in lymphatic vessels. We identified miR-126 as a target...

Data from: Polygenic adaptation on height is overestimated due to uncorrected stratification in genome-wide association studies

Mashaal Sohail, Robert M. Maier, Andrea Ganna, Alex Bloemendal, Alicia R. Martin, Michael C. Turchin, Charleston W. K. Chang, Joel Hirschhorn, Mark J. Daly, Nick Patterson, Benjamin Neale, Iain Mathieson, David Reich & Shamil R. Sunyaev
Genetic predictions of height differ among human populations and these differences have been interpreted as evidence of polygenic adaptation. These differences were first detected using SNPs genome-wide significantly associated with height, and shown to grow stronger when large numbers of sub-significant SNPs were included, leading to excitement about the prospect of analyzing large fractions of the genome to detect polygenic adaptation for multiple traits. Previous studies of height have been based on SNP effect size...

Data from: Differential responses to ocean acidification between populations of Balanophyllia elegans corals from high and low upwelling environments

Joanna S. Griffiths, Francis T. Pan & Morgan W. Kelly
Ocean acidification (OA), the global decrease in surface water pH from absorption of anthropogenic CO2, may put many marine taxa at risk. However, populations that experience extreme localized conditions, and are adapted to these conditions predicted in the global ocean in 2100, may be more tolerant to future OA. By identifying locally adapted populations, researchers can examine the mechanisms used to cope with decreasing pH. One oceanographic process that influences pH, is wind driven upwelling....

Data from: Dynamic relocalization of replication origins by Fkh1 requires execution of DDK function and Cdc45 loading at origins

Haiyang Zhang, Meghan V Petrie, Yiwei He, Jared M Peace, Irene E Chiolo & Oscar M Aparicio
Chromosomal DNA elements are organized into spatial domains within the eukaryotic nucleus. For example, sites actively undergoing DNA replication, high-level transcription, and repair of double-strand breaks coalesce into foci, although the significance and mechanisms giving rise to these dynamic structures are poorly understood. In S. cerevisiae, replication origins exhibit characteristic subnuclear localizations prior to S phase that anticipate their initiation timing and/or efficiency during S phase: origins found within the nuclear interior in G1 phase...

Data from: A parapithecid stem anthropoid of African origin in the Paleogene of South America

Erik Seiffert, Marcelo Tejedor, John Fleagle, Nelson Novo, Fanny Cornejo, Mariano Bond, Dorien De Vries & Kenneth Campbell
Phylogenetic evidence suggests that platyrrhine (or New World) monkeys and caviomorph rodents of the Western Hemisphere derive from source groups from the Eocene of Afro-Arabia, a landmass that was ~1500 to 2000 kilometers east of South America during the late Paleogene. Here, we report evidence for a third mammalian lineage of African origin in the Paleogene of South America—a newly discovered genus and species of parapithecid anthropoid primate from Santa Rosa in Amazonian Perú. Bayesian...

Classification of Type 2 Diabetes Genetic Variants and a Novel Genetic Risk Score Association with Insulin Clearance

Mark Goodarzi, Nicholette D Palmer, Jinrui Cui, Xiuqing Guo, Yii-Der I Chen, Kent D Taylor, Leslie J Raffel, Lynne E Wagenknecht, Thomas A Buchanan, Willa A Hsueh & Jerome I Rotter
Abstract Context Genome-wide association studies have identified >450 single nucleotide polymorphisms (SNPs) for type 2 diabetes (T2D). Objective To facilitate use of these SNPs in future genetic risk score (GRS)-based analyses, we aimed to classify the SNPs based on physiology. We also sought to validate GRS associations with insulin-related traits in deeply-phenotyped Mexican Americans. Design, Setting, and Participants 457 T2D SNPs from the literature were assigned physiologic function based on association studies and cluster analyses....

Data from: Elovanoids counteract oligomeric β-Amyloid-induced gene expression and protect photoreceptors

Nicolas Bazan, Khanh Do, Marie-Audrey Kautzmann, Bokkyoo Jun, William Gordon, Robert Nshimiyimana, Rong Yang & Nicos Petasis
The onset of neurodegenerative diseases activates inflammation that leads to progressive neuronal cell death and impairments in cognition (Alzheimer’s disease, AD) and sight (age-related macular degeneration, AMD). How neuroinflammation can be counteracted is not known. In AMD, amyloid β-peptide (Aβ) accumulates in subretinal drusen. In the 5xFAD retina, we found early functional deficiencies (ERG) without photoreceptor cell (PRC) death and identified early insufficiency in biosynthetic pathways of pro-homeostatic/neuroprotective mediators, neuroprotectin D1 (NPD1) and elovanoids (ELVs)....

Registration Year

  • 2019

Resource Types

  • Dataset


  • University of Southern California
  • Natural History Museum of Los Angeles County
  • Autonomous University of Madrid
  • Louisiana State University Health Sciences Center New Orleans
  • University of California, Irvine
  • Harbor–UCLA Medical Center
  • Emory University School of Medicine
  • University of Pennsylvania
  • The Ohio State University Wexner Medical Center
  • Boston Children's Hospital