Identification of a broadly neutralizing HIV-1 antibody in a lupus patient
Broadly neutralizing antibodies (BnAbs) recognize conserved epitopes, representing a promising strategy for targeting rapidly mutating viruses. BnAbs display a unique set of characteristics that suggest their development may be limited by immune tolerance. Interestingly, the HIV-1 infection frequency is disproportionately low among patients with the autoimmune disease lupus. In this issue of the Journal of Clinical Investigation, Mattia Bonsignori and colleagues at Duke University identified an HIV-1-infected individual that developed lupus. The patient exhibited low viral load in absence of HIV-1 controlling HLA types, and serum from this patient had broad HIV-1 neutralizing capacity. Bonsignori and colleagues isolated B cells from the patient that produced a BnAb that targeted both the HIV-1 envelope and human antigens, such as dsDNA, supporting the hypothesis that lax immune control allows for maturation and production of BnAbs.
TITLE: An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1
AUTHOR CONTACT: Mattia BonsignoriDuke University Medical Center, Durham, NC, USAPhone: 9196819739; Fax: 9196845230; E-mail: mattia.bonsignori@duke.edu
View this article at: http://www.jci.org/articles/view/73441
Evaluating disease-associated protein turnover kinetics
Dysfunctional protein turnover has been linked to human disorders, including cardiac diseases; however, methods to evaluate the temporal dynamics of multiple proteins in vivo are lacking. In this issue of the Journal of Clinical Investigation, Peipei Ping and colleagues at the University of California Los Angeles developed a workflow that integrates deuterium oxide labeling, mass spectrometry, and computational methods to examine in vivo protein turnover kinetics. Applying their system to a mouse model of isoproterenol-induced cardiac hypertrophy and remodeling, they were able to trace the individual half-life of ~3000 proteins during disease development. The results revealed previously unknown alterations in the temporal regulation of proteins involved in calcium signaling, metabolism, proteostasis, and mitochondrial dynamics. The authors were also able to translate their workflow to humans, and quantified the half-life of ~500 plasma proteins in healthy adults. The workflow requires as little as one biopsy sample, suggesting it can be applied to evaluate protein turnover changes in a range of human diseases.
TITLE: Protein kinetic signatures of the remodeling heart following isoproterenol stimulation
AUTHOR CONTACT: Peipei PingUCLA, Los Angeles, CA, USAPhone: (310) 267-5624; Fax: (310) 267-5623; E-mail: pping@mednet.ucla.edu
View this article at: http://www.jci.org/articles/view/73787
CLINICAL MEDICINE
TITLE: Transport properties of pancreatic cancer describe gemcitabine delivery and response
AUTHOR CONTACT: Jason B. FlemingM.D. Anderson Cancer Center, Houston, TX, USAPhone: 713.745.0890; Fax: 713.745.4426; E-mail: jbflemin@mdanderson.org
View this article at: http://www.jci.org/articles/view/73455
HEMATOLOGY
TITLE: HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers
AUTHOR CONTACT: Swee Lay TheinKing's College London,, London, UNK, GBRPhone: +44-20-7848 5443; Fax: +44-20-7848 5444; E-mail: sl.thein@kcl.ac.uk
View this article at: http://www.jci.org/articles/view/71520
IMMUNOLOGY
TITLE: iNKT cells require TSC1 for terminal maturation and effector lineage fate decisions
AUTHOR CONTACT: Xiao-Ping ZhongDuke University Medical Center, Durham, NC, USAPhone: 919-681-9450; E-mail: zhong001@mc.duke.edu
View this article at: http://www.jci.org/articles/view/69780
TITLE: Collective nitric oxide production provides tissue-wide immunity during Leishmania infection
AUTHOR CONTACT: Philippe BoussoInstitut Pasteur, Paris, FRAPhone: 33 1 45 68 85 51; E-mail: bousso@pasteur.fr
View this article at: http://www.jci.org/articles/view/72058
NEUROSCIENCE
TITLE: Dominant β-catenin mutations cause intellectual disability with recognizable syndromic features
AUTHOR CONTACT: Valter TucciIstituto Italiano di Tecnologia, Genova, ITAPhone: +3901071781; E-mail: Valter.Tucci@iit.it
View this article at: http://www.jci.org/articles/view/70372
ONCOLOGY
TITLE: CDK4 deficiency promotes genomic instability and enhances Myc-driven lymphomagenesis
AUTHOR CONTACT: Xianghong ZouOhio State University, Columbus, , USAPhone: 614-688-8424; E-mail: zou.32@osu.edu
View this article at: http://www.jci.org/articles/view/63139