Public Release:  JCI early table of contents for Oct. 15, 2013

Journal of Clinical Investigation

Sound preconditioning prevents ototoxic drug-induced hearing loss in mice

The death of sensory hair cells in the ear results in irreversible hearing loss. Several classes of drugs, including aminoglycoside antibiotics and chemotherapy drugs are known to kill hair cells; however, in many cases the benefit of using the drug outweighs the potential for hearing loss. Previous research has shown that a class of proteins induced in response to cell stress, the heat shock proteins (HSPs), can protect against sensory hair cell death in response to ototoxic drugs. Despite understanding how HSPs protect the hair cells of the inner ear, there are no current therapies to induce expression of or deliver HSP directly to the inner ear. In this issue of the Journal of Clinical Investigation, Lisa Cunningham and colleagues at the National Institutes of Health developed a sound preconditioning protocol in mice that did not damage hearing, but induced HSP expression in the ear. They found that sound conditioning prior to treatment with ototoxic drugs, protected mice from drug-induced hearing loss. Furthermore, sound preconditioning resulted in increased expression of HSPs in the inner ear. Together, these data indicate that sound therapy may protect hearing in patients that require treatment with ototoxic drugs.

TITLE: Sound preconditioning therapy inhibits ototoxic hearing loss in mice

AUTHOR CONTACT: Lisa L. Cunningham
NIH/NIDCD, Rockville, MD, USA
Phone: 3014432766; E-mail:

View this article at:

Bone loss associated with increased production of ROS

Bone is constantly being broken down and remodeled. Osteoporosis results when bone resorption outpaces bone regeneration. Production of reactive oxygen species, a form of oxidative stress, has been predicted to promote bone loss, but a source of reactive oxygen is unknown. In this issue of the Journal of Clinical Investigation, Katrin Schröder and colleagues at Goethe-University identify a relationship between NADPH oxidase 4 (NOX4), an enzyme that promotes reactive oxygen species formation, and bone resorption. In a mouse model of osteoporosis, genetic disruption or drug-induced loss of NOX4 protected the mice from bone loss. Additionally, the authors identify a small nuclear polymorphism in NOX4 in human patients that associated with increased bone turnover. Together, these data suggest treatments targeting NOX4 activity may benefit osteoporosis patients.

TITLE: NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis

AUTHOR CONTACT: Katrin Schröder
Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt, UNK, DEU
Phone: 004969630183660; E-mail:

View this article at:


TITLE: Type III TGF-β receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma

Duke University, Durham, NC, USA
Phone: (919) 668-1352; Fax: (919) 681-6906; E-mail:

View this article at:

TITLE: Induction of myelodysplasia by myeloid-derived suppressor cells

Moffitt Cancer Center, Tampa, FL, USA
Phone: 813-745-3934; Fax: 813-745-7264; E-mail:

View this article at:

TITLE: Hirschsprung-like disease is exacerbated by reduced de novo GMP synthesis

AUTHOR CONTACT: Robert Heuckeroth
Washington University School of Medicine, St. Louis, MO, USA
Phone: 314-286-2853; Fax: 314-286-2893; E-mail:

View this article at:

TITLE: Allogeneic T-cell responses are regulated by a specific miRNA-mRNA network

University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA
Phone: 734-647-5954; Fax: 734-647-9647; E-mail:

View this article at:

TITLE: Chronic itch development in sensory neurons requires BRAF signaling pathways

Washington University, St. Louis, MO, USA
Phone: (314) 747-5093; E-mail:

View this article at:

TITLE: A recurrent dominant-negative E47 mutation causes agammaglobulinemia and BCR- B-cells

AUTHOR CONTACT: Mary Ellen Conley
LeBonheur Children's Hospital, Memphis, TN, USA
Phone: 901-287-4657; Fax: 901-287-5036; E-mail:

View this article at:


Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.