JCI early table of contents for Nov. 25, 2013
Predicting nasopharyngeal carcinoma patient response to radiation therapy
Nasopharyngeal carcinoma (NPC) affects cells lining the nasopharynx. The majority of NPC cases can be cured by radiation therapy, however ~20% are resistant to radiation treatment. In this issue of the Journal of Clinical Investigation, Yu-Sun Chang and colleagues at Chang Gung University sought to find a way to predict which individual cases of NPC would be sensitive to radiation therapy. The authors compared the levels of various serum factors between NPC patients that responded to radiation therapy and patients that were resistant to therapy. Patients that did not respond to radiation therapy had higher serum levels of the IL-6 family cytokine leukemia inhibitory factor (LIF), and that LIF levels were predictive of NPC patient response to radiation therapy. The researchers further demonstrated that LIF itself promotes NPC. In the companion commentary, Micah Luftig from the Duke University School of Medicine discusses the implications of LIF as a predictor of NPC resistance to radiation therapy.
TITLE: Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance
AUTHOR CONTACT: Yu-Sun Chang
Chang Gung University, Kwei-shan, Taoyuan, , TWN
Phone: 886-3-211-8800 Ext 5131; Fax: 886-3-211-8683; E-mail: ysc@mail.cgu.edu.tw
View this article at: http://www.jci.org/articles/view/63428?key=191243bd59aa6288820e
ACCOMPANYING COMMENTARY
TITLE: Heavy LIFting: tumor promotion and radioresistance in NPC
AUTHOR CONTACT: Micah Luftig
Duke Univeristy School of Medicine, Durham, NC, USA
Phone: (919) 668-3091; Fax: ; E-mail: micah.luftig@duke.edu
View this article at: http://www.jci.org/articles/view/73416?key=15a7795d9596b6418f40
Circadian clock proteins maintain neuronal cell function
The circadian clock synchronizes the molecular activity of cells to their environment. The "core clock" of the circadian system is made up of a group of proteins that autonomously activate and repress each other. BMAL1, one of the activating core clock proteins, is critical for maintaining circadian rhythm and for controlling oxidative stress, normal aging and cognitive ability. In this issue of the Journal of Clinical Investigation, Erik Musiek and colleagues at Washington University School of Medicine asked whether BMAL1 and the rest of the core clock contribute to the maintenance of healthy neurons. Using Bmal1-deficient mice, the authors found that as these mice aged activated astrocytes began to accumulate, a hallmark of active inflammation and damage. Bmal1-deficient mice also displayed localized degeneration of neuronal cells and a loss of functional connectivity, as measured by blood flow. The researchers found that BMAL1 and the other activating core clock proteins regulate important redox proteins that prevent damage caused by oxidative stress. In an accompanying commentary, Colleen McClung from the University of Pittsburgh noted that the activating circadian core clock proteins could be explored as targets for future therapies for neurodegenerative diseases.
TITLE: Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration
AUTHOR CONTACT: Erik Musiek
Washington University School of Medicine, St. Louis, MO, USA
Phone: 3147470286; E-mail: musieke@neuro.wustl.edu
View this article at: http://www.jci.org/articles/view/70317?key=83efd051820931342863
ACCOMPANYING COMMENTARY
TITLE: Mind your rhythms: an important role for circadian genes in neuroprotection
AUTHOR CONTACT: Colleen McClung
University of Pittsburgh Medical Center, Pittsburgh, PA, USA
Phone: 412-624-5547; Fax: ; E-mail: mcclungca@upmc.edu
View this article at: http://www.jci.org/articles/view/73059?key=bf81e41bcbf25b8e31ca
Identifying targets of autoantibodies
Patients with the autoimmune disease systemic lupus erythematosus (SLE) produce autoantibodies that target can cause damage to multiple organ systems. The host factors that are targeted by autoantibodies produced by SLE patients are not fully understood. In this issue of the Journal of Clinical Investigation, Jordan Price and colleagues at Stanford University developed a microarray to identify cytokines, chemokines, and other circulating proteins as potential targets of the autoantibodies produced by SLE patients. The authors identified several autoantibody targets, and determined that SLE patients with high levels of autoantibodies directed against the B cell activating factor (BAFF) had more severe SLE-associated symptoms. In an accompanying commentary, Maureen Su of the University of North Carolina and Stephanie Sarantopoulos of Duke University discuss how identification of autoantibody targets produced by patients with autoimmune disorders will be informative for diagnosis and therapeutic strategy development.
TITLE: Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus
AUTHOR CONTACT: Jordan Price
Stanford University, Stanford, CA, USA
Phone: 650.724.6743; Fax: ; E-mail: jvp2099@gmail.com
View this article at: http://www.jci.org/articles/view/70231?key=58cb6df2455064a28a39
ACCOMPANYING COMMENTARY
TITLE: BAFF-ling autoantibodies
AUTHOR CONTACT: Maureen A. Su
University of North Carolina, Chapel Hill, Chapel Hill, NC, USA
Phone: 919-597-0777; Fax: 919-843-7588; E-mail: masu@email.unc.edu
View this article at: http://www.jci.org/articles/view/73166?key=fd4f43d99da081cda5a8
Balancing T cell populations
Depending on the signals received, naïve T cells are able to differentiate into mature T cell populations, which play different roles in the immune system. For example, regulatory T cells (Tregs) are important for tamping down the immune response and preventing development of autoimmune disease, while effector T cells promote inflammation. Maintaining the proper balance between Tregs and effector T cells prevents immune dysfunction. In this issue of the Journal of Clinical Investigation, Yun-Cai Lu and colleagues at the La Jolla Institute for Allergy and Immunology investigated the role of the mTOR regulator tuberous sclerosis 1 (TSC1) in maintaining immune homeostasis. Using a mouse model, the authors found that loss of TSC1 in T cells, tipped the balance between Tregs and effector T cells and promoted severe inflammation in a colitis model. In the absence of TSC1, Tregs inappropriately produced proinflammatory cytokines, thereby promoting inflammation and damage responses. In an accompanying commentary, Kai Yang and Hongbo Chi at St. Jude Children's Research Hospital discuss how fine tuning mTOR activity through regulators such as TSC1 may be beneficial for treating autoimmune and inflammatory diseases
TITLE: TSC1 regulates the balance between effector and regulatory T cells
AUTHOR CONTACT: Yun-Cai Liu
La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA
Phone: 858-752-6810; Fax: 858-752-6985; E-mail: yuncail@liai.org
View this article at: http://www.jci.org/articles/view/69751?key=e30edd227923f01ef7e9
ACCOMPANYING COMMENTARY
TITLE: Tuning mTOR activity for immune balance
AUTHOR CONTACT: Hongbo Chi
St. Jude Children's Research Hospital, Memphis, , USA
Phone: 901-595-6282; Fax: ; E-mail: Hongbo.Chi@STJUDE.ORG
View this article at: http://www.jci.org/articles/view/73202?key=49651bddb9504dbf286f
Identification of a genetic mutation associated with steroid-resistant nephritic syndrome
Patients with nephritic syndrome exhibit an array of symptoms that are associated with loss of kidney function, including excess protein in urine, swelling, and albuminuria. Many nephritic syndrome patients respond well to treatment with steroids; however, subsets of patients are resistant to steroid treatment and are at high risk of kidney failure. Recent studies have identified single gene mutations that are associated with development of steroid-resistant nephritic syndrome; however, these mutations account for approximately half of all steroid-resistant cases. In this issue of the Journal of Clinical Investigation, Friedhelm Hildebrandt and colleagues at Boston Children's Hospital identified mutations in gene encoding the aarF domain containing kinase 4 (ADCK4) in 15 individuals with steroid-resistant nephritic syndrome from 8 different families. The authors found that cells isolated from patients with ADCK4 mutations had reduced levels of coenzyme Q10 (CoQ10), and decreased mitochondrial respiration. Furthermore, one patient with ACDK4-assocatiated steroid-resistant nephritic syndrome showed improvement following treatment with CoQ10. In their companion commentary, Laura Malaga-Dieguez and Katalin Susztak of the University of Pennsylvania suggest that CoQ10 treatment may be promising for a subset of patients with steroid-resistant nephritic syndrome.
TITLE: ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption
AUTHOR CONTACT: Friedhelm Hildebrandt
HHMI/Boston Children's Hospital, Boston, MA, USA
Phone: 617-355-6129; Fax: 617-730-0365; E-mail: friedhelm.hildebrandt@childrens.harvard.edu
View this article at: http://www.jci.org/articles/view/69000?key=9aeeb2804ee3135671b5
ACCOMPANYING COMMENTARY
TITLE: ADCK4 "reenergizes" nephrotic syndrome
AUTHOR CONTACT: Katalin Susztak
University of Pennsylvania, Philadelphia, PA, USA
Phone: 215-662-7934; Fax: ; E-mail: ksusztak@mail.med.upenn.edu
View this article at: http://www.jci.org/articles/view/73168?key=b544e88ac6b999168409
Insights into type 2B von Willebrand disease
In response to blood vessel damage, von Willebrand factor (vWF) binds to the exposed extra cellular matrix, recruits platelets to the site of injury, and activates platelets, which promotes thrombis formation. Patients with von Willebrand disease type 2B (vWD-type 2B) produce a vWF protein that has a high binding affinity for platelets; however, these patients exhibit a bleeding tendency that is thought to be due to loss of vWF multimers. In this issue of the Journal of Clinical Investigation, Marijke Bryckaert and colleagues at the Hôpital Kremlin Bicêtre determined that the bleeding phenotype associated with vWD-type 2B might be due to platelet dysfunction. Evaluation of platelets treated with vWD-type 2B-associated vWF revealed the mutatnt vWF was able to bind platelets, but was unable to activate them, thereby inhibiting thrombus formation. In an accompanying commentary, Jerry Ware of the University of Arkansas discusses the implications of this study for treatment of vWD-type 2B
TITLE: von Willebrand factor mutation promotes thrombocytopathy by inhibiting integrin αIIbβ3
AUTHOR CONTACT: Marijke Bryckaert
Inserm U770, Hôpital Kremlin Bicêtre, Le Kremlin Bicêtre, UNK, FRA
Phone: 33 149595642; Fax: 33 146719472; E-mail: marijke.bryckaert@inserm.fr
View this article at: http://www.jci.org/articles/view/69458?key=3f538e18596a90b7d9e6
ACCOMPANYING COMMENTARY
TITLE: Thrombocytopathy and type 2B von Willebrand disease
AUTHOR CONTACT: Jerry Ware
University of Arkansas for Medical Sciences, Little Rock, , USA
Phone: 501-526-6096; Fax: ; E-mail: jware@uams.edu
View this article at: http://www.jci.org/articles/view/73169?key=55eaefd5aca6c9c0b9af
ALSO IN THIS ISSUE
TITLE: AKT activation promotes PTEN hamartoma tumor syndrome–associated cataract development
AUTHOR CONTACT: Thomas White
Stony Brook University School of Medicine, Stony Brook, NY, USA
Phone: 631 444 9683; E-mail: View this article at: http://www.jci.org/articles/view/70437?key=cbc9d2992ff30cf0d8f5
TITLE: Mice generated by in vitro fertilization exhibit vascular dysfunction and shortened life span
AUTHOR CONTACT: Emrush Rexhaj
University Hospital Bern, Inselspital, Bern, , CHE
Phone: +41316321941; Fax: ; E-mail: emrush.rexhaj@insel.ch
View this article at: http://www.jci.org/articles/view/68943?key=d8399609fd839a0e9922
Provided by Journal of Clinical Investigation
