(Press-News.org) A code of silence in acute myeloid leukemia
The development of acute myeloid leukemia (AML) is associated with a variety of genetic changes. Some of these alterations are epigenetic, wherein the sequence of the genes is unchanged, but chemical modifications to the DNA alters gene expression. In a study published in the Journal of Clinical Investigation, researchers led by Daniel Tenen at Beth Israel Deaconess Medical Center found that a transcriptional regulator known as C/EBPG was highly expressed in a subset of AML samples that had an epigenetically silenced C/EBPA gene. By blocking the epigenetic modification of C/EBPA, Tenen and colleagues found that they could reduce C/EBPG and restore normal myeloid blood cells. This study suggests that targeting the balance of C/EBPG and C/EBPA could represent a new therapeutic approach in the treatment of AML.
TITLE:
C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia
AUTHOR CONTACT:
Daniel Tenen
Beth Israel Deaconess Medical Center, Boston, MA, USA
Phone: 617-735-2235; Fax: 617-735-2222; E-mail: dtenen@bidmc.harvard.edu
View this article at: http://www.jci.org/articles/view/65102?key=2caafbb63e0b6ae08fa7
Immune cells fail to migrate in Huntington's disease
Huntington disease (HD) is an incurable neurodegenerative disease caused by a mutation in the huntingtin gene (htt). Though most of the symptoms of HD are neurological, the mutant HTT protein is expressed in non-neural cells as well. In this issue of the Journal of Clinical Investigation, researchers led by Paul Muchowski at the J. David Gladstone Institutes in San Franscisco examined the role of immune cells in HD. Immune cells known as microglia, which were isolated from the brains of HD mice, as well as immune cells from the peripheral blood were found to be defective in their ability to migrate. Interestingly, the immune cell defects were apparent prior to the onset of HD symptoms. This study suggests that changes in immune cell function may underlie some of the symptoms of HD.
TITLE:
Mutant huntingtin impairs immune cell migration in Huntington disease
AUTHOR CONTACT:
Paul Muchowski
J. David Gladstone Institutes, San Francisco, CA, USA
Phone: 415-734-2515; E-mail: pmuchowski@gladstone.ucsf.edu
View this article at: http://www.jci.org/articles/view/64484?key=ed9b525e3a43db3e13d8
T cell development remains intact after loss of thymic function
Bone marrow transplant (BMT) patients and the elderly suffer from a loss of thymic function, resulting in low T cell production and greater susceptibility to infection. Several previous studies have indicated that T cells can develop outside the thymus; however, it is unclear if these cells are fully functional. In this issue of the Journal of Clinical Investigation, researchers led by Marcel van den Brink at Memorial Sloan-Kettering Hospital used a mouse model of BMT to determine if extrathymic T cell development could produce functional T cells. Van den Brink and colleagues found that mice with impaired thymic function after BMT produced fully functional T cells, demonstrating that lymph nodes can support T cell development in the absence of thymic function. These results suggest that patients with limited thymic function can still produce functional T cells and that these pathways could be therapeutically targeted to enhance functional T cell populations.
TITLE:
Extrathymic development of murine T cells after bone marrow transplantation
AUTHOR CONTACT:
Marcel R.M. van den Brink
Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Phone: 646-888-2304; Fax: 917-432-2375; E-mail: vandenbm@mskcc.org
View this article at: http://www.jci.org/articles/view/60630?key=f4013c21c2eed05dbc54
Treating muscle weakness in myotopic dystrophy
Myotopic Dystrophy type 1 (DM1), also known as Steinert disease, is a congenital neuromuscular disease characterized by wasting of the muscle, muscle weakness, endocrine changes, and cognitive problems. It is caused by the insertion of nucleotide repeats in the DMPK gene. In this issue of the Journal of Clinical Investigation, researchers led by Lubov Timchenko at Baylor College of Medicine used a mouse model of DM1 to identify dysregulated signaling pathways that contribute to disease progression. Timchenko and colleagues found that GSK3β signaling was increased in DM1 mice and that inhibition of GSK3β reduced muscle weakness and wasting. These results suggest that therapies that normalize GSK3β activity may help improve muscle function in DM1 patients.
TITLE:
GSK3β mediates muscle pathology in myotonic dystrophy
AUTHOR CONTACT:
Lubov Timchenko
Baylor College of Medicine - BCM 315, Houston, TX, USA
Phone: 713 798 6911; E-mail: lubovt@bcm.tmc.edu
View this article at: http://www.jci.org/articles/view/64081?key=3a6f408e3f25b9e3c14c
HIV-1 infection generates microparticles that kill immune cells
HIV-1 disables the immune system, leaving patients susceptible to viral and bacterial infections. Dendritic cells (DCs) are a population of immune cells that are involved in controlling HIV infection, leading Nina Bhardwaj and researchers at New York University to hypothesize that factors elicited by HIV-1 might block the function of DCs. In this issue of the Journal of Clinical Investigation, Bhardwaj and colleagues report that microparticles found in the plasma of HIV-1 patients inhibited the function of normal DCs and induced dendritic cell death. These results suggest that inhibition of these microparticles could promote DC activity and survival and help fight HIV-1.
TITLE:
HIV-1 infection–induced apoptotic microparticles inhibit human DCs via CD44
AUTHOR CONTACT:
Nina Bhardwaj
NYU School of Medicine, New York, NY, USA
Phone: 1 212 263 5814; Fax: 2122636729; E-mail: nina.bhardwaj@nyumc.org
View this article at: http://www.jci.org/articles/view/64439?key=1d6cff10286e34fcfebf
B cells cross the blood-brain barrier in multiple sclerosis
In multiple sclerosis (MS), the blood-brain barrier (BBB) is compromised, allowing immune cells to attack the central nervous system (CNS). B cells are a population of immune cells that are thought to trigger autoimmune responses in MS, but it is unclear if they are able to transverse the BBB. In this issue of the Journal of Clinical Investigation, researchers led by Hans-Christian von Büdingen at the University of California, San Francisco, studied the ability of B cells to move between the peripheral blood and the CNS. By comparing the antibodies in the cerebrospinal fluid and the blood stream, von Büdingen and colleagues found populations of B cells that are common to both areas in patients with MS. This study demonstrates that B cells can cross the BBB and shows that they are central regulators of the pathological immune response in MS.
TITLE:
B cell exchange across the blood-brain barrier in multiple sclerosis
AUTHOR CONTACT:
Hans-Christian von Büdingen
University of California, San Francisco, San Francisco, CA, USA
Phone: +1- 415-476-9046; Fax: +1-415-476-5229; E-mail: Hans-christian.Vonbuedingen@ucsf.edu
View this article at: http://www.jci.org/articles/view/63842?key=c2030e1d3315891dd835
Viperin protects against Chikungunya virus
Chikungunya virus (CHIKV) is a mosquito-borne virus that causes fever and severe joint pain. It is occurring with increasing frequency in Africa, Asia, and the Indian sub-continent, but there are not any treatments for the disease. The human immune system can eventually repel the virus; however, the immune response mechanisms are undefined. In a study published in the Journal of Clinical Investigation, researchers led by Lisa Ng at the Singapore Immunology Network examined the immune cells of human Chikungunya patients. They found that the expression of the protein viperin increased significantly in monocytes, the cells that are primarily targeted by CHIKV. Viperin attenuated viral replication and mice lacking viperin had a greater viral load and more severe joint inflammation compared to normal mice. These data demonstrate that virperin is a critical host protein that controls CHIKV infections and suggest that therapeutics that modulate viperin may be useful in treating similar viruses.
TITLE:
Viperin restricts chikungunya virus replication and pathology
AUTHOR CONTACT:
Lisa F.P. Ng
Singapore Immunology Network, Singapore, SGP
Phone: +6564070028; E-mail: lisa_ng@immunol.a-star.edu.sg
View this article at: http://www.jci.org/articles/view/63120?key=53eb96677e427a77b8d1
Loss of KLF4 promotes atherosclerosis in mice
Atherothrombosis, or the formation of a clot in an artery, is one of the major causes of heart attack, stroke, and peripheral artery disease. Clot formation is primarily regulated by the endothelium, the cells which line the insides of the arteries and veins. Previously, researchers led by Mukesh Jain at Case Western Reserve University identified KLF4 as a protective factor that was induced by blood flow and was associated with reduced clot formation. In this issue of the Journal of Clinical Investigation, Jain and colleagues examined atherosclerotic plaque formation in KLF4 mutant mice fed a high fat diet. They found that mice lacking KLF4 had significantly enhanced atherosclerosis compared to normal mice, while mice with extra KLF4 had reduced atherosclerosis. These results establish KLF4 as a key regulator of atherothrombosis.
TITLE:
Endothelial Kruppel-like factor 4 protects against atherothrombosis in mice
AUTHOR CONTACT:
Mukesh Jain
Case Western Reserve University, Cleveland, OH, USA
Phone: 216-368-3607; E-mail: mukesh.jain2@case.edu
View this article at: http://www.jci.org/articles/view/66056?key=f81438bdf96cff1c94ff
Mutation in SH2B1 linked to obesity
The protein SH2B1 interacts with cell surface receptors that mediate signaling by insulin and leptin, two hormones that are associated with obesity. Mice lacking Sh2b1 exhibit increased food intake, obesity, and insulin resistance. In a study published in the Journal of Clinical Investigation, researchers led by Sadaf Farooqi at Addenbrooke's Hospital in Cambridge, England identified a mutation in SH2B1 in a group of patients with severe early onset diabetes. These patients had increased food intake, early childhood obesity, insulin resistance, and short stature. This study demonstrates that SH2B1 plays a critical role in human food intake and obesity.
TITLE:
Human SH2B1 mutations are associated with maladaptive behaviors and obesity
AUTHOR CONTACT:
Sadaf Farooqi
Addenbrooke's Hospital, Cambridge, , GBR
Phone: 44-1223-762-634; Fax: 44-1223-762-657; E-mail: isf20@cam.ac.uk
View this article at: http://www.jci.org/articles/view/62696?key=c51ce7657ca422d585fe
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JCI early table of contents for Nov. 19, 2012
2012-11-19
ELSE PRESS RELEASES FROM THIS DATE:
Immune cell migration is impeded in Huntington's disease
2012-11-19
Huntington disease (HD) is an incurable neurodegenerative disease caused by a mutation in the huntingtin gene (htt). Though most of the symptoms of HD are neurological, the mutant HTT protein is expressed in non-neural cells as well. In this issue of the Journal of Clinical Investigation, researchers led by Paul Muchowski at the J. David Gladstone Institutes in San Franscisco examined the role of immune cells in HD. Immune cells known as microglia, which were isolated from the brains of HD mice, as well as immune cells from the peripheral blood were found to be defective ...
A code of silence in acute myeloid leukemia
2012-11-19
The development of acute myeloid leukemia (AML) is associated with a variety of genetic changes. Some of these alterations are epigenetic, wherein the sequence of the genes is unchanged, but chemical modifications to the DNA alter gene expression. In a study published in the Journal of Clinical Investigation, researchers led by Daniel Tenen at Beth Israel Deaconess Medical Center found that a transcriptional regulator known as C/EBPG was highly expressed in a subset of AML samples that had an epigenetically silenced C/EBPA gene. By blocking the epigenetic modification of ...
New species literally spend decades on the shelf
2012-11-19
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2012-11-19
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2012-11-19
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2012-11-19
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Many seniors' sleep habits are similar to those of young adults, study suggests
2012-11-19
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2012-11-19
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Invisibility cloaking to shield floating objects from waves
2012-11-19
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