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JCI early table of contents for Nov. 19, 2012

2012-11-19
(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 ### END


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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
Many of the world's most unfamiliar species are just sitting around on museum shelves collecting dust. That's according to a report in the November 20th issue of the Cell Press journal Current Biology showing that it takes more than 20 years on average before a species, newly collected, will be described. It's a measure the researchers refer to as the species' "shelf life," and that long shelf life means that any conservation attempts for unknown, threatened species could come much too late. The problem, the researchers say, is due to a lack of experts and of the funding ...

No elevated 10-year risk of heart disease for people who become ill during a large E. coli outbreak

2012-11-19
According to a new study in CMAJ (Canadian Medical Association Journal), people who became ill during the Walkerton, Ontario, Escherichia coli O157:H7outbreak were not at greater risk of heart disease or stroke 10 years later. E. coli O157:H7 is a common cause of 'food poisoning." This bacterium most recently caused the outbreak involving beef from XL foods (Alberta) in September 2012, and was the major cause of illness during the large Walkerton E. coli outbreak in May 2000. In the United States, there are 63 000 infections each year, with 12 major outbreaks since 2006. ...

Toward competitive generic drug prices in Canada

2012-11-19
The commitment of Canadian premiers to lower generic drug prices is a major change in how the country prices generic drugs, and government should learn from past attempts, states an article published in CMAJ (Canadian Medical Association Journal). Generic drug prices are higher in Canada than in other industrialized countries. The authors argue that the premiers' call for a national bulk purchasing program, made earlier in 2012, is a positive step for Canadians. "The joint commitment from Canada's premiers to use coordinated bulk purchasing to lower these prices is ...

Major advance in using sunlight to produce steam without boiling water

2012-11-19
WASHINGTON, Nov. 19, 2012 — Scientists today are describing a revolutionary new way to use sunlight to produce steam and other vapors without heating an entire container of fluid to the boiling point. The advance, reported in the American Chemical Society (ACS) journal ACS Nano, has potential applications, especially in the poverty-stricken areas of the developing world, that include inexpensive, compact devices for purification of drinking water, sterilization of medical instruments and sanitizing sewage. "This research opens up a revolutionary new application of nanoparticles ...

Does your job increase your breast cancer risk?

2012-11-19
Is there a link between the risk of breast cancer and the working environment? A study published in BioMed Central's open access journal Environmental Health provides further evidence on this previously neglected research topic, confirming that certain occupations do pose a higher risk of breast cancer than others, particularly those that expose the worker to potential carcinogens and endocrine disrupters. Breast cancer is the most frequent cancer diagnosis among women in industrialized countries, and North American rates are among the highest in the world. Endocrine-disrupting ...

Many seniors' sleep habits are similar to those of young adults, study suggests

2012-11-19
PITTSBURGH, Nov. 19, 2012 – More than half of all retired people aged 65 and over report sleeping at least 7.5 hours per night, and between the hours of 11 p.m. and 7:30 a.m., contrary to commonly held assumptions that most elderly go to bed early and have trouble sleeping through the night, according to a study by researchers at the University of Pittsburgh's Sleep and Chronobiology Center (SCC) and University Center for Social and Urban Research (UCSUR). This new study, supported by a grant from the National Institute on Aging, was conducted over five years and is among ...

Mosquitos fail at flight in heavy fog

2012-11-19
Mosquitos have the remarkable ability to fly in clear skies as well as in rain, shrugging off impacts from raindrops more than 50 times their body mass. But just like modern aircraft, mosquitos also are grounded when the fog thickens. Researchers from the Georgia Institute of Technology present their findings at the 65th meeting of the American Physical Society's (APS) Division of Fluid Dynamics, Nov. 18 - 20, in San Diego, Calif. "Raindrop and fog impacts affect mosquitoes quite differently," said Georgia Tech researcher Andrew Dickerson. "From a mosquito's perspective, ...

Invisibility cloaking to shield floating objects from waves

2012-11-19
A new approach to invisibility cloaking may one day be used at sea to shield floating objects – such as oil rigs and ships – from rough waves. Unlike most other cloaking techniques that rely on transformation optics, this one is based on the influence of the ocean floor's topography on the various "layers" of ocean water. At the American Physical Society's (APS) Division of Fluid Dynamics (DFD) meeting, being held November 18-20, 2012, in San Diego, Calif., Reza Alam, assistant professor of mechanical engineering at the University of California, Berkeley, will describe ...

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[Press-News.org] JCI early table of contents for Nov. 19, 2012