(Press-News.org) Sinusitis: Leaving a bad taste in your mouth
The immune system protects the upper respiratory tract from bacterial infections, but the cues that alert the immune system to the presence of bacteria are not known. In this issue of the Journal of Clinical Investigation, researchers led by Noam Cohen at the University of Pennsylvania demonstrated that the bitter taste receptor T2R38 regulates the immune defense of the human upper airway. Cohen and colleagues found that T2R38 was expressed in the cells that line the upper respiratory tract and could be activated by molecules secreted by Pseudomonas aeruginosa and other bacteria. Additionally, they found that common polymorphisms in the T2R38 gene were correlated with the incidence of bacterial sinus infections. These results demonstrate that genetic variation contributes to individual differences in susceptibility to respiratory infection. In a companion piece, Alice Prince of Columbia University discusses the role of bitter taste receptors in immune defense.
TITLE:
T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection
AUTHOR CONTACT:
Noam Cohen
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
Phone: 215-823-5800 ext 3892; Fax: 215-349-5977; E-mail: cohenn@uphs.upenn.edu
View this article at: http://www.jci.org/articles/view/64240?key=8713f7c1bd015e43f32d
ACCOMPANYING COMMENTARY
TITLE:
The bitter tast of infection
AUTHOR CONTACT:
Alice S. Prince
Columbia University, New York, NY, USA
Phone: 212/305-4193; Fax: 212-305-2284; E-mail: asp7@columbia.edu
View this article at: http://www.jci.org/articles/view/66182?key=3da926f3262c7c8e0664
Synaptic protein linked to Levodopa-induced dyskinesia
Dopamine replacement is a standard treatment for Parkinson's disease; however, one of the side effects is a movement disorder known as Levodopa-induced dyskinesia (LID). In a study published in the Journal of Clinical Investigation, Erwan Bezard and colleagues at the University of Bordeaux found that the protein PSD-95, which which organizes proteins at neuronal synapses, was overexpressed in monkeys with LID. PSD-95 determines the cellular localization of the D1 dopamine receptor (D1R) and excess PSD-95 altered dopamine signaling to induce LID symptoms . By disrupting the interaction between D1R and PSD-95, Bezard and colleauges were able to improve LID symptoms in rats and monkeys. Imaging studies revealed that loss of PSD-95 reduced the amount of D1R at the synapse. These studies suggest that PSD-95 may be a suitable therapeutic target to ameliorate a major side effect of Parkinson's disease treatment.
TITLE:
PSD-95 expression controls L-dopa dyskinesia through Dopamine D1 receptor trafficking
AUTHOR CONTACT:
Erwan Bezard
CNRS UMR 5543, Bordeaux, , FRA
Phone: +33557574762; Fax: +33556901421; E-mail: erwan.bezard@umr5543.u-bordeaux2.fr
View this article at: http://www.jci.org/articles/view/59426?key=12bc325376cad5452bf0
Researchers elucidate role of progranulin in frontotemporal dementia
Loss of one copy of the gene that codes for the protein progranulin (PGRN) is a major cause of frontotemporal dementia; however, the mechanism by which loss of PGRN causes neurodegeneration is unknown. In a study published in the Journal of Clinical Investigation, researchers led by Robert Farese at the University of California, San Francisco, demonstrated that loss of PGRN increased neuron loss in response to CNS injury in mice. PGRN was required to attenuate the post-injury inflammatory response that causes neuronal damage. These findings suggest that PGRN deficiency may contribute to increased neural inflammation and subsequent neurodegeneration.
TITLE:
Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury
AUTHOR CONTACT:
Robert Farese, Jr.
University of California, San Francisco, San Francisco, CA, USA
Phone: 415-734-2000; Fax: 415-355-0960; E-mail: bfarese@gladstone.ucsf.edu
View this article at: http://www.jci.org/articles/view/63113?key=20438e27a6b211302a62
Defining the pathogenesis of spinocerebellar ataxia
Spinocerebellar ataxia 28 (SCA28) is an inherited neuropathy characterized by a lack of muscle coordination affecting the limbs and the muscles that control the eyes. Mutations in the AFG3L2 gene have been linked to SCA28, but the pathogenic mechanism is undefined. In a study published in the Journal of Clinical Investigation, researchers led by Elena Rugarli at the University of Cologne found that AFG3L2 was required for the survival of Purkinje cells, which are involved in the coordination of movement. Using AFG3L2-mutant mice, Rugarli and colleagues demonstrated that Purkinje cells expressing mutant AFG3L2 had defects in mitochondrial protein synthesis that eventually killed the cells, leading to neurodegeneration and the movement disorder that characterizes SCA28.
TITLE:
AFG3L2 supports mitochondrial protein synthesis and Purkinje cell survival
AUTHOR CONTACT:
Elena Rugarli
Center for Molecular Medicine, University of Cologne, Köln, UNK, DEU
Phone: +49 221 470 8290 (office); Fax: + 49 221 470 8590; E-mail: elena.rugarli@uni-koeln.de
View this article at: http://www.jci.org/articles/view/64604?key=de37c55e6c7158264e15
Hedgehog signaling is associated with poor clinical outcome in intermediate risk prostate cancer
Prostate cancer patients are classified into low, intermediate, and high-risk groups that reflect relative survival categories. While there are accepted treatment regimens for low and high-risk patients, intermediate risk patients pose a clinical dilemma, as treatment outcomes are highly variable for these individuals. In this issue of the Journal of Clinical Investigation, Ruth Muschel and colleagues at the University of Oxford identified the protein PN1 as a negative regulator of the oncogenic Hedgehog signaling pathway in prostate cancer. In a mouse model of prostate cancer, increased expression of PN1 inhibited tumor growth. Further, comparisons of tumor tissue from human prostate cancer patients showed that genetic alterations in Hedgehog pathway regulators correlated with worse clinical outcomes in intermediate risk patients.
TITLE:
Protease Nexin 1 inhibits hedgehog signaling in prostate adenocarcinoma
AUTHOR CONTACT:
Ruth Muschel
University of Oxford, Oxford, UNK, GBR
Phone: +44 1865 225847; Fax: +44 1865 857533; E-mail: ruth.muschel@gmail.com
View this article at: http://www.jci.org/articles/view/59348?key=f202b12d4c35856085af
MicroRNA-155 influences atherosclerotic plaque formation
Atherosclerosis causes the thickening and hardening of the arteries. Macrophages participate in the formation of atherosclerotic plaques by driving inflammatory responses, accumulating LDL, and releasing factors that influence the behavior of cells within the plaque. MicroRNAs (miRs) control the activity of macrophages by regulating gene expression, but the exact roles of different miRs remain undefined. In a study published in the Journal of Clinical Investigation, Andreas Schober and colleagues at Ludwig Maximilians University in Munich, Germany report that miR-155 is induced by LDL and inflammatory factors in macrophages. Expression of miR-155 in macrophages reduced atherosclerotic plaque formation in mice by repressing the transcription factor Bcl6, which attenuates inflammatory signaling pathways. This study demonstrates that miR-155 plays a key role in macrophage-mediated vascular inflammation in atherosclerosis.
TITLE:
MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages
AUTHOR CONTACT:
Andreas Schober
LMU Munich, Munich, , DEU
Phone: 49-89-51605151; E-mail: aschober@med.lmu.de
View this article at: http://www.jci.org/articles/view/61716?key=d4983c810db5e81a2a97
A new model of Shiga toxin-producing E. coli infection
Shiga toxin-producing E. coli (STEC) have been implicated in multiple outbreaks of food-borne illness and can cause intestinal and systemic disease, including severe renal damage. Upon attachment to the intestine, STEC generate lesions that allow the shiga toxin to cross the intestinal wall and enter the blood stream. Current mouse models of STEC do not accurately reflect this aspect of the human disease and the molecular mechanisms that allow the Shiga toxin to enter the blood stream are undefined. In a study published in the Journal of Clinical Investigation, John Leong and colleagues at Tufts University developed a mouse model of STEC infection that replicated the intestinal damage seen in the human disease. This new model will serve as a platform to determine how STEC crosses the intestinal wall to cause systemic disease.
TITLE:
A novel murine infection model for Shiga toxin-producing Escherichia coli
AUTHOR CONTACT:
John Leong
Tufts University School of Medicine, Boston, MA, USA
Phone: 617-636-0488; Fax: 617-636-0335; E-mail: John.Leong@tufts.edu
View this article at: http://www.jci.org/articles/view/62746?key=748f1dbd5c1c949d3eb4
Viral antigen cross-presentation protects dendritic cells from infection
Dendritic cells (DC) are gatekeepers that patrol the body, looking for signs of infection. Once they find a virus, they sample a bit of the virus and present the viral antigens to T cells, which are responsible for finding and killing infected cells. The role of DC antigen cross-presentation in the induction of anti-viral cytotoxic T cells is not entirely clear. In a study published in the Journal of Clinical Investigation, researchers led by Miriam Merad at Mount Sinai Medical School used a recombinant, fluorescent influenza virus to visualize antigen presentation of DC cells in the lungs of mice infected with influenza. They found that a specific subset of DC cells (CD103+) carried fluorescent virus to the lymph nodes, where they induced virus-specific T cells. Additionally, cross-presenting DCs were protected from viral infection.
TITLE:
Cross-presenting CD103+ dendritic cells are protected from influenza virus infection
AUTHOR CONTACT:
Miriam Merad
Mount Sinai School of Medicine, New York, NY, USA
Phone: (212) 659-8276; Fax: ; E-mail: miriam.merad@mssm.edu
View this article at: http://www.jci.org/articles/view/60659?key=75c26e6afdda1d2ec0bb
Endotrophin links obesity to breast cancer progression
Fat cells (adipocytes) surround breast tumors and contribute to tumor growth by expressing factors that aid oncogenesis. Col6 is a protein that is highly expressed in adipocytes and its expression is further increased in both obesity and in breast cancer cells. In this issue of the Journal of Clinical Investigation, Phillip Scherer and Jiyoung Park of the University of Texas Southwestern Medical Center report that a portion of the Col6 protein, known as endotrophin, alters the tumor environment to promote tumor growth and metastasis in mice. Mice with reduced endotrophin expression had significantly less tumor burden and fewer metastases. These findings link obesity and cancer progression and suggest that endotrophin may serve as novel therapeutic target in the treatment of breast cancer.
TITLE:
Endotrophin links obesity to breast cancer progression
AUTHOR CONTACT:
Philipp E. Scherer
The University of Texas Southwestern Medical Center, Dallas, TX, USA
Phone: (214) 648-8715; Fax: (214) 648-8720; E-mail: philipp.scherer@utsouthwestern.edu
View this article at: http://www.jci.org/articles/view/63930?key=9c997068a1667266d6f6
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JCI early table of contents for October 8, 2012
2012-10-08
ELSE PRESS RELEASES FROM THIS DATE:
Sinusitis: Leaving a bad taste in your mouth
2012-10-08
The immune system protects the upper respiratory tract from bacterial infections, but the cues that alert the immune system to the presence of bacteria are not known. In this issue of the Journal of Clinical Investigation, researchers led by Noam Cohen at the University of Pennsylvania demonstrated that the bitter taste receptor T2R38 regulates the immune defense of the human upper airway. Cohen and colleagues found that T2R38 was expressed in the cells that line the upper respiratory tract and could be activated by molecules secreted by Pseudomonas aeruginosa and other ...
Endotrophin links obesity to breast cancer progression
2012-10-08
Fat cells (adipocytes) surround breast tumors and contribute to tumor growth by expressing factors that aid oncogenesis. Col6 is a protein that is highly expressed in adipocytes and its expression is further increased in both obesity and in breast cancer cells. In this issue of the Journal of Clinical Investigation, Phillip Scherer and Jiyoung Park of the University of Texas Southwestern Medical Center report that a portion of the Col6 protein, known as endotrophin, alters the tumor environment to promote tumor growth and metastasis in mice. Mice with reduced endotrophin ...
Use of fresh red blood cells for transfusions for premature infants does not improve outcomes
2012-10-08
CHICAGO – Among premature, very low-birth-weight infants requiring a transfusion, use of fresh red blood cells (RBCs) compared with standard RBC transfusion practice did not improve clinical outcomes that included rates of complications or death, according to a study in the October 10 issue of JAMA. The study is being published early online to coincide with its presentation at the AABB (formerly the American Association of Blood Banks) Annual Meeting.
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Fresh blood not better, clinical trial shows
2012-10-08
October 8, 2012, Ottawa — In a finding that runs counter to commonly held beliefs about fresh being better, a clinical trial published today by the Journal of the American Medical Association shows that acutely ill premature babies who received fresher blood did not fare better than those who received the current standard of care. There was no difference between the two approaches with respect to major organ injury, mortality and infection.
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Gladstone scientists identify biological mechanism that plays key role in early-onset dementia
2012-10-08
SAN FRANCISCO, CA—October 8, 2012—Using animal models, scientists at the Gladstone Institutes have discovered how a protein deficiency may be linked to frontotemporal dementia (FTD)—a form of early-onset dementia that is similar to Alzheimer's disease. These results lay the foundation for therapies that one day may benefit those who suffer from this and related diseases that wreak havoc on the brain.
As its name implies, FTD is a fatal disease that destroys cells, or neurons, that comprise the frontal and temporal lobes of the brain—as opposed to Alzheimer's which mainly ...
New study reveals bitter taste receptors regulate the upper respiratory defense system
2012-10-08
PHILADELPHIA – A new study from a team of researchers at the Perelman School of Medicine at the University of Pennsylvania, the Monell Chemical Senses Center, and the Philadelphia VA Medical Center, reveals that a person's ability to taste certain bitter flavors is directly related to their ability to fight off upper respiratory tract infections, specifically chronic sinus infections. The new research is published in the latest edition of the Journal of Clinical Investigation.
Most humans experience five types of tastes: sweet, salty, sour, bitter, and savory. The ...
Study finds nearly 50% of retail firewood infested with insects
2012-10-08
A new study published in the Journal of Economic Entomology reports that live insects were found in 47% of firewood bundles purchased from big box stores, gas stations and grocery stores in Colorado, New Mexico, Utah and Wyoming.
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Smallest and fastest-known RNA switches provide new drug targets
2012-10-08
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Breathe in, breathe out: New way of imaging lungs could improve COPD diagnosis and treatment
2012-10-08
ANN ARBOR, Mich. — A new approach to lung scanning could improve the diagnosis and treatment of a lung disease that affects approximately 24 million Americans and is the country's third-highest cause of death.
In a new paper published online in Nature Medicine, a team from the University of Michigan Medical School reports on a technique called parametric response mapping, or PRM. They used PRM to analyze computed tomography, or CT, scans of the lungs of patients with chronic obstructive pulmonary disease, known as COPD, who took part in the national COPDGene study funded ...
UCLA researchers discover that the sleeping brain behaves as if it's remembering something
2012-10-08
UCLA researchers have for the first time measured the activity of a brain region known to be involved in learning, memory and Alzheimer's disease during sleep. They discovered that this part of the brain behaves as if it's remembering something, even under anesthesia, a finding that counters conventional theories about memory consolidation during sleep.
The research team simultaneously measured the activity of single neurons from multiple parts of the brain involved in memory formation. The technique allowed them to determine which brain region was activating other areas ...