A novel oncogenic network specific to liver cancer initiation

Monday, October 8, 2012

Researchers headed by Erwin Wagner, the Director of the BBVA Foundation-CNIO Cancer Cell Biology Programme at the Spanish National Cancer Research Centre (CNIO), have deciphered how a stress-inducible gene regulator, AP-1, controls the survival of liver tumor-initiating cells. These results, published in the online edition of Nature Cell Biology, could provide new preventive strategies and identify potentially targetable molecules to prevent liver cancer.

Hepatocellular carcinoma (HCC) causes more than 500,000 deaths per year worldwide. While patients with chronic hepatitis virus B and C infections or liver cirrhosis are high-risk populations for HCC, measures aiming at preventing HCC development in these patients are limited. In addition, the long-term prognosis after surgical resection of HCC remains poor, due to the high rate of de novo recurrence and the lack of effective preventive therapy.

The critical step for developing effective preventive therapies, but also diagnostic markers and preventive strategies is to identify targetable molecules and pathways responsible for cancer initiation.

Using genetic mouse models specific for liver cancer initiation, researchers have discovered how the stress-inducible AP-1 gene regulator modulates liver tumor cell death in early stages of liver cancer. Mechanistically, AP-1 controls the expression of the epigenetic modulator SIRT6. Subsequently, SIRT6 represses Survivin, which is involved in programmed cell death.

Importantly, altering these proteins in mice even transiently during the initiation stage markedly impaired liver cancer development in mice.

The relevance of these findings was tested in more than 150 human tissue samples collected in patients from Asia and Europe. A clear correlation between these proteins and liver cancer initiation, but not in advanced HCCs, was observed.

These results connect liver cancer initiation with epigenetics and cell death, and give new insights into why patients with metabolic diseases where SIRT6 is important, are at risk of developing of liver cancer.

"Our study provides not only novel implications for the development of preventive therapies for high risk cirrhotic or post-resection patients, but also a new paradigm how one can molecularly dissect cancer initiation using mouse models in combination with the appropriate human samples", states Latifa Bakiri, author of the study.

The study was initiated in Erwin Wagner?s group at the IMP in Vienna and subsequently carried out at the Spanish National Cancer Research Centre (CNIO) and at the State Key Laboratory of Cell Biology, in Shanghai China led by Lijian Hui.

The study also involves the participation of clinical researchers at Fudan University in Shanghai and the Medical University of Graz, Austria.

###

Centro Nacional de Investigaciones Oncologicas (CNIO): http://www.cnio.es

Thanks to Centro Nacional de Investigaciones Oncologicas (CNIO) for this article.

This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.

This press release has been viewed 28 time(s).

Source: http://www.labspaces.net/124259/A_novel_oncogenic_network_specific_to_liver_cancer_initiation

lovelace antioch the grey review demi moore 911 call ipo jim rome ufc on fox 2 weigh ins

Venezuela's Chavez revels in convincing election win

CARACAS (Reuters) - Venezuelan President Hugo Chavez pledged to deepen his socialist revolution after a comfortable election victory that could extend his divisive leadership of the OPEC nation to two decades.

The new six-year term clears the way for Chavez to consolidate state control over Venezuela's economy, possibly with more nationalizations, and continue his support for left-wing allies in Latin America and around the world.

The victory also cements his status as a dominant figure in modern Latin American history and an icon of the political left. But the slimmer margin of victory - 10 percentage points, down from 25 points in 2006 - reflected growing frustration among Venezuelans at day-to-day problems such as crime and blackouts, which Chavez will be under pressure to tackle.

Tens of thousands of ecstatic supporters celebrated in the streets around the presidential palace in downtown Caracas overnight, pumping fists in the air after the former soldier was re-elected with 1.5 million more votes than younger rival Henrique Capriles.

"This has been the perfect battle, a democratic battle," the 58-year-old Chavez thundered from the palace balcony around midnight, holding up a replica of the sword of independence hero Simon Bolivar.

"Venezuela will continue along the path of democratic and Bolivarian socialism of the 21st century."

It was an extraordinary victory for a leader who just a few months ago feared for his life as he struggled to recover from cancer. Turnout was a record 80 percent of registered voters, boosting Chavez's democratic credentials despite critics' depiction of him as an autocrat who tramples on private enterprise and silences political foes.

Supporters dripping with sweat strained to catch a glimpse of Chavez from the street below the palace while dancing and drinking rum. "Chavez, the people are with you!" they chanted.

"He will keep protecting the poor, the defenseless and the elderly," said teacher Gladys Montijo, 54, weeping with joy.

In a nod to the opposition's strong showing, Chavez struck a conciliatory note and promised to be more focused in his new term beginning on January 10.

"Today we start a new cycle of government, in which we must respond with greater efficacy and efficiency to the needs of our people," he said. "I promise you I'll be a better president."

Despite Chavez's anti-capitalist rhetoric, Venezuelan bonds are among the most-traded emerging market debt on Wall Street because they offer high yields. But Chavez's victory pushed prices lower on Monday as investors unwound bets that Capriles would pull off an upset.

ALL EYES ON CHAVEZ

A retired lieutenant colonel who first won fame with a failed 1992 coup, Chavez has become Latin America's main anti-U.S. agitator, criticizing Washington while getting close to its adversaries, including Syria and Iran.

A decade-long oil boom has given him tens of billions of dollars for social spending that ranges from free health clinics to new apartment complexes, helping him build a strong following among the poor that no other politician in Venezuela can match.

It has also allowed him to dispense aid to ideological allies from Bolivia to Cuba, where Chavez's victory was met with relief. Cuban leader Raul Castro was among the first foreign leaders to congratulate Chavez, calling the vote a resounding endorsement of the Venezuelan leader's "Bolivarian Revolution."

Chavez sends discounted oil to more than a dozen Central and South American countries. Communist-led Cuba, for example, receives more than 100,000 barrels a day of Venezuelan crude.

Venezuela is often repaid for the oil in services - Cuba sends doctors to Venezuelan slums, others sometimes pay in food and livestock - which puts strain on the finances of state oil company PDVSA.

With the election out of the way, all eyes are on what Chavez will do next. After his landslide win in 2006, he ordered takeovers in the telecommunications, electricity and oil sectors. Some worry he could now extend nationalizations to other corners of the economy, including the banking, food and health industries.

Any recurrence of the pelvic cancer that has already forced him to undergo three operations in Havana since June 2011 could derail his plans.

The constitution states that if an incumbent steps down in the first four years of a six-year term, a new vote would be called - meaning that under such a scenario Capriles or another opposition candidate would have another crack at power.

Chavez, who has looked rejuvenated in recent weeks after a sluggish start to the election campaign, was expected to hold a news conference later on Monday.

Opposition leaders were crushed by the loss. It followed nearly a month of euphoria among Capriles supporters as the 40-year-old polished his stump speeches, held increasingly fervent rallies and appeared to be gaining ground in the polls.

The youthful state governor put on a brave face in his concession speech, hailing his "house-by-house" campaign as the start of a long road to changing the direction of the country.

On Monday, Capriles bared his soul in a flurry of emotional Twitter messages, and urged his followers not to give up.

"I know a lot of people are sad, but we need to bounce back and keep believing that we can and will build a better country," he said.

STATE ELECTIONS LOOM

Capriles and other leaders of the Democratic Unity coalition must now prepare for state governor elections in December, when they will hope at least to increase the opposition's influence. They were hugely disappointed at winning a majority vote in only three of Venezuela's 24 states on Sunday.

The U.S. State Department congratulated the Venezuelan people for the high turnout and generally peaceful voting.

"We believe that the views of the more than 6 million people who voted for the opposition should be taken into account going forward," said State Department spokesman William Ostick.

Though Capriles was indisputably the strongest candidate to face Chavez since the leftist leader was first elected in 1998, few in the opposition thought the fight was fair.

Chavez made ample use of state television and spent 47 hours in "chain" broadcasts that forced other local television stations to carry speeches peppered with political commentary.

He also handed out houses and pensions financed with state funds, often in ceremonies that glorified his administration, while warning that the opposition would cancel such programs.

The spending spree has weakened Venezuela's finances and may force a currency devaluation in early 2013, which would likely spur inflation that has been a top complaint among voters.

Relations with Washington are also likely to remain on edge, though Venezuelan oil has continued to flow to the United States over the years despite diplomatic tensions.

(Additional reporting by Caracas bureau, Daniel Bases in New York and Andrew Quinn in Washington; Writing by Daniel Wallis and Todd Benson; Editing by Andrew Cawthorne, Kieran Murray and Claudia Parsons)

Source: http://news.yahoo.com/venezuela-presidential-vote-looks-set-close-finish-002711524.html

kim kardashian flour bomb hunger games box office xavier joan crawford joan crawford john goodman kendall marshall

T-Mobile announces Galaxy S3 is its best selling device of all time

Android Central

This may come as no surprise to many of us, but T-Mobile mentioned on Twitter a couple days ago that the Samsung Galaxy S III (S3) is the carrier's all-time best-selling device. There's no doubt that the Galaxy S3 (and Galaxy S2 before it) have been monumental hits for Samsung, but T-Mobile also puts a lot of their marketing weight behind these flagships. Considering that it doesn't offer that fruit phone and often misses out on other devices because of exclusivity deals with other carriers, the success of the Galaxy S3 for T-Mobile may be more important as a single device than it is to any other carrier in the US.

Source: T-Mobile (Twitter)

Source: http://feedproxy.google.com/~r/androidcentral/~3/70V756PhYeU/story01.htm

war horse k cups best buy we bought a zoo we bought a zoo ipad accessories port charlotte florida

JCI early table of contents for October 8, 2012

[ Back to EurekAlert! ] Public release date: 8-Oct-2012
[ | E-mail | Share Share ]

Contact: Jillian Hurst
press_releases@the-jci.org
Journal of Clinical Investigation

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, Kln, 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

###


[ Back to EurekAlert! ] [ | E-mail | Share Share ]

?


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.


[ Back to EurekAlert! ] Public release date: 8-Oct-2012
[ | E-mail | Share Share ]

Contact: Jillian Hurst
press_releases@the-jci.org
Journal of Clinical Investigation

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, Kln, 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

###


[ Back to EurekAlert! ] [ | E-mail | Share Share ]

?


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.


Source: http://www.eurekalert.org/pub_releases/2012-10/joci-jet100312.php

top model all stars americas next top model mark buehrle mark buehrle rick perry ad rick perry ad dragnet

Athletes With Eating Disorders | Leisure Fitness Equipment

Article by active.com, Recommended by Sara Mitchell, Leisure Fitness ? Wellness Outreach Team

?I am worried about my daughter. She exercises too much and eats too little. She says she?s fine, but I think she?s becoming anorexic.??

?My Dad yells at me when I binge/purge:?You?re wasting my money!!!??I am working hard to recover from my eating disorder, but he just doesn?t get it. I don?t even try to talk to him anymore.?

Eating disorders can be devastating to not only teams but also to families. Coaches and parents alike want their athletes to eat well and be healthy. The struggling athletes just want people to stop policing their eating and exercise. The athletes have difficulty talking about why they struggle with food; they instead communicate unhappiness by starving or stuffing their bodies. This distracts them from the pain of feeling ?not good enough? and other hard feelings.

Unfortunately, too many athletes struggle with food issues. A survey of more than 400 female collegiate athletes indicated they typically believed their bodies were not good enough and wanted to lose five pounds.

  • 43 percent reported feeling terrified of becoming overweight
  • 22 percent were extremely preoccupied with food and weight
  • 31 percent had irregular or absent menstrual periods (a sign of inadequate fueling)
  • 34 percent had had a stress fracture or broken bone. (Weakened bones and stress fractures are common in athletes who experience loss of regular menstrual periods).
  • 18 percent of the women had/were at risk for having anorexia
  • 34 percent had/were at risk for having bulimia. (Beals,?Int?l J Sports Nutr?2002)

While there are no easy answers to resolving disordered eating, Dr. David Herzog, a psychiatrist at Harvard Medical School who specializes in the treatment of eating disorders, has addressed common issues in his book?Unlocking the Mysteries of Eating Disorders: A Life-Saving Guide to Your Child?s Treatment and Recovery.

Here are some key points that might be helpful if you are the parent, coach or friend of an athlete with food issues. The goal is to help you understand what?s really going on. If you yourself are the struggling athlete, you might want to highlight pertinent information in this article (or Dr. Herzog?s book), and then ask those who care about you to read the passages. This is one way to start a conversation.

? First of all, eating disorders (such as anorexia and bulimia) are a psychological diagnosis, not a nutritional diagnosis. Eating disorders have little to do with food. Food is just the symptom, not the problem.

? Eating disorders affect both girls and boys alike. For boys, society?s rule??men don?t cry??means they are not allowed to express sadness, fears or hurt. If they do, they can easily be ridiculed and rejected. So instead, they may starve or stuff themselves to numb difficult emotions. Some exhaust themselves with excessive exercise. Others take up body building, believing a muscular body means a perfect life. They need to be assured that having feelings in not a sign of weakness.

? Athletes with eating disorders tend to dislike themselves and their bodies. They feel inadequate, not ?good enough.? Dieting seems a good way to fix what is wrong with them and allows them to be good at something?losing weight!

? If the athlete had at one time been pudgy and nagged by parents to slim down, he can now feel praiseworthy and acceptable. Remind him of the many good inner qualities he has that makes him special?kindness, caring, humor, leadership. The athlete needs to learn he is valued as a person, not for what he looks like.

? Athletes with eating disorders tend to be very talented, hardworking people who ache inside and fail to see their strengths. Something inside them says they should always be working or studying or exercising. Taking time to hang out and chat with others makes them feel guilty. They need to learn being ?human??like the rest of is?is a more attainable goal than being ?perfect.?

? Athletes with eating disorders commonly fear they won?t be able to stop eating if they start, so they try to avoid eating. Some consistently restrict their intake; others yoyo between starving and stuffing. In either case, they endure not just physical hunger but also the mental anguish of feeling alone. It?s hard to have much of a social life if you are afraid of (over)eating food.

? If the athlete does not want to eat with the team, nor join family meals, don?t try to force the situation. Rather just acknowledge ?It must be so hard for you when something inside you holds you back.?

? If the athlete starts talking to you about how fat she is, don?t try to correct the misinformation because the athlete will not believe what you say. Rather, try to understand the turmoil. ?It sounds like you are very unhappy with your body?? Allow an opening to share her concerns.

? If an athlete shares the dark secret of having an eating disorder, acknowledge the effort. ?I know this was hard for you to tell me, but I am really glad you did.?

? On the other hand, if you want to confront the athlete who denies, let?s say, struggling with bulimia, do not become a detective to prove him wrong. Rather, try to understand why the athlete hides this and has trouble letting you know. Is he trying to safeguard you from being stressed? Or does he feel ashamed?

? Telling an athlete to ?just eat? does not solve the inner emptiness that is intense, enduring, hard to recognize, and hard to talk about. Plus, the athlete believes eating will make her feel worse. Recommend counseling, not as a means to ?fatten her up,? but to end the loneliness of the disorder and to find inner peace. Just as it?s important to have a good coach to improve athletic performance, it?s also important to have a good ?mental coach? (therapist skilled with eating disorders) to improve quality of life.

Tags: athlete body image, athlete eating disorder, athlete pressure -->

Source: http://blog.leisurefitness.com/2012/10/athletes-with-eating-disorders/

Olympics closing ceremony PGA Championship 2012 John Witherspoon hope solo hope solo george michael meteor shower

So Cute! Natalie Portman Steps Out with Her Son

San Diego Part 2 TT Summit 2011 | Bodybuilding, Supplements ...


At some point it will be up to you ? and ONLY you ? to make a decision. Whether it is who to vote for, what diet to follow, or career to choose, what expert to listen to, or what to believe. There will never be an area of life where every ?expert? is in consensus?not in health, not in real estate, and not in fixing the economy. And that?s GOOD news. Because it gives you the opportunity to choose what is right for you.

Popular Posts

Eat right ? being pregnant is a blessing

Good and proper nutrition during pregnancy is not only necessary for the mother, but very important for the normal development and growth of the fetus as well. The sensation of nausea and vomiting may make sticking your dietary regime difficult during the months of pregnancy, but you have to maintain a balanced diet and also [...]

Inversion therapy help relieve back pain

Inversion therapy is a type of back pain treatment. It is known to work by reducing the impact of gravity and decreasing the compression of the spine. This enables relaxation of the muscles and ligaments that surround the spine. Inversion therapy is performed on a special table known as an inversion table. The individual is [...]

15 minutes of fitness a day can add 3 years to your life

A recent study done in Taiwan and conducted over a period of 13 years, examined 416,000 participants and found that life expectancy can be raised by three years with just 15 minutes of exercise. So even if you have a busy schedule and can?t find the time to engage in elaborate, intensive workouts, you can [...]

Michael Kuiper

TRAINING: two workouts daily, mixing kickboxing, judo, jiu-jitsu, and wrestling When and why did you start training for fighting? I?ve been doing judo since I was six, and MMA when I was 19 What ranks and titles have you held? 2x Judo champion Do you have any heroes? Amir Sadollah. That guy is awesome and [...]

Lose weight fast with hypothyroidism

Hypothyroidism is one of the most common disorders of the thyroid gland. It is the condition when the thyroid gland does not produce enough thyroid glands and causes our body to suffer in many ways. This condition can cause health problems, such as weight gain, dry skin, besides fatigue and in some cases, intolerance to [...]

Source: http://stek.org/health-fitness/san-diego-part-2-tt-summit-2011/

geraldo obama trayvon martin pietrus cheney tori spelling marion barber marion barber

Elder care laws needed to protect employees | San Francisco ...

Many adult children routinely care for or help care for ill and aging parents. With the number of individuals age 65 and older expected to nearly double by 2030 to an estimated 70 million, more and more adult children will take over the responsibility of caring for an aging parent. This has many concerned about possible workplace and elder care discrimination.

Discrimination by employers against adult caregivers is a growing concern for many employees and elder advocates. In one instance, an employee was fired for taking a leave of absence to care for a dying parent. Another woman was chastised by her employer and denied leave when she requested time off to care for her sick mother.

While some laws and protections currently exist for workers who must care for an elderly parent, many employees do not meet requirements to qualify. An employee is only eligible to file a claim under the Family Medical Leave Act if they and their employer meet certain requirements.

To qualify for FMLA, the employee must have worked at the company for at least one year and the employer must have at least 50 employees. These requirements automatically disqualify many elder care providers who work at small businesses.

The growing number of individuals age 65 and older coupled with an increase in the number of women that work outside the home, has made elder care a major issue for many employers. The number of discrimination cases related to elder care has grown considerably in recent years. In one case, a jury awarded a health care worker $11.65 million dollars after he was fired for taking time to care for his parents who were both suffering debilitating diseases.

Growing concern over matters related to elder care and employees' need to take leaves of absence have lead the state of California to explore legislation protecting workers' rights. As more and more Americans pass into their golden years, other states will also be forced to examine laws governing employee rights with regard to elder care.

Source: Forbes, "Sex Discrimination, Age Discrimination, Family Responsibilities Discrimination?," Ashlea Ebeling, Sept. 10, 2012

Source: http://www.sanfrancisco-employment-lawyer.com/2012/09/elder-care-laws-needed-to-protect-employees.shtml

elvis presley elvis presley vanessa bryant vanessa bryant Prince Harry naked Prince Harry Vegas powerball

West accuses Iran of shipping arms to Syria

(AP) ? The four Western powers trying to rein in Iran's nuclear program accused Tehran on Thursday of shipping arms to Syria in violation of U.N. sanctions and ignoring demands to open key nuclear facilities to U.N. inspectors.

The United States, Britain, France and Germany expressed growing concern that Iran's goal is building a nuclear arsenal ? not nuclear power plants for peaceful civilian use, as Tehran insists.

U.S. Ambassador Susan Rice told a Security Council meeting on the implementation of U.N. sanctions that members can't be complacent about Iran's "latest leaps forward in its prohibited nuclear activities."

"We must recognize that we are facing a situation that continues to worsen," she said.

A spokesman for Iran's mission to the U.N. did not immediately respond to an email seeking comment.

Rice and ambassadors from the other Western powers expressed serious concern at Iran's arms exports to President Bashar Assad's regime in violation of a U.N. ban against all weapons exports.

She reiterated the conclusion of the panel of experts monitoring implementation of sanctions that Syria is now the "central party to illicit Iranian arms transfers."

Britain's U.N. Ambassador Mark Lyall Grant said Iran's supply of weaponry to Syria is unacceptable and it must stop.

"It is in stark contrast to the will of the Syrian people and a reminder of Iran's hypocrisy in claiming to support freedom in the Arab world," he said.

France's U.N. Ambassador Gerard Araud accused Assad of massacring his own people and urged rigorous implementation of sanctions to keep Iran from providing his forces with the arms to accomplish his "sinister work."

Rice called on states in the region to "work together and redouble their efforts to deny, inspect and seize illicit Iranian shipments."

The 18-month Syrian conflict has escalated to a civil war which has killed more than 23,000 people, according to activists.

Germany's U.N. Ambassador Peter Wittig said reports indicate Iran is shipping arms to Syria "under a humanitarian pretext," which makes it crucial that all countries enforce the sanctions to keep pressure on Iran.

Russia and China, who have vetoed three Western-backed resolutions aimed at pressuring the Assad regime to end the violence and start talks with the opposition, made no mention of Iranian arms shipments to Syria in their speeches to the council but did address the nuclear issue.

On Iran's nuclear program, the Western powers expressed alarm at the latest report from the International Atomic Energy Agency. It said Iran has effectively shut down a probe of a site suspected of being used for work on nuclear weapons development while doubling the number of machines it could use to make the core of nuclear warheads at an underground bunker safe from airborne attack.

The nuclear concerns will be at the top of the agenda at a ministerial meeting of the four Western powers, Russia and China on Sept. 27 on the sidelines of the annual General Assembly gathering of world leaders that begins Tuesday.

"The Iranian regime is at a crossroads," Britain's Lyall Grant told the council. "It can continue to ignore the international community's concerns over its nuclear program, or it can negotiate a settlement that will help to realize the benefits of a civil nuclear program. It can support the oppressive regime in Syria in suppressing freedom, or it can play a constructive role in the region. It can be an exporter of terrorism or a responsible member of the international community."

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/cae69a7523db45408eeb2b3a98c0c9c5/Article_2012-09-20-UN-UN-Iran-Sanctions/id-38396ffc50604777bdc5b2899019a687

howard hughes nationwide race wanderlust gone tyler perry good deeds pretty in pink nba all star game

Video: Romney's surprising money problem

Fiona Apple concert postponed after hash arrest

Singer Fiona Apple, who was arrested Wednesday in Texas for possession of hashish and marijuana, was released from jail Thursday after posting a $10,000 bond, the Hudspeth County Sheriff's Office said. Her Austin concert planned for Thursday night will be rescheduled.

Source: http://www.msnbc.msn.com/id/3036697/vp/49110773#49110773

weta rudolph the red nosed reindeer rudolph the red nosed reindeer adam carolla rick neuheisel Cruel Summer