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"Wind Chill Advisory" ...Wind Chill Advisory now in effect from 1 PM this afternoon to noon EST Sunday... * locations...New York City...Long Island and most of northeastern New Jersey...most of coastal Connecticut... western Bergen and southern Westchester counties. * Hazard types...dangerous wind chills. * Timing...coldest wind chills late tonight into early Sunday morning. * Wind chill...from 18 to 23 degrees below zero due to temperatures around zero...and northwest winds 0 to 30 mph with gusts up to 45 mph. * Cold impacts...the frigid conditions will be dangerous to those venturing outside. Prolonged exposure may cause frostbite. The combination of very low wind chills and frigid air temperatures have the potential to result in frozen pipes...frostbite and hypothermia. * Wind impacts...scattered tree limbs and branches downed. Isolated power outages. Precautionary/preparedness actions... A Wind Chill Advisory means that very cold air and strong winds will combine to generate low wind chills. This will result in frost bite and lead to hypothermia if precautions are not taken. Outdoor exposure should be limited. If you are heading outdoors...dress in layers and keep your hands and head covered to protect against frostbite , "Special Statement" ...Dangerously cold wind chills tonight into Sunday morning... * temperatures tonight into early Sunday morning will fall to zero to 3 degrees below zero in and around the New York City and New Jersey Metro...and Long Island...and coastal Connecticut. Temps will fall to 5 to 10 degrees below across interior portions of northeast New Jersey...the lower Hudson Valley...and southern Connecticut. Wind chill values during this time are expected to reach life threatening levels as cold as 20 to 30 degrees below zero. * High temperatures on Sunday will only be in the teens...with wind chills likely not rising above zero until mid to late afternoon. * Cold spells of this magnitude bring a risk of frostbite and hypothermia for anyone who does not take proper precautions. In addition...frozen pipes and overworked furnaces could leave your house without heat or running water...and car batteries run the risk of dying. * Never venture outdoors without wearing gloves...a hat and several layers of clothing. Wind chill values late Saturday night into Sunday morning could lead to frostbite in less than 30 minutes if proper precautions are not taken. * Run water at a trickle and keep Cabinet doors open to prevent pipes from freezing. * Never use a stove or oven to heat your home or use an open flame to melt frozen pipes. Many house fires result from these practices. * Check tire pressure and your car battery. Be sure your car has a winter safety kit that includes a blanket...warm clothes and gloves in case your car breaks down or becomes stranded. * Take extra steps to keep your pets warm and know their limits to cold. 435 am EST Sat Feb 13 2016 ...Dangerously cold wind chills tonight into Sunday morning... * temperatures tonight into early Sunday morning will fall to zero to 3 degrees below zero in and around the New York City and New Jersey Metro...and Long Island...and coastal Connecticut. Temps will fall to 5 to 10 degrees below across interior portions of northeast New Jersey...the lower Hudson Valley...and southern Connecticut. Wind chill values during this time are expected to reach life threatening levels as cold as 20 to 30 degrees below zero. * High temperatures on Sunday will only be in the teens...with wind chills likely not rising above zero until mid to late afternoon. * Cold spells of this magnitude bring a risk of frostbite and hypothermia for anyone who does not take proper precautions. In addition...frozen pipes and overworked furnaces could leave your house without heat or running water...and car batteries run the risk of dying. * Never venture outdoors without wearing gloves...a hat and several layers of clothing. Wind chill values late Saturday night into Sunday morning could lead to frostbite in less than 30 minutes if proper precautions are not taken. * Run water at a trickle and keep Cabinet doors open to prevent pipes from freezing. * Never use a stove or oven to heat your home or use an open flame to melt frozen pipes. Many house fires result from these practices. * Check tire pressure and your car battery. Be sure your car has a winter safety kit that includes a blanket...warm clothes and gloves in case your car breaks down or becomes stranded. * Take extra steps to keep your pets warm and know their limits to cold. -- Saturday Feb.13 16,07:48 AM Weather  |  LIRR  |  Traffic  |  Traffic Cams |  Weather News

 

New Understanding of a Mechanism by Which Cells Try to Arrest Oncogene Action

Press Releases

CSHL Professor Nicholas Tonks and Benoit Boivin co-led a team that traced the process in exquisite detail.

Cold Spring Harbor, NY - August 28, 2014 - What happens inside cells when they detect the activation of a cancer-inducing gene?  Sometimes, cells are able to signal internally to stop the cell cycle. Such cells are able to enter, at least for a time, a protective non-growth state.  
 
Since the 1980s, scientists have known that mutations in a human gene called RAS are capable of setting cells on a path to cancer.  Today, a team at Cold Spring Harbor Laboratory (CSHL) publishes experiments showing how cells can respond to an activated RAS gene by entering a quiescent state, called senescence.
 
CSHL Professor Nicholas Tonks and Benoit Boivin, now a University of Montreal Assistant Professor, co-led a team that traced the process in exquisite detail. They began by confirming that activation of mutant, oncogenic H-RAS, one of the human RAS oncogene variants, spurs cells to generate hydrogen peroxide (H2O2), a form of reactive oxygen species, or ROS.  “Most people, when they think about ROS, think about the great damage they can do at high concentrations,” says Tonks. “But this research exemplifies how the controlled production of ROS in cells can play a beneficial role.”
 
The team showed how the production of ROS in response to oncogenic H-RAS enables cells to fine-tune signaling pathways, leading them to enter a senescent state. A key part of this process is the impact of ROS on a protein called PTP1B.  Tonks discovered PTP1B some 25 years ago. It is an enzyme – one in a family of protein tyrosine phosphatases (PTPs), of which there are 105 in humans -- that performs the essential biochemical task of removing phosphate groups from amino acids called tyrosines in other proteins. Adding and removing phosphates is one of the principal means by which signals are sent among proteins.
 
In cells with oncogenic H-RAS, ROS is produced in small quantities, sufficient to render PTP1B inactive. The team found that with the phosphate-removing enzyme unable to do its usual job, a key protein called AGO2 remains phosphorylated – with the consequence that it can no longer do what it normally does, which is engage the cell’s RNA interference machinery.  In normal cells, the RNAi machinery represses a gene called p21.  But in this specific condition – with H-RAS oncogenically activated, PTP1B inactivated by ROS, and RNAi disabled -- p21 proteins begin to accumulate unnaturally, the team discovered. 
 
“This is the key step – accumulation of p21 proteins effectively halts the cell cycle and enables the cell to enter the senescent state,” explains Ming Yang, a doctoral student in the Tonks lab.  She and Astrid Haase, Ph.D., a postdoctoral investigator in the laboratory of CSHL Professor Greg Hannon, are the first two authors, respectively, on the team’s paper, published in Molecular Cell.
 
“This is confirmation of a hypothesis we presented five years ago,” Tonks says.  “We knew that oncogenic RAS induced the production of ROS. We proposed that this would lead to regulation of PTPs, and using the example of PTP1B this is precisely what the team discovered in this work – showing also how inactivation of this PTP is part of a complex signaling cascade that can culminate in the induction of senescence.”
 
ROS have been linked to the pathogenesis of several diseases including Alzheimer's, diabetes and heart failure. “By showing that PTP1B inactivation by oxidation prevents AGO2 from doing its job, we make a clear link between ROS and gene silencing which could also be observed in other pathologies” says Boivin. Hence, the role of PTP1B in keeping the RNAi machinery active could have important ramifications. 
 
Entering senescence is not enough to arrest oncogenesis completely.  Oncogenic mutations typically multiply as cancers evolve to promote their survival and proliferation.  But the current work does show the potential importance of knowing the genetic background of a cancer patient, for there are windows of time – narrow though they may be – in which naturally occurring processes induce pauses in growth.  
 
Funders of the research described here include: National Institutes of Health grants CA53840 and GM55989, and S10RR027990 and P30CA016087; CSHL Cancer Center Support Grant; Joni Gladowsky Breast Cancer Foundation; the Don Monti Memorial Research Foundation; The Irving A. Hansen Memorial Foundation; West Islip Breast Cancer Coalition for Long Island; Glen Cove CARES; Find A Cure Today (FACT); Constance Silveri; Robertson Research Fund; and Masthead Cove Yacht Club Carol Marcincuk Fund; Fonds de Recherche de l'Institut de Cardiologie de Montréal; Heart and Stroke Foundation-Québec.
 
Additional funders of research in the Tonks Lab at CSHL include: Aboff’s Inc.; Hearts for Cancer; Islip Breast Cancer Coalition; Jo-Ellen and Ira Hazan; Panera Bread; Fannie E. Rippel Foundation; Judi Shesh Memorial Foundation; Mary F. Smith Foundation; Caroline Bassett; The WTFC Organization, Inc.
 
“Dephosphorylation of Tyrosine 393 in Argonaute 2 by Protein Tyrosine Phosphatase 1B Regulates Gene Silencing in Oncogenic RAS-Induced Senescence” appears online in Molecular Cell August 28, 2014. The authors are: Ming Yang, Astrid D. Haase, Fang-Ke Huang, Gerald Coulis, Keith D. Rivera, Bryan C. Dickinson, Christopher J. Chang, Darryl J. Pappin, Thomas A. Neubert, Gregory J. Hannon, Benoit Boivin and Nicholas K. Tonks. The paper can be obtained here.
 
About Cold Spring Harbor Laboratory
Founded in 1890, Cold Spring Harbor Laboratory (CSHL) has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. CSHL is ranked number one in the world by Thomson Reuters for the impact of its research in molecular biology and genetics. The Laboratory has been home to eight Nobel Prize winners. Today, CSHL's multidisciplinary scientific community is more than 600 researchers and technicians strong and its Meetings & Courses program hosts more than 12,000 scientists from around the world each year to its Long Island campus and its China center. For more information, visit cshl.edu.
 
PicturedWhen the oncogene H-RAS is activated in a cell (right panel), the cell begins to produce hydrogen peroxide (tagged with a red fluorescent marker), a form of reactive oxygen species. It's the first step in a signaling cascade that culminates in the cell entering, at least for a time, a quiescent, self-protective state called senescence. In the control, at left, RAS is not oncogenic.
Photos

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