16 CFR 460.15 - How installers must handle fact sheets.

Science.gov (United States)

2010-01-01

... ADVERTISING OF HOME INSULATION § 460.15 How installers must handle fact sheets. If you are an installer, you... from you, you must show them the fact sheet(s) for the type(s) of insulation they want. You can decide...

Best Management Practice, Fact Sheet 2. Sheet Flow to Open Space

OpenAIRE

Sample, David; Doumar, Lia

2013-01-01

This publication explains what sheet flow to open space is, where and how it is used, their limitations, routine and nonroutine maintenance, expected costs, and a glossary of terms. This fact sheet is one of a 15-part series on urban stormwater management practices.

2012 Swimming Season Fact Sheets

Science.gov (United States)

To help beachgoers make informed decisions about swimming at U.S. beaches, EPA annually publishes state-by-state data about beach closings and advisories for the previous year's swimming season. These fact sheets summarize that information by state.

16 CFR 460.13 - Fact sheets.

Science.gov (United States)

2010-01-01

... INSULATION § 460.13 Fact sheets. If you are a manufacturer, you must give retailers and installers fact... uses. (b) A heading: “This is ____ insulation.” Fill in the blank with the type and form of your... compressed during installation.” (e) After the chart and any statement dealing with the specific type of...

Creutzfeldt-Jakob Disease Fact Sheet for Healthcare Workers and Morticians

Science.gov (United States)

... here Home » Disorders » Patient & Caregiver Education » Fact Sheets Creutzfeldt-Jakob Disease Fact Sheet for Healthcare Workers and Morticians Creutzfeldt-Jakob disease (CJD) is a rare, fatal brain disorder that ...

Clean Cities Fact Sheet

Energy Technology Data Exchange (ETDEWEB)

2004-01-01

This fact sheet explains the Clean Cities Program and provides contact information for all coalitions and regional offices. It answers key questions such as: What is the Clean Cities Program? What are alternative fuels? How does the Clean Cities Program work? What sort of assistance does Clean Cities offer? What has Clean Cities accomplished? What is Clean Cities International? and Where can I find more information?

Autism: General Information. Fact Sheet Number 1 = Autismo: Informacion General. Fact Sheet Number 22.

Science.gov (United States)

Interstate Research Associates, McLean, VA.

This fact sheet on autism is offered in both English and Spanish, and is the same in both languages although numbered differently. It provides a definition, information on incidence, typical characteristics, and educational implications. It notes that autism is listed as a separate category under the Individuals with Disabilities Education Act.…

75 FR 24740 - Recovery Fact Sheet RP9580.102, Permanent Relocation

Science.gov (United States)

2010-05-05

... DEPARTMENT OF HOMELAND SECURITY Federal Emergency Management Agency [Docket ID FEMA-2010-0028] Recovery Fact Sheet RP9580.102, Permanent Relocation AGENCY: Federal Emergency Management Agency, DHS... Management Agency (FEMA). DATES: This fact sheet is effective April 14, 2010. ADDRESSES: This final fact...

Nanotechnology for Site Remediation: Fact Sheet

Science.gov (United States)

This fact sheet presents a snapshot of nanotechnology and its current uses in remediation. It presents information to help site project managers understand the potential applications of this group of technologies at their sites.

HIV/AIDS Clinical Trials Fact Sheet

Science.gov (United States)

... AIDS Drugs Clinical Trials Apps skip to content HIV Overview Home Understanding HIV/AIDS Fact Sheets HIV/ ... 4 p.m. ET) Send us an email HIV/AIDS Clinical Trials Last Reviewed: August 25, 2017 ...

Catalog of CERCLA applicable or relevant and appropriate requirements (ARARs) - fact sheets

Energy Technology Data Exchange (ETDEWEB)

1990-07-01

Section 121(d) of the Comprehensive Environmental Response Compensation and Liability Act (CERCLA) as amended by the Superfund Amendments and Reauthorization Act of 1986 (SARA), requires attainment of federal and state applicable or relevant and appropriate requirements (ARARs). Subpart E, Section 300.400(g) {open_quotes}Identification of applicable or relevant and appropriate requirements{close_quotes} of the National Oil and Hazardous Substances Pollution Contingency Plan (NCP)(55 FR 8666, March 8, 1990) describes the process for attaining ARARs. The purpose of this catalog is to provide DOE Program Offices and Field Organizations with all of the {open_quotes}Quick Reference Fact Sheets{close_quotes} on attaining ARARS. These fact sheets provide overviews of ARARs for CERCLA cleanup actions pertinent to DOE environmental restoration activities. All of the fact sheets in this catalog were prepared by the Environmental Protection Agency`s Office of Solid Waste and Emergency Response. Fact sheets 1-7 discuss land disposal restrictions (LDRs) and their applicability. LDRs may pertain to a number of CERCLA response actions at DOE facilities. Fact Sheets 8-13 are based on the CERCLA Compliance with Other Laws Manual: Parts I and II and provide an overview of many other CERCLA ARARs. Overview of ARARs-Focus on ARAR Waivers (fact sheet 11), provides a good introduction to ARARS. The last two fact sheets, 14 and 15, are periodic reports that describe additional fact sheets and clarify issues.

Epilepsy: General Information. Fact Sheet Number 6 = La Epilepsia: Informacion General. Fact Sheet Number 20.

Science.gov (United States)

Interstate Research Associates, McLean, VA.

This fact sheet on epilepsy is offered in both English and Spanish. It provides a definition, information on incidence, typical characteristics, and educational implications. It notes that epilepsy is classified as "other health impaired" under the Individuals with Disabilities Education Act and that students with epilepsy are eligible for special…

Biomolecular Science (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2012-04-01

A brief fact sheet about NREL Photobiology and Biomolecular Science. The research goal of NREL's Biomolecular Science is to enable cost-competitive advanced lignocellulosic biofuels production by understanding the science critical for overcoming biomass recalcitrance and developing new product and product intermediate pathways. NREL's Photobiology focuses on understanding the capture of solar energy in photosynthetic systems and its use in converting carbon dioxide and water directly into hydrogen and advanced biofuels.

Spina Bifida. Fact Sheet = Espina Bifida. Hojas Informativas Sobre Discapacidades.

Science.gov (United States)

National Information Center for Children and Youth with Disabilities, Washington, DC.

This fact sheet offers definitions of the three types of spina bifida (spina bifida occulta, meningocele, and myelomeningocele), outlines their incidence, describes characteristics of individuals with spina bifida, and reviews educational implications. The fact sheet discusses the need for many children with myelomeningocele to learn to manage…

Supporting Documentation for the 2008 Update to the Insulation Fact Sheet

Energy Technology Data Exchange (ETDEWEB)

Stovall, Therese K [ORNL

2008-02-01

The Insulation Fact Sheet provides consumers for general guidance and recommended insulation levels for their home. This fact sheet has been on-line since 1995 and this update addresses new insulation materials, as well as updated costs for energy and materials.

75 FR 13777 - Disaster Assistance Fact Sheet DAP9580.107, Child Care Services

Science.gov (United States)

2010-03-23

...] Disaster Assistance Fact Sheet DAP9580.107, Child Care Services AGENCY: Federal Emergency Management Agency... (FEMA) is providing notice of the availability of the final Disaster Assistance Fact Sheet DAP9580.107...'s Web site at http://www.fema.gov . You may also view a hard copy of the fact sheet at the Office of...

Photovoltaics Fact Sheet

Energy Technology Data Exchange (ETDEWEB)

None

2016-02-01

This fact sheet is an overview of the Photovoltaics (PV) subprogram at the U.S. Department of Energy SunShot Initiative. The U.S. Department of Energy (DOE)’s Solar Energy Technologies Office works with industry, academia, national laboratories, and other government agencies to advance solar PV, which is the direct conversion of sunlight into electricity by a semiconductor, in support of the goals of the SunShot Initiative. SunShot supports research and development to aggressively advance PV technology by improving efficiency and reliability and lowering manufacturing costs. SunShot’s PV portfolio spans work from early-stage solar cell research through technology commercialization, including work on materials, processes, and device structure and characterization techniques.

Advancing Concentrating Solar Power Research (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

None, None

2014-02-01

Researchers at the National Renewable Energy Laboratory (NREL) provide scientific, engineering, and analytical expertise to help advance innovation in concentrating solar power (CSP). This fact sheet summarizes how NREL is advancing CSP research.

Fact Sheets: Air Toxics Rules for the Manufacture of Amino/Phenolic Resins

Science.gov (United States)

This page contains a December 1999 fact sheet for the proposed National Emission Standards for Hazardous Air Pollutants (NESHAP): Manufacture of Amino/Phenolic Resins and a September 2014 fact sheet with information regarding the final NESHAP

Spina Bifida: General Information. Fact Sheet Number 12 = La Espina Bifida: Informacion General. Fact Sheet Number 21.

Science.gov (United States)

Interstate Research Associates, McLean, VA.

This fact sheet on spina bifida is offered in both English and Spanish. It provides definitions of the three types of spina bifida (spina bifida occulta, meningocele, and myelomeningocele). Incidence figures are given as are typical characteristics of children with spina bifida. Educational implications are briefly noted, including the need to…

Hispanics/Latinos & Cardiovascular Disease: Statistical Fact Sheet

Science.gov (United States)

Statistical Fact Sheet 2013 Update Hispanics/Latinos & Cardiovascular Diseases Cardiovascular Disease (CVD) (ICD/10 codes I00-I99, Q20-Q28) (ICD/9 codes 390-459, 745-747)  Among Mexican-American adults age 20 ...

College Experience and Volunteering. Fact Sheet

Science.gov (United States)

Marcelo, Karlo Barrios

2007-01-01

College experience and volunteering are positively correlated. Measurable differences in civic activity exist between young people who attend college and young people who do not. This fact sheet explores volunteering as civic engagement among youth with college experience, ages 19-25, which was down for the second year in a row in 2006. The…

Large Fleets Lead in Petroleum Reduction (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

Proc, H.

2011-03-01

Fact sheet describes Clean Cities' National Petroleum Reduction Partnership, an initiative through which large private fleets can receive support from Clean Cities to reduce petroleum consumption.

Chemical Data Reporting Fact Sheet: Chemicals Snapshot

Science.gov (United States)

This fact sheet provides a brief overview of the chemical manufacturing, processing, and use information collected for the 2012 Chemical Data Reporting (CDR) rule. Users do not have access to the complete CDR data set and should draw conclusions with care.

Cerebral Palsy. Fact Sheet = La Paralisis Cerebral. Hojas Informativas Sobre Discapacidades.

Science.gov (United States)

National Information Center for Children and Youth with Disabilities, Washington, DC.

This fact sheet on cerebral palsy is written in both English and Spanish. First, it provides a definition of cerebral palsy and considers various causes (e.g., an insufficient amount of oxygen reaching the fetal or newborn brain). The fact sheet then offers incidence figures and explains characteristics of the three main types of cerebral palsy:…

World War II Informational Fact Sheets.

Science.gov (United States)

Department of Defense, Washington, DC.

This commemorative book provides numerous fact sheets on various aspects of World War II, both on the fighting front and the homefront. Replicas of posters of the war era, descriptions of battles with maps, contributions of women and minorities to the war effort, even music of the wartime era, add to this collection of resource materials useful to…

Vietnamese Hurricane Response Fact Sheets

Science.gov (United States)

Các tờ dữ kiện được cung cấp nơi đây mô tả vai trò của EPA trong việc đáp ứng với bão và cách các chương trình cụ thể cung cấp sự hỗ trợ. The Vietnamese fact sheets provided here describe EPA's role in a hurricane response.

Are we reaching the target audience? Evaluation of a fish fact sheet.

Science.gov (United States)

Burger, J; Waishwell, L

2001-09-28

According to the US Environmental Protection Agency, over 16% of freshwater lakes and 7% of the rivers are under some sort of fish consumption advisory because of the presence of toxic chemicals. There is considerable interest in the issuing of information, advisories, and fact sheets concerning the consumption of wild-caught fish from contaminated waters, and in the actual consumption patterns of subsistence and recreational anglers. Despite the large number of consumption advisories issued by state agencies, there is little information on how these advisories, or other forms of risk communication, are perceived by target audiences, notably fishermen and women of child-bearing age. The states of South Carolina and Georgia issue consumption advisories for fish from the Savannah River, among other sites. To gain a greater insight into the perception of anglers about a supplemental fish fact sheet jointly developed by South Carolina, Georgia, federal agencies, and the Consortium for Risk Evaluation with Stakeholder Participation, we interviewed fisherman along the Savannah River. The objectives were to determine: (1) whether they had previously read the Fish Fact Sheet or had heard about the consumption advisories; (2) what major message they obtained from the sheet; (3) who they felt the fact sheet was aimed at, and who should get the Fish Fact Sheet; (4) who should be concerned about health risks from consuming the fish; and (5) the best method of disseminating such information. We interviewed 92 fishermen (37% black, 62% white) during the fishing season of 1999. Half had heard some information about consumption advisories, mainly from the media (64%). The study concluded that there were no ethnic differences in whether they had heard about the advisories, understood the major message of the fact sheet, felt they could reduce their risk from consuming the fish, or felt that it made a difference which agency issued the fact sheet. There were significant ethnic

Renewable Energy Project Development Assistance (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2013-07-01

This fact sheet provides information on the Tribes selected to receive assistance from the U.S. Department of Energy Office of Indian Energy 2013 Strategic Technical Assistance Response Team (START) Program, which provides technical expertise to support the development of next-generation energy projects on tribal lands.

Down Syndrome: General Information. Fact Sheet Number 4 = El Sindrome de Down: Informacion General. Fact Sheet Number 15.

Science.gov (United States)

Interstate Research Associates, McLean, VA.

This fact sheet on Down Syndrome is offered in both English and Spanish. First it provides a definition and description of this syndrome, noting its etiology in a chromosomal abnormality. Incidence figures are then given. Typical characteristics of people with Down Syndrome are listed. Commonly associated health-related problems are noted,…

Canada and the Kyoto Protocol: Fact Sheet No. 5 - Developing countries

International Nuclear Information System (INIS)

2000-11-01

This fact sheet acknowledges that global change affects developed and developing countries alike, and the fact that most developing countries do not have the human, financial and technical capacity to effectively address climate change issues without help from the industrialized nations. The fact sheet also puts Canada on record as being in agreement with the spirit of the Kyoto Protocol to encourage the participation of developing countries in global efforts to combat climate change and promote sustainable development and reaffirms Canada's willingness to provide financial and technical assistance to developing countries to enable them to play a meaningful part in this global effort. In this context, the fact sheet briefly describes the new Canada Climate Change Development Fund which has been set up to reduce the growth of GHG emissions and support carbon sink activities in developing countries, to strengthen the capacity of developing conuntries to reduce their vulnerability to adverse effects of climate change, and to participate in global efforts to combat them

TSCA Chemical Data Reporting Fact Sheet: Imported Articles

Science.gov (United States)

This fact sheet provides guidance and sample reporting scenarios on the reporting exemption for the import of a chemical substance as part of an article, for purposes of the Chemical Data Reporting (CDR) rule.

Toxicity of Pesticides. Agrichemical Fact Sheet 2.

Science.gov (United States)

Hock, Winand K.

This fact sheet gives the acute oral and dermal toxicity (LD 50) of over 250 pesticides in lab animals. The chemicals are categorized as fungicides, herbicides, insecticides, or miscellaneous compounds. One or more trade names are given for each pesticide. In addition, a brief explanation of toxicity determination is given. (BB)

Soft Costs Fact Sheet

Energy Technology Data Exchange (ETDEWEB)

None

2016-05-01

This fact sheet is an overview of the systems integration subprogram at the U.S. Department of Energy SunShot Initiative. Soft costs can vary significantly as a result of a fragmented energy marketplace. In the U.S., there are 18,000 jurisdictions and 3,000 utilities with different rules and regulations for how to go solar. The same solar equipment may vary widely in its final installation price due to process and market variations across jurisdictions, creating barriers to rapid industry growth. SunShot supports the development of innovative solutions that enable communities to build their local economies and establish clean energy initiatives that meet their needs, while at the same time creating sustainable solar market conditions.

77 FR 40626 - RP9580.210, Personal Assistance Services in Shelters Fact Sheet

Science.gov (United States)

2012-07-10

... DEPARTMENT OF HOMELAND SECURITY Federal Emergency Management Agency [Docket ID FEMA-2012-0014] RP9580.210, Personal Assistance Services in Shelters Fact Sheet AGENCY: Federal Emergency Management... Management Agency (FEMA) is accepting comments on Recovery Fact Sheet RP9580.210, Personal Assistance...

SunShot Initiative Fact Sheet

Energy Technology Data Exchange (ETDEWEB)

DOE Solar Energy Technologies Office

2015-04-01

The U.S. Department of Energy (DOE) SunShot Initiative is a collaborative national effort launched in 2011 that aggressively drives innovation to make solar energy fully cost competitive with traditional energy sources before the end of the decade. The SunShot fact sheet outlines goals and successes of the program as it works with private companies, universities, non-profit organizations, state and local governments, and national laboratories to drive down the cost of solar electricity to $0.06 per kilowatt-hour, without incentives, by the year 2020.

TSCA Chemical Data Reporting Fact Sheet: Articles

Science.gov (United States)

This fact sheet provides guidance on classifying articles under the Toxic Substances Control Act (TSCA) and determining the applicability of EPA’s articles exclusion policy for purposes of the Chemical Data Reporting (CDR) rule. The primary goal of this document is to help the regulated community comply with the requirements of the CDR rule.

SunShot Catalyst Prize Competition Fact Sheet

Energy Technology Data Exchange (ETDEWEB)

Solar Energy Technologies Office

2015-04-01

This fact sheet is an overview of the Catalyst Energy Innovation Prize, an open innovation program launched in 2014 by the U.S. Department of Energy SunShot Initiative. This program aims to catalyze the rapid creation and development of products and solutions that address near-term challenges in the U.S. solar energy marketplace.

Careers "Fact Sheets" for clinical engineering & biomedical technology.

Science.gov (United States)

Pacela, A F

1991-01-01

Three Careers "Fact Sheets" include information on CE and BMET job titles, job descriptions, and certification. These materials are intended to aid in furthering professional recognition for Clinical Engineers and BMETs, and may be useful in communicating with Administration or Human Resources departments.

Systems Integration Fact Sheet

Energy Technology Data Exchange (ETDEWEB)

None

2016-06-01

This fact sheet is an overview of the Systems Integration subprogram at the U.S. Department of Energy SunShot Initiative. The Systems Integration subprogram enables the widespread deployment of safe, reliable, and cost-effective solar energy technologies by addressing the associated technical and non-technical challenges. These include timely and cost-effective interconnection procedures, optimal system planning, accurate prediction of solar resources, monitoring and control of solar power, maintaining grid reliability and stability, and many more. To address the challenges associated with interconnecting and integrating hundreds of gigawatts of solar power onto the electricity grid, the Systems Integration program funds research, development, and demonstration projects in four broad, interrelated focus areas: grid performance and reliability, dispatchability, power electronics, and communications.

General Information about Learning Disabilities (Fact Sheet Number 7) = Informacion General sobre Impedimentos en el Aprendizaje (Fact Sheet Number 19).

Science.gov (United States)

Interstate Research Associates, Inc., Washington, DC.

This fact sheet providing general information about learning disabilities is presented in both English and Spanish versions. It begins with the federal definition of learning disabilities and a discussion of its implications followed by estimates of incidence. Typical characteristics of students with learning disabilities are then summarized as…

Final Rule for Industrial Process Cooling Towers: Fact Sheet

Science.gov (United States)

Fact sheet concerning a final rule to reduce air toxics emissions from industrial process cooling towers. Air toxics are those pollutants known or suspected of causing cancer or other serious health effects.

Facts about food irradiation. A series of fact sheets from the International Consultative Group on Food Irradiation

Energy Technology Data Exchange (ETDEWEB)

NONE

1991-12-01

The safety and benefits of foods processed by ionizing radiation are well documented. In an effort to provide governments, especially those of developing countries, with scientifically accurate information on issues of general interest to the public, the International Consultative Group on Food Irradiation (ICGFI), which was established under the aegis of the Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO), and the IAEA, decided at its 7th Annual Meeting in Rome, Italy, on October 1990, to issue a series of ''Fact Sheets'' on the subject. ICGFI, an inter-governmental body with a membership of 37 governments, has as one of its mandates the function to provide information to Member States of the FAO, WHO, and IAEA and to the three organizations themselves on the safe and proper use of food irradiation technology. The Fact Sheets included here cover issues relating to: status and trends; scientific and technical terms; food irradiation and radioactivity; chemical changes in irradiated food; nutritional quality of irradiated foods; genetic studies; microbiological safety of irradiated food; irradiation and food safety; irradiation and food additives and residues; packaging of irradiated foods; safety of irradiation facilities; controlling the process; food irradiation costs; and irradiated foods and the consumer. The Fact Sheets have been separately indexed and included in the INIS Database under Reference Numbers 23011206-23011217, 23011319 and 23012743. The Fact Sheets were first issued by the ICGFI Secretariat (Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, Vienna, Austria) in May 1991.

Facts about food irradiation. A series of fact sheets from the International Consultative Group on Food Irradiation

International Nuclear Information System (INIS)

1991-12-01

The safety and benefits of foods processed by ionizing radiation are well documented. In an effort to provide governments, especially those of developing countries, with scientifically accurate information on issues of general interest to the public, the International Consultative Group on Food Irradiation (ICGFI), which was established under the aegis of the Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO), and the IAEA, decided at its 7th Annual Meeting in Rome, Italy, on October 1990, to issue a series of ''Fact Sheets'' on the subject. ICGFI, an inter-governmental body with a membership of 37 governments, has as one of its mandates the function to provide information to Member States of the FAO, WHO, and IAEA and to the three organizations themselves on the safe and proper use of food irradiation technology. The Fact Sheets included here cover issues relating to: status and trends; scientific and technical terms; food irradiation and radioactivity; chemical changes in irradiated food; nutritional quality of irradiated foods; genetic studies; microbiological safety of irradiated food; irradiation and food safety; irradiation and food additives and residues; packaging of irradiated foods; safety of irradiation facilities; controlling the process; food irradiation costs; and irradiated foods and the consumer. The Fact Sheets have been separately indexed and included in the INIS Database under Reference Numbers 23011206-23011217, 23011319 and 23012743. The Fact Sheets were first issued by the ICGFI Secretariat (Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, Vienna, Austria) in May 1991

Epilepsy. Fact Sheet = Epilepsia. Hojas Informativas Sobre Discapacidades.

Science.gov (United States)

National Information Center for Children and Youth with Disabilities, Washington, DC.

This fact sheet, written in both English and Spanish, provides a definition, information on incidence, typical characteristics, and educational implications of epilepsy. It notes that epilepsy is classified as "other health impaired" under the Individuals with Disabilities Education Act (IDEA) and that children with epilepsy or seizure disorders…

OPA Q's and A's: Overview of the Oil Pollution Act of 1990. Fact sheet

International Nuclear Information System (INIS)

1991-12-01

The OPA Q's and A's are part of a series of fact sheets that provide up-to-date information on EPA's implementation of the OPA. The first fact sheet provides an overview of the various provisions of the OPA and the Agency's responsibilities under the new law

Teenage Pregnancy. Highlights: An ERIC/CAPS Fact Sheet.

Science.gov (United States)

Lachance, Laurie L.

This fact sheet addresses the issue of teenage pregnancy. Six factors contributing to the current attention focused on teenage pregnancy and parenthood are listed and teenage pregnancy and birth rates are discussed. Other areas covered include teenage nonuse of contraception, sex education by schools and parents, family planning services, and the…

Energy-Saving Opportunities for Manufacturing Companies, International Fact Sheet (Spanish)

Energy Technology Data Exchange (ETDEWEB)

2010-08-01

This English/Spanish fact sheet describes the Industrial Technologies Program Save Energy Now model and provides information on tools and resources to help manufacturing facilities reduce industrial energy intensity.

Participation in Sports and Civic Engagement. Fact Sheet

Science.gov (United States)

Lopez, Mark Hugo; Moore, Kimberlee

2006-01-01

One reason to offer sports in school is to teach youth the values, skills, and habits that will make them more active, engaged, and responsible citizens. Past evidence on the civic effects of sports is mixed, but points to some potential positive civic effects. This fact sheet uses recent data from the 2002 National Youth Survey of Civic…

Supporting documentation for the 1997 revision to the DOE Insulation Fact Sheet

Energy Technology Data Exchange (ETDEWEB)

Stovall, T.K.

1997-08-22

The Department of Energy (DOE) Insulation Fact Sheet has been revised to reflect developments in energy conservation technology and the insulation market. A nationwide insulation cost survey was made by polling insulation contractors and builders, and the results are reported here. These costs, along with regional weather data, regional fuel costs, and fuel-specific system efficiencies were used to produce recommended insulation levels for new and existing houses. This report contains all of the methodology, algorithms, assumptions, references, and data resources that were used to produce the 1997 DOE Insulation Fact Sheet.

CMS fact sheet : to give an overview of the basic facts on the CMS Detector, its aims and collaboration

CERN Multimedia

CMS, Outreach

2010-01-01

2-sided color print A4 size sheet containing the facts on the CMS Detector, its name, what it is designed to do, questions scientists hope to answer, collaboration members, detector parts and their functions, and other miscellaneous facts on the CMS detector

Child Care in Sweden. Fact Sheets on Sweden.

Science.gov (United States)

Swedish Inst., Stockholm.

This fact sheet outlines Sweden's policies of government-supported child care and parental insurance provisions. Swedish families receive: (1) free maternity and child health care; (2) child allowances for each child of 9,000 krona per year through age 16; (3) up to 450 days of paid parental leave for the birth of a child, with 360 days paid at 90…

State Arts Agency Fact Sheet: Support for Arts Education

Science.gov (United States)

Online Submission, 2015

2015-01-01

This national overview of state arts agency grants and services for arts education includes summary statistics and geographic distribution. The fact sheet uses data from Final Descriptive Reports of state arts agency grant-making activities submitted annually to the National Assembly of State Arts Agencies (NASAA) and the National Endowment for…

Fact Sheet: What Parents Need to Know About Zika Virus

Science.gov (United States)

... Management Post-Disaster Child Care Resources ACF Capabilities Policies Resources You are here ACF Home › Office of Human Services Emergency Preparedness and Response › Resource Library › Fact Sheet: What Parents Need to Know About ...

75 FR 45144 - Recovery Fact Sheet 9580.203, Debris Monitoring

Science.gov (United States)

2010-08-02

... DEPARTMENT OF HOMELAND SECURITY Federal Emergency Management Agency [Docket ID FEMA-2010-0045] Recovery Fact Sheet 9580.203, Debris Monitoring AGENCY: Federal Emergency Management Agency, DHS. ACTION: Notice of availability; request for comments. SUMMARY: The Federal Emergency Management Agency (FEMA) is...

75 FR 33821 - Recovery Fact Sheet RP9580.205, Public Assistance Funding to Public Housing Facilities

Science.gov (United States)

2010-06-15

... Emergency Management Agency (FEMA) is providing notice of the availability of the final Recovery Fact Sheet... the fact sheet at the Office of Chief Counsel, Federal Emergency Management Agency, Room 835, 500 C... DEPARTMENT OF HOMELAND SECURITY Federal Emergency Management Agency [Docket ID FEMA-2010-0034...

Clean Energy Solutions Center Services (Vietnamese Translation) (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2014-11-01

This is the Vietnamese language translation of the Clean Energy Solutions Center (Solutions Center) fact sheet. The Solutions Center helps governments, advisors and analysts create policies and programs that advance the deployment of clean energy technologies. The Solutions Center partners with international organizations to provide online training, expert assistance, and technical resources on clean energy policy.

Clean Energy Solutions Center Services (Arabic Translation) (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2014-06-01

This is the Arabic translation of the Clean Energy Solutions Center Services fact sheet. The Clean Energy Solutions Center (Solutions Center) helps governments, advisors and analysts create policies and programs that advance the deployment of clean energy technologies. The Solutions Center partners with international organizations to provide online training, expert assistance, and technical resources on clean energy policy.

African American Students and U.S. High Schools. Fact Sheet

Science.gov (United States)

Alliance for Excellent Education, 2008

2008-01-01

This fact sheet highlights the statistics of the status of the African American students living in the continental United States in terms of: population; graduation, dropouts, and preparedness; schools, segregation, and teacher quality; and special, gifted, and college preparatory education. According to the National Center for Education…

Fact sheet on thyroid test in Fukushima prefecture

International Nuclear Information System (INIS)

Hiranuma, Yuri

2017-01-01

Fukushima Prefecture chose about 360,000 people who were 18 years old or younger at the time of the accident at Fukushima Daiichi NPS on March 11, 2011, and started thyroid test as part of the prefectural health survey on October 9, 2011. The survey is entrusted to Fukushima Medical University of Medicine from Fukushima Prefecture. This fact sheet summarizes the current state of thyroid test in Fukushima Prefecture. A considerable amount of data and related information have been accumulated in the seventh year from the beginning. However, especially the information disclosed in English by people concerned combined the results of the second round, which was not analyzed properly, with those of the first round. This fact gives a suspicion of intention to deny the possibility of radiation influence in such a way as to make it invisible even if there was the influence. This study firstly prepared an English fact sheet to convey the actual situation in English. However, since some official information/views were contained in papers only available in English, this study also prepared the Japanese version for enabling to grasp the current situation. The Japanese version is supplemented with explanation rather than the Japanese translation of the English version, in order to make it easier to understand. The future of thyroid test is a topic that is causing controversy. Now that the transparency, scientific fairness, and the data integrity of Fukushima Medical University are suspected, it is extremely important that an independent analysis in the true sense is to be performed by qualified experts based on the latest evidence. (A.O.)

Fact Sheet: Alternative Low-Sulfur Diesel Fuel Transition Program for Alaska

Science.gov (United States)

This fact sheet summarizes EPA's final rule modifying the diesel fuel regulations to apply an effective date of 6-1-2010 for 15 ppm sulfur requirements for highway, nonroad, locomotive and marine diesel fuel produced/imported for, distributed

Drinking water regulations under the Safe Drinking Water Act. Fact sheet

International Nuclear Information System (INIS)

1990-12-01

The fact sheet describes the requirements covered under the 1986 amendments to the Safe Drinking Water Act. Levels of various contaminants (including radio nuclides) are explained. Also discussed are the Surface Water Treatment Rule and the Total Coliforms Rule

Delinquency Cases in Juvenile Court, 2002. OJJDP Fact Sheet #02

Science.gov (United States)

Stahl, Anne L.

2006-01-01

This fact sheet presents statistics on delinquency cases processed by juvenile courts in 2002. The number of delinquency cases handled by juvenile courts decreased 11 percent between 1997 and 2002. During this time, the number of person offense cases decreased 2 percent, property offense cases decreased 27 percent, drug law violation cases…

Juvenile Delinquency Probation Caseload, 1985-2002. OJJDP Fact Sheet #04

Science.gov (United States)

Livsey, Sarah

2006-01-01

This fact sheet presents statistics on delinquency cases resulting in probation, 2002. Probation was the disposition in 38 percent of all delinquency cases processed by the juvenile courts in 2002. The number of cases placed on probation increased 44 percent between 1985 and 2002. Property offense cases made up the greatest proportion of the…

EERE-Supported International Activities in Latin America (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2010-05-01

The Office of Energy Efficiency and Renewable Energy (EERE) is involved in a variety of international initiatives, partnerships, and events that promote greater understanding and use of renewable energy (RE) and energy efficiency (EE) worldwide. In support of the Energy and Climate Partnership of the Americas (ECPA), EERE is working with several Latin American countries to advance EE and RE deployment for economic growth, energy security, poverty relief, and disaster recovery goals. This fact sheet highlights those activities.

Fact Sheets and Questions and Answers for the Final Air Toxics Rules for the Aerospace Manufacturing and Rework Industry

Science.gov (United States)

This page contains the July 1995 final rule fact sheet and the January 2015 proposed rule fact sheet that contains information on the National Emission Standards for Aerospace Manufacturing and Rework Facilities, as well as a 2001 Q&A document on the rule

Fact sheet: National primary drinking water regulations for lead and copper

International Nuclear Information System (INIS)

1991-05-01

The Fact Sheet contains a summary of what the regulations will do, establish, and provide; regulatory impact in regards to benefits and costs; treatment technique requirements; tap water monitoring for lead and copper; water quality monitoring (other than lead and copper); monitoring schedules, regulatory schedules for large, medium-sized, and small systems

Fact Sheet - Final Air Toxics Rule for Gold Mine Ore Processing and Production

Science.gov (United States)

Fact sheet summarizing main points of National Emissions Standards for Hazardous Air Pollutants for gold ore processing and production facilities, the seventh largest source of mercury air emission in the United States.

Human Trafficking of Children in the United States: A Fact Sheet

Science.gov (United States)

US Department of Education, 2007

2007-01-01

This fact sheet presents questions and answers related to the human trafficking of children in the United States. It describes human trafficking and its extent in the United States, how human traffickers target children for coerced labor and sex exploitation, how to identify victims of human trafficking, how to report a suspected incidence of…

Framework for DOE mixed low-level waste disposal: Site fact sheets

Energy Technology Data Exchange (ETDEWEB)

Gruebel, M.M.; Waters, R.D.; Hospelhorn, M.B.; Chu, M.S.Y. [eds.

1994-11-01

The Department of Energy (DOE) is required to prepare and submit Site Treatment Plans (STPS) pursuant to the Federal Facility Compliance Act (FFCAct). Although the FFCAct does not require that disposal be addressed in the STPS, the DOE and the States recognize that treatment of mixed low-level waste will result in residues that will require disposal in either low-level waste or mixed low-level waste disposal facilities. As a result, the DOE is working with the States to define and develop a process for evaluating disposal-site suitability in concert with the FFCAct and development of the STPS. Forty-nine potential disposal sites were screened; preliminary screening criteria reduced the number of sites for consideration to twenty-six. The DOE then prepared fact sheets for the remaining sites. These fact sheets provided additional site-specific information for understanding the strengths and weaknesses of the twenty-six sites as potential disposal sites. The information also provided the basis for discussion among affected States and the DOE in recommending sites for more detailed evaluation.

Young People and Political Campaigning on the Internet. CIRCLE Fact Sheet.

Science.gov (United States)

Levine, Peter; Lopez, Mark Hugo

2004-01-01

This fact sheet discusses young people and political campaigning on the Internet. It explains how the Internet has become a powerful force in political campaigns. A survey released by the Pew Research Center for the People & the Press on January 11, 2004 found that the Internet is gaining importance as a source of political news, especially for…

Servicios del Centro de Soluciones Para la Energia Limpia (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2014-05-01

This is the Spanish translation of the Clean Energy Solutions Center Services fact sheet. The Clean Energy Solutions Center (Solutions Center) helps governments, advisors and analysts create policies and programs that advance the deployment of clean energy technologies. The Solutions Center partners with international organizations to provide online training, expert assistance, and technical resources on clean energy policy.

Fact Sheet- Ancient DNA: What is it? Why is it Important?

OpenAIRE

Alexa Walker; George Nicholas; Daryl Pullman; Alan Goodman; Bioarchaeology and Genetics Working Group

2016-01-01

As genetic research is increasingly applied to new areas of study, including in archaeological and heritage contexts, a range of questions arise concerning the social, ethical, legal, and political implications of ancient DNA. This fact sheet explains the nature and challenges of aDNA research, and why information from it is important and relevant to people today. 

Fact Sheet: Notice of Ambient Water Quality Criteria Document for Tributyltin (TBT) - Final

Science.gov (United States)

Information pertaining to 2004 Final Acute and Chronic Ambient Aquatic Life Water Quality Criteria for Tributyltin (TBT) for freshwater and saltwater. This fact sheet includes the safe levels of TBT that should protect the majority of species.

NTPR Fact Sheets

Science.gov (United States)

History Documents US Underground Nuclear Test History Reports NTPR Radiation Exposure Reports Enewetak Atoll Cleanup Documents TRAC About Who We Are Our Values History Locations Our Leadership Director Support Center Contact Us FAQ Sheet Links Success Stories Contracts Business Opportunities Current

Questions and Answers about School-Age Children in Self-Care: A Sloan Work and Family Research Network Fact Sheet

Science.gov (United States)

Sloan Work and Family Research Network, 2009

2009-01-01

The Sloan Work and Family Research Network has prepared Fact Sheets that provide statistical answers to some important questions about work-family and work-life issues. This Fact Sheet includes statistics about Children in Self-Care, and answers the following questions about school-age children in self-care: (1) How many school-age children are in…

Systems Performance Analyses of Alaska Wind-Diesel Projects; Kotzebue, Alaska (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

Baring-Gould, I.

2009-04-01

This fact sheet summarizes a systems performance analysis of the wind-diesel project in Kotzebue, Alaska. Data provided for this project include wind turbine output, average wind speed, average net capacity factor, and optimal net capacity factor based on Alaska Energy Authority wind data, estimated fuel savings, and wind system availability.

Fuels planning: science synthesis and integration; social issues fact sheet 08: The "Golden Rule" and other lessons on communicating about hazards

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

Other fact sheets identified considerations for communicating about hazards, talked about the importance of working locally, and discussed the seven laws of effective hazard communication. This fact sheet introduces the "Golden Rule" of hazard communication and shares some final lessons from hazard educators.

Fuels planning: science synthesis and integration; social issues fact sheet 09: Benefits of collaboration

Science.gov (United States)

Christine Esposito

2006-01-01

Wildland fire professionals at the Federal, State, and local levels have a long tradition of collaborating across agencies and jurisdictions to achieve goals that they could not achieve independently. This fact sheet discusses the reasons and resources for collaboration.Other...

Fuels planning: science synthesis and integration; social issues fact sheet 10: Stages of collaboration

Science.gov (United States)

Christine Esposito

2006-01-01

Collaboration is a powerful tool for improving both the management of wildland fire and the overall health of forests and other elements of fire-dependent ecosystems. This fact sheet discusses seven stages that are typical of most collaborations.Other publications in this...

Final Rule to Reduce Hazardous Air Emissions from Newly Built Stationary Combustion Turbines: Fact Sheet

Science.gov (United States)

This page contains an August 2003 fact sheet with information regarding the National Emissions Standards for Hazardous Air Pollutants (NESHAP) for Stationary Combustion Turbines. This document provides a summary of the information for this NESHAP.

Ancient DNA (aDNA): What is it? Why is it important?- Fact Sheet

OpenAIRE

Alexa Walker; George Nicholas; Daryl Pullman; Alan Goodman; Bioarchaeology and Genetics Working Group

2014-01-01

As genetic research is increasingly applied to new areas of study, including in archaeological and heritage contexts, a range of questions arise concerning the social, ethical, legal, and political implications of ancient DNA. This fact sheet explains the nature and challenges of aDNA research, and why information from it is important and relevant to people today.  

TSCA Chemical Data Reporting Fact Sheet: Reporting Manufactured Chemical Substances from Metal Mining and Related Activities

Science.gov (United States)

This fact sheet provides guidance on the Chemical Data Reporting (CDR) rule requirements related to the reporting of mined metals, intermediates, and byproducts manufactured during metal mining and related activities.

Canada and the Kyoto Protocol: Fact Sheet No. 1 - Overview

International Nuclear Information System (INIS)

2000-11-01

This fact sheet outlines the principles underlying Canada's position at the sixth Conference of Parties (COP6) regarding climate change. Capsule descriptions of the Canadian view on carbon sinks (advocating a broader inclusion of sink activities), application of the flexibility mechanisms (the Clean Development Mechanism, Joint Implementation and International Emissions Trading), the issue of compliance (Canada favoring strong incentives to ensure compliance), and strengthening the capacity of developing countries to enhance their contribution to fighting climate change (Canada acknowledging that capacity building and technology transfer needs to be a central part of the global approach to combating climate change)

ATLAS Fact Sheet : To raise awareness of the ATLAS detector and collaboration on the LHC

CERN Multimedia

ATLAS Outreach

2010-01-01

Facts on the Detector, Calorimeters, Muon System, Inner Detector, Pixel Detector, Semiconductor Tracker, Transition Radiation Tracker,, Surface hall, Cavern, Detector, Magnet system, Solenoid, Toroid, Event rates, Physics processes, Supersymmetric particles, Comparing LHC with Cosmic rays, Heavy ion collisions, Trigger and Data Acquisition TDAQ, Computing, the LHC and the ATLAS collaboration. This fact sheet also contains images of ATLAS and the collaboration as well as a short list of videos on ATLAS available for viewing.

Guidelines for Home Energy Upgrade Professionals: Standard Work Specifications for Multifamily Energy Upgrades (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2011-08-01

This fact sheet provides essential information about the 2011 publication of the Workforce Guidelines for Multifamily Home Energy Upgrades, including their origin, their development with the help of industry leaders to create the standard work specifications for retrofit work.

Fuels planning: science synthesis and integration; social issues fact sheet 11: Challenges to collaboration

Science.gov (United States)

Christine Esposito

2006-01-01

Bringing the right people into a collaborative process can be difficult. Potential collaborators must all feel they have something to gain to justify investing resources, sharing knowledge, and perhaps compromising on goals and actions. This fact sheet discusses some of the common challenges that individuals, communities, and institutions face in collaboration.

Technical fact sheets on the impacts of new energy efficiency technologies and measures in ice rinks

Energy Technology Data Exchange (ETDEWEB)

NONE

2003-07-01

This paper presents energy efficiency facts on ice rinks and arenas to advise and inform refrigeration and building professionals. The aim of the paper was to facilitate estimation and compare impacts of various energy efficiency measures and new technologies on the consumption of energy and the reduction of greenhouse gas (GHG) emissions. A computer-based tool modelling ice rink energy consumption was constructed based on DOE-2.1E software. The simulation tool was developed to study the sensitivity of various eco-energetic technologies applied to arenas. Results of the simulations have made it possible to construct 8 facts sheets, including information on simulated heat exchange; calculation of energy consumption for heating and refrigeration; the incorporation of several types of Heating Ventilation and Air Conditioning (HVAC) systems; and to show various strategies of operation. To account for the effects of ice within a building, calculation routines in the form of functional values were added. The model addressed the following parameters: climate; characteristics of the envelope; lighting power and intensity; temperature of the resurfacing water; ice sheet temperature; humidity level of the ice rink; fresh air intake; emissivity index of the ceiling above the ice sheet; refrigeration systems according to type, capacity, output and operation mode; capacity output and operation mode of the air heating system, including heat recovery from the refrigeration system; and capacity, output and operation mode of the domestic and resurfacing hot water heating system, including heat recovery from the refrigeration system. Fact sheets were presented for the type of technology; description; direct or indirect benefits; energy-savings potential; environmental impacts; specific comments from specialists; and a set of charts to facilitate comprehension. tabs., figs.

Fuels planning: science synthesis and integration; economic uses fact sheet 01: mastication treatments and costs

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

Mastication, or mulching, is a mechanical fuel treatment that changes the structure and size of fuels in the stand. This fact sheet describes the kinds of equipment available, where mastication should be used, and treatment factors affecting cost.Other publications in this...

Final Rule to Reduce Toxic Air Emissions from Asphalt Processing and Asphalt Roofing Manufacturing Facilities Fact Sheet

Science.gov (United States)

This page contains a February 2003 fact sheet with information regarding the National Emissions Standards for Hazardous Air Pollutants (NESHAP) for Asphalt Processing and Asphalt Roofing Manufacturing.

Fuels planning: science synthesis and integration; economic uses fact sheet 06: selection criteria analysis

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

Confidence in decisionmaking can often come from knowing if others in similar circumstances would choose the same management strategy. Researchers at the USDA FS Pacific Northwest Research Station and the University of Saskatchewan have developed a Selection Criteria Analysis for answering this very question. This fact sheet discusses factors affecting the choice of...

Catalogue of Energy Efficiency Measures for France: descriptive fact sheets

International Nuclear Information System (INIS)

2012-06-01

ADEME wished to learn about existing effective energy efficiency measures implemented outside of France, whether cross-sectoral or targeted at a specific sector (industry, transport, buildings or agriculture). The objective of this survey was to determine whether any of these measures could be applied in France, with the goal of holding down the growth of energy consumption. This survey has led to the writing of a catalog of 53 two-page fact sheets describing the measures identified as interesting for France. These measures were analysed via classic criteria of evaluation such as cost-efficiency or impact, allowing to highlight the most successful measures for the French territory

Fuels planning: science synthesis and integration; social issues fact sheet 12: Keys to successful collaboration

Science.gov (United States)

Christine Esposito

2006-01-01

Collaborating on fire and fuels management with a host of public and private partners may seem like an impossible undertaking, and presents many challenges. This fact sheet reviews tips for what to focus on as you embark on a collaborative fuels management project.Other...

Women, Work and Health Hazards: A Fact Sheet and Cosmetologists: Health Risks at Work.

Science.gov (United States)

National Commission on Working Women, Washington, DC.

The first part of this document is a fact sheet that provides information on health hazards faced by employed women. It covers the Occupational Safety and Health Act (OSHA), job-related diseases suffered by workers in female-dominated occupations, employer responsibilities under OSHA, and the lack of statistical reporting on job-related disease.…

Fuels planning: science synthesis and integration; economic uses fact sheet 02: log hauling cost

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

Knowing the cost of fuel reduction treatments and associated activities, such as hauling cut trees, is essential for fire and fuels planning. This fact sheet explores the main factors that determine the cost of hauling cut trees and points the user to an interactive tool that can help plan for those and other expenses.

Long-Term Consequences for Teens with Older Sexual Partners. Fact Sheet. Publication #2008-16

Science.gov (United States)

Schelar, Erin; Ryan, Suzanne; Manlove, Jennifer

2008-01-01

Existing research on the risks of having sex at a young age with an older partner has focused on poorer reproductive health outcomes in the adolescent years, but scant attention has been paid to the longer-term implications of these relationships. Using survey data from high school students, this "Fact Sheet" presents findings from recent Child…

Fuels planning: science synthesis and integration; economic uses fact sheet 05: NEPA and economics

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

The National Environmental Policy Act (NEPA) is the law that requires Federal agencies to consider the environmental impacts of their actions, involve the public in the decisionmaking process, and disclose information, starting at the initial stages of planning. This fact sheet discusses when you should consider economics in the NEPA process, when to do an analysis,...

TSCA Chemical Data Reporting Fact Sheet: Chemical Substances which are the Subject of Certain TSCA Actions

Science.gov (United States)

This fact sheet provides guidance for people who may be subject to the Chemical Data Reporting (CDR) rule on how their requirements for reporting for 2016 may be affected when chemical substances are the subject of certain TSCA actions.

Fuels planning: science synthesis and integration; economic uses fact sheet 07: markets and log prices

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

Markets and prices for logs vary widely across the West, fluctuating from place to place in response to regional variables and hauling costs. This fact sheet discusses those variables, locality of log markets, markets for low-value logs, and caveats to consider when using My Fuel Treatment Planner.

Fuels planning: science synthesis and integration; forest structure and fire hazard fact sheet 02: fire hazard

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

Fire hazard reflects the potential fire behavior and magnitude of effects as a function of fuel conditions. This fact sheet discusses crown fuels, surface fuels, and ground fuels and their contribution and involvement in wildland fire.Other publications in this series...

Waste generation and pollution prevention progress fact sheet: Nevada Test Site

International Nuclear Information System (INIS)

1994-01-01

The Nevada Test Site is responsible for maintaining nuclear testing capability, supporting science-based Stockpile Stewardship experiments, maintaining nuclear agency response capability, applying environmental restoration techniques to areas affected by nuclear testing, managing low-level and mixed radioactive waste, investigating demilitarization technologies, investigating counter- proliferation technologies, supporting work-for-others programs and special Department of Defense activities, operating a hazardous materials spill test center, and providing for the commercial development of the site. This fact sheet provides information on routine waste generation and projected reduction by waste type. Also, materials recycled by the Nevada Test Site in 1994 are listed

Fuels planning: science synthesis and integration; social issues fact sheet 16: Prescribed fire and visual quality

Science.gov (United States)

Christine Esposito

2006-01-01

Research shows that, while prescribed burning and other fuels treatments can lower visual quality in some situations, they can also improve it in others. This fact sheet reviews the visual aspects of different levels of prescribed burning.Other publications in this series...

Fact sheet: Ethanol from corn

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-05-31

This fact sheet is intended to provide an overview of the advantages of ethanol from corn, emphasizing ethanol`s contribution to environmental protection and sustainable agriculture. Ethanol, an alternative fuel used as an octane enhancer is produced through the conversion of starch to sugars by enzymes, and fermentation of these sugars to ethanol by yeast. The production process may involve wet milling or dry milling. Both these processes produce valuable by-products, in addition to ethanol and carbon dioxide. Ethanol contains about 32,000 BTU per litre. It is commonly believed that using state-of-the-art corn farming and corn processing processes, the amount of energy contained in ethanol and its by-products would be more than twice the energy required to grow and process corn into ethanol. Ethanol represents the third largest market for Ontario corn, after direct use as animal feed and wet milling for starch, corn sweetener and corn oil. The environmental consequences of using ethanol are very significant. It is estimated that a 10 per cent ethanol blend in gasoline would result in a 25 to 30 per cent decrease in carbon monoxide emissions, a 6 to 10 per cent decrease in net carbon dioxide, a slight increase in nitrous oxide emissions which, however, would still result in an overall decrease in ozone formation, since the significant reduction in carbon monoxide emissions would compensate for any slight increase in nitrous oxide. Volatile organic compounds emission would also decrease by about 7 per cent with a 10 per cent ethanol blend. High level blends could reduce VOCs production by as much as 30 per cent. 7 refs.

Opening the Door to the American Dream: Increasing Higher Education Access and Success for Immigrants. New York Fact Sheet

Science.gov (United States)

Erisman, Wendy; Looney, Shannon

2008-01-01

This fact sheet presents a snapshot of important facts that are specific to the state of New York from the "Opening the Door to the American Dream: Increasing Higher Education Access and Success for Immigrants" report, which exposes systemic barriers that prevent immigrants from entering college and/or completing bachelor's degrees…

Final Rule to Reduce Toxic Air Pollutants from Surface Coating of Plastic Parts and Products Fact Sheet

Science.gov (United States)

This page contains an August 2004 fact sheet with information regarding the final NESHAP for Surface Coating of Plastic Parts and Products. This document provides a summary of the information for the information for this regulation.

77 FR 2743 - Recovery Directorate Fact Sheet 9580.213, Residential Electrical Meter Repair-“Power Up”

Science.gov (United States)

2012-01-19

...] Recovery Directorate Fact Sheet 9580.213, Residential Electrical Meter Repair--``Power Up'' AGENCY: Federal..., Residential Electrical Meter Repair--``Power Up.'' DATES: Comments must be received by February 21, 2012... authority, FEMA may fund the repair of residential electrical meters damaged in a major disaster or...

Better Solar Cells and Manufacturing Processes Using NREL's Ultrafast Quantum Efficiency Method (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2011-08-01

Fact sheet on the FlashQE system, a 2011 R&D 100 Award winner. A solid-state optical system by NREL and Tau Science measures solar cell quantum efficiency in less than a second, enabling a suite of new capabilities for solar cell manufacturers.

Becoming Resilient: Disaster Planning and Recovery: NREL Experts Assist Before and After a Disaster (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

Hotchkiss, E.

2014-08-01

This fact sheet provides information on how private industry; federal, state, and local governments; non-profit organizations; and communities can utilize NREL's expertise, tools, and innovations to incorporate energy efficiency and renewable energy into the planning, recovery, and rebuilding stages of disaster.

Fuels planning: science synthesis and integration; environmental consequences fact sheet 10: The Understory Response Model

Science.gov (United States)

Steve Sutherland; Melanie Miller

2005-01-01

The Understory Response Model is a species-specific computer model that qualitatively predicts change in total species biomass for grasses, forbs, and shrubs after thinning, prescribed fire, or wildfire. The model examines the effect of fuels management on plant survivorship and reproduction. This fact sheet identifies the intended users and uses, required inputs, what...

Fuels planning: science synthesis and integration; environmental consequences fact sheet 05: prescriptions and fire effects

Science.gov (United States)

Melanie Miller

2004-01-01

Fuels planning: science synthesis and integration; environmental consequences fact sheet 5: prescriptions and fire effects. Miller, Melanie. 2004. Res. Note RMRS-RN-23-5-WWW. Fort Collins, CO: U.S. Department of Agriculture, Forest Service, Rocky Mountain Research Station. 2 p. While our understanding of the causes for variation in postfire effects is increasing, burn...

Community Renewable Energy Deployment Provides Replicable Examples of Clean Energy Projects (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2012-09-01

This fact sheet describes the U.S. Department of Energy's Community Renewable Energy Deployment (CommRE) program, which is a more than $20 million effort funded through the American Recovery and Reinvestment Act of 2009, to promote investment in clean energy solutions and provide real-life examples for other local governments, campuses, and small utilities to replicate. Five community-based renewable energy projects received funding from DOE through the CommRE and their progress is detailed.

How Schools Responded to Student Mental Health Needs Following Hurricanes Katrina and Rita. Fact Sheet

Science.gov (United States)

RAND Corporation, 2007

2007-01-01

This fact sheet summarizes a study that examined how schools in the U.S. Gulf Coast region perceived the mental health needs of students after Hurricanes Katrina and Rita and how schools responded. According to the report, despite strong initial efforts to support the mental health needs of students displaced by Hurricanes Katrina and Rita, many…

Fuels planning: science synthesis and integration; economic uses fact sheet 04: My Fuel Treatment Planner

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

In the face of rapidly changing public and political attitudes toward fire and fuel planning, one thing remains constant: the fuel planner is ultimately responsible for making decisions on the land. This fact sheet discusses the options for fuel treatments, and the need, development, and use of the MS Excel-based tool, My Fuel Treatment Planner.

Fuels planning: science synthesis and integration; social issues fact sheet 06: Important considerations for communicating about hazards

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

Effective public education and communication campaigns about wildland fire and fuels management should have clear objectives, and use the right techniques to achieve these objectives. This fact sheet lists seven important considerations for planning or implementing a hazard communication effort.

Fuels planning: science synthesis and integration; economic uses fact sheet 03: economic impacts of fuel treatments

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

With increased interest in reducing hazardous fuels in dry inland forests of the American West, agencies and the public will want to know the economic impacts of fuel reduction treatments. This fact sheet discusses the economic impact tool, a component of My Fuel Treatment Planner, for evaluating economic impacts.

Fuels planning: science synthesis and integration; social issues fact sheet 03: Developing personal responsibility for fuels reduction: More ways to catch and hold people's attention

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

Other fact sheets discuss the different types of information that are useful in explaining to property owners the importance of taking personal responsibility for fuels management on their land. However, for some property owners, new information is not enough-they may need more information in order to understand that change is necessary. This fact sheet discusses ways...

Fuels planning: science synthesis and integration; social issues fact sheet 15: Landscape change and aesthetics

Science.gov (United States)

Christine Esposito

2006-01-01

Fuels management produces changes in the landscape that can impact scenic beauty. If people do not consider a forest to be scenic, they may think that the low scenic quality is a result of poor management or ecological health. This fact sheet looks at the relevency of the effects of natural and human-caused landscape changes, when planning fuels management.

Fuels planning: science synthesis and integration; environmental consequences fact sheet 11: Smoke Impact Spreadsheet (SIS) model

Science.gov (United States)

Trent Wickman; Ann Acheson

2005-01-01

The Smoke Impact Spreadsheet (SIS) is a simple-to-use planning model for calculating particulate matter (PM) emissions and concentrations downwind of wildland fires. This fact sheet identifies the intended users and uses, required inputs, what the model does and does not do, and tells the user how to obtain the model.

Final Air Toxics Standards for Clay Ceramics Manufacturing, Glass Manufacturing, and Secondary Nonferrous Metals Processing Area Sources Fact Sheet

Science.gov (United States)

This page contains a December 2007 fact sheet with information regarding the National Emissions Standards for Hazardous Air Pollutants (NESHAP) for Clay Ceramics Manufacturing, Glass Manufacturing, and Secondary Nonferrous Metals Processing Area Sources

Fuels planning: science synthesis and integration; environmental consequences fact sheet 01: Fire Effects Information System (FEIS)

Science.gov (United States)

Steve Sutherland

2004-01-01

The Fire Effects Information System (FEIS) provides accessible, up-to-date fire effects summaries, taken from current English-language literature, for almost 900 plant species, about 100 animal species, and 16 Kuchler plant communities found on the North American continent. This fact sheet discusses the development of FEIS and what is contained in the species summary....

Fuels planning: science synthesis and integration; social issues fact sheet 14: Landscape preference in forested ecosystems

Science.gov (United States)

Christine Esposito

2006-01-01

It is important to understand what types of landscape settings most people prefer to be able to plan fuels treatment and other forest management activities that will be acceptable to the general public. This fact sheet considers the four common elements of visually preferred forest settings: large trees; herbacious, smooth groundcover; open midstory canopy; and vistas...

State and Local Clean Energy Policy Primer: Getting from Here to Clean Electricity with Policy (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2011-04-01

This fact sheet proposes a framework for how states and localities can build policy portfolios by first setting the stage for clean energy in the market with low cost policies, and then growing the market with successive policies until the need for financial incentives can be reduced and eventually eliminated.

Training Sessions and Materials Present Ways to Improve System Efficiency: OIT Technical Assistance Fact Sheet: Training

International Nuclear Information System (INIS)

Ericksen, E.

1999-01-01

Interested in learning about innovative ways to improve the efficiency of your plant's steam, electric motor, and compressed air systems? This US Department of Energy Office of Industrial Technologies fact sheet offers information regarding training sessions, teleconferences, and various training materials to teach you and your company ways to reduce energy use, save money, and reduce waste and pollution through system optimization

Fuels planning: science synthesis and integration; social issues fact sheet 05: The importance of working locally

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

People who evaluate their actions in terms of what others think are often said to be guided by community norms. With respect to fuels management, this means that when you are "selling" a property owner on taking steps to reduce fuels, you are not just "selling" to one person, but to a network of people. This fact sheet discusses three tools to help...

Oil Notifications: Emergency Response Notification System (ERNS) fact sheet

International Nuclear Information System (INIS)

1992-04-01

The Emergency Response Notification System (ERNS) is a national computer database which provides the only centralized mechanism for documenting and verifying incident notification information as initially reported to the National Response Center (NRC), the U.S. Environmental Protection Agency (EPA), and to a limited extent, the U.S. Coast Guard (USCG). The initial notification data may be followed up with updated information from various Federal, State and local response authorities, as appropriate. ERNS contains data that can be used to analyze release notifications, support emergency planning efforts, and assist decision makers in developing spill prevention programs. The fact sheet provides summary information on notifications of releases of oil reported in accordance with the Clean Water Act (CWA). Under Section 311 of the CWA, discharges of oil which: (1) cause a sheen to appear on the surface of the water; (2) violate applicable water quality standards; or (3) cause sludge or emulsion to be deposited beneath the surface of the water or adjoining shoreline, must be reported to the NRC

Fuels planning: science synthesis and integration; environmental consequences fact sheet 08: Evaluating sedimentation risks associated with fuel management

Science.gov (United States)

William Elliot; Pete Robichaud

2005-01-01

This fact sheet describes the sources of sediment in upland forest watersheds in the context of fuel management activities. It presents the dominant forest soil erosion processes, and the principles behind the new sediment delivery interface developed to aid in erosion analysis of fuel management projects.

9/11 and the War on Terror in Curricula and in State Standards Documents. CIRCLE Fact Sheet

Science.gov (United States)

Stoddard, Jeremy; Hess, Diana

2011-01-01

This Fact Sheet reports findings from an ongoing study of the representation of 9/11 and terrorism in curricula, textbooks, and state standards documents. The study was conducted in three stages. The first two stages focused on how supplemental curricula and best-selling social studies textbooks published between 2002-2010 present the events of…

Fuels planning: science synthesis and integration; social issues fact sheet 18: Issues affecting social acceptability of fuels treatments

Science.gov (United States)

Christine Esposito

2006-01-01

Researchers have tried to understand how information about forest management can influence a person's landscape preferences and aesthetic appreciation. These findings are relevant for fuels management projects, since these projects are often characterized by conflicts between aesthetic and ecological objectives. This fact sheet discusses different aspects and ways...

Fuels planning: science synthesis and integration; social issues fact sheet 17: Considering social acceptability of fuels treatments

Science.gov (United States)

Christine Esposito

2006-01-01

When making decisions about fuels treatments, forest managers need to assess not only the biological impacts of a treatment, but the social impacts as well. Social acceptability is based on value judgments by people-their notions of what is "good" and what is "better." This fact sheet discusses six questions that may be useful for framing initial...

Using the Global Burden of Disease study to assist development of nation-specific fact sheets to promote prevention and control of hypertension and reduction in dietary salt: a resource from the World Hypertension League.

Science.gov (United States)

Campbell, Norm R C; Lackland, Daniel T; Lisheng, Liu; Niebylski, Mark L; Nilsson, Peter M; Zhang, Xin-Hua

2015-03-01

Increased blood pressure and high dietary salt are leading risks for death and disability globally. Reducing the burden of both health risks are United Nations' targets for reducing noncommunicable disease. Nongovernmental organizations and individuals can assist by ensuring widespread dissemination of the best available facts and recommended interventions for both health risks. Simple but impactful fact sheets can be useful for informing the public, healthcare professionals, and policy makers. The World Hypertension League has developed fact sheets on dietary salt and hypertension but in many circumstances the greatest impact would be obtained from national-level fact sheets. This manuscript provides instructions and a template for developing fact sheets based on the Global Burden of Disease study and national survey data. ©2015 Wiley Periodicals, Inc.

The acquisition of dangerous biological materials: Technical facts sheets to assist risk assessments of 46 potential BW agents

Energy Technology Data Exchange (ETDEWEB)

Aceto, Donato Gonzalo [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Astuto-Gribble, Lisa M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gaudioso, Jennifer M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2007-11-01

Numerous terrorist organizations have openly expressed interest in producing and deploying biological weapons. However, a limiting factor for many terrorists has been the acquisition of dangerous biological agents, as evidenced by the very few successful instances of biological weapons use compared to the number of documented hoaxes. Biological agents vary greatly in their ability to cause loss of life and economic damage. Some agents, if released properly, can kill many people and cause an extensive number of secondary infections; other agents will sicken only a small number of people for a short period of time. Consequently, several biological agents can potentially be used to perpetrate a bioterrorism attack but few are likely capable of causing a high consequence event. It is crucial, from a US national security perspective, to more deeply understand the likelihood that terrorist organizations can acquire the range of these agents. Few studies have attempted to comprehensively compile the technical information directly relevant to the acquisition of dangerous bacteria, viruses and toxins. In this report, technical fact sheets were assembled for 46 potentially dangerous biological agents. Much of the information was taken from various research sources which could ultimately and significantly expedite and improve bioterrorism threat assessments. By systematically examining a number of specific agent characteristics included in these fact sheets, it may be possible to detect, target, and implement measures to thwart future terrorist acquisition attempts. In addition, the information in these fact sheets may be used as a tool to help laboratories gain a rudimentary understanding of how attractive a method laboratory theft is relative to other potential acquisition modes.

Fuels planning: science synthesis and integration; social issues fact sheet 13: Strategies for managing fuels and visual quality

Science.gov (United States)

Christine Esposito

2006-01-01

The public's acceptance of forest management practices, including fuels reduction, is heavily based on how forests look. Fuels managers can improve their chances of success by considering aesthetics when making management decisions. This fact sheet reviews a three-part general strategy for managing fuels and visual quality: planning, implementation, and monitoring...

7 CFR Exhibit D to Subpart B of... - Fact Sheet-The Federal Interagency Task Force on Food and Shelter for the Homeless

Science.gov (United States)

2010-01-01

... (CONTINUED) PROPERTY MANAGEMENT Management of Property Exhibit D to Subpart B of Part 1955—Fact Sheet—The... 7 Agriculture 14 2010-01-01 2009-01-01 true Fact Sheet-The Federal Interagency Task Force on Food and Shelter for the Homeless D Exhibit D to Subpart B of Part 1955 Agriculture Regulations of the...

Fuels planning: science synthesis and integration; environmental consequences fact sheet 13: Root Disease Analyzer-Armillaria Response Tool (ART)

Science.gov (United States)

Geral I. McDonald; Philip D. Tanimoto; Thomas M. Rice; David E. Hall; Jane E. Stewart; Paul J. Zambino; Jonalea R. Tonn; Ned B. Klopfenstein; Mee-Sook Kim

2005-01-01

The Root Disease Analyzer-Armillaria Response Tool (ART) is a Web-based tool that estimates Armillaria root disease risk in dry forests of the Western United States. This fact sheet identifies the intended users and uses, required inputs, what the model does and does not do, and tells the user how to obtain the model.

Fuels planning: science synthesis and integration; social issues fact sheet 04: Three critical topics to cover when talking about hazards

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

The amount of science applicable to the management of wildfire hazards is increasing daily. In addition, the attitudes of landowners and policymakers about fire and fuels management are changing. This fact sheet discusses three critical keys to communicating about wildfire hazards.

Fuels planning: science synthesis and integration; environmental consequences fact sheet 03: structure fires in the wildland-urban interface

Science.gov (United States)

Steve Sutherland

2004-01-01

National Fire Protection Association (NFPA) data indicate that wildfires destroyed approximately 9,000 homes between 1985 and 1994 in the United States. The loss of homes to wildfire has had a significant impact on Federal fire policy. This fact sheet discusses the causes of home ignitions in the wildland-urban interface, home ignition zones, how to reduce home...

Fuels planning: science synthesis and integration; social issues fact sheet 07: The "laws" of effective public education about fire hazards

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

Within the past 10 years, breakthrough research has identified factors that are most important for effectively communicating about wildland fire hazards. This fact sheet discusses seven "Laws" of effective public communication that should be considered in any state-of-the-art education campaign.

Sewage Sludge Incinerators: Final Standards of Performance for New Stationary Sources and Emission Guidelines for Existing Sources Final Rule Fact Sheets

Science.gov (United States)

This page contains a February 2011 fact sheet with information regarding the final NSPS and Emission Guidelines for Existing Sources for Sewage Sludge Incinerators (SSI). This document provides a summary of the information for these regulations.

Genetic Interactions of STAT3 and Anticancer Drug Development

International Nuclear Information System (INIS)

Fang, Bingliang

2014-01-01

Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors

Fuels planning: science synthesis and integration; forest structure and fire hazard fact sheet 03: visualizing forest structure and fuels

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

The software described in this fact sheet provides managers with tools for visualizing forest and fuels information. Computer-based landscape simulations can help visualize stand and landscape conditions and the effects of different management treatments and fuel changes over time. These visualizations can assist forest planning by considering a range of management...

Other Solid Waste Incineration (OSWI) Units Standards of Performance for New Stationary Sources and Emission Guidelines for Existing Sources Fact Sheets

Science.gov (United States)

This page contains a November 2005, and and November 2006 fact sheet with information regarding the final and proposed NSPS and Emission Guidelines for Existing Sources for OSWI. This document provides a summary of the information for this regulation

Fuels planning: science synthesis and integration; forest structure and fire hazard fact sheet 04: role of silviculture in fuel treatments

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

The principal goals of fuel treatments are to reduce fireline intensities, reduce the potential for crown fires, improve opportunities for successful fire suppression, and improve forest resilience to forest fires. This fact sheet discusses thinning, and surface fuel treatments, as well as challenges associated with those treatments.

New technology for sulfide reductions and increased oil recovery: Petroleum project fact sheet

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-12-14

This Fact Sheet is written for the Inventions and Innovations Program about a new technology for sulfide reduction and increased oil recovery. The new technology, called Bio-Competitive Exclusion (BCX), results in greater oil production and prevents the production of corrosive hydrogen sulfide in oil and gas reservoirs. This BCX process is initiated and maintained by a new product, called Max-Well 2000, in which nutrients are custom designed to stimulate targeted beneficial microorganisms that live in every oil and gas reservoir. Rapid growth of these microorganisms excludes activity of harmful sulfide-producing bacteria and produces by-products that serve as effective tertiary oil recovery agents and as sulfide degradation agents. Oil and gas production is both increased and sweetened.

Rising Above the Water: New Orleans Implements Energy Efficiency and Sustainability Practices Following Hurricanes Katrina and Rita (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2012-07-01

This fact sheet describes the technical assistance that the U.S. Department of Energy, through its National Renewable Energy Laboratory, provided to New Orleans, Louisiana, which helped the city incorporate energy efficiency into its rebuilding efforts for K-12 schools and homes following Hurricanes Katrina and Rita. NREL also provided support and analysis on energy policy efforts.

High Blood Pressure Facts

Science.gov (United States)

... Stroke Heart Disease Cholesterol Salt Million Hearts® WISEWOMAN High Blood Pressure Facts Recommend on Facebook Tweet Share Compartir On ... Top of Page CDC Fact Sheets Related to High Blood Pressure High Blood Pressure Pulmonary Hypertension Heart Disease Signs ...

Small Businesses Save Big: A Borrower's Guide To Increase the Bottom Line Using Energy Efficiency (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2015-01-01

Dollars saved through energy efficiency can directly impact your bottom line. Whether you are planning for a major renovation or upgrading individual pieces of building equipment, these improvements can help reduce operating costs, save on utility bills, and boost profits. This fact sheet provides a guide for small businesses to find the resources to increase the energy efficiency of their buildings.

Technologies for Distributed Energy Resources. Federal Energy Management Program (FEMP) Technical Assistance Fact Sheet

International Nuclear Information System (INIS)

Pitchford, P.; Brown, T.

2001-01-01

This four-page fact sheet describes distributed energy resources for Federal facilities, which are being supported by the U.S. Department of Energy's (DOE's) Federal Energy Management Program (FEMP). Distributed energy resources include both existing and emerging energy technologies: advanced industrial turbines and microturbines; combined heat and power (CHP) systems; fuel cells; geothermal systems; natural gas reciprocating engines; photovoltaics and other solar systems; wind turbines; small, modular biopower; energy storage systems; and hybrid systems. DOE FEMP is investigating ways to use these alternative energy systems in government facilities to meet greater demand, to increase the reliability of the power-generation system, and to reduce the greenhouse gases associated with burning fossil fuels

Fuels planning: science synthesis and integration; forest structure and fire hazard fact sheet 01: forest structure and fire hazard overview

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

Many managers and policymakers guided by the National Environmental Policy Act process want to understand the scientific principles on which they can base fuel treatments for reducing the size and severity of wildfires. These Forest Structure and Fire Hazard fact sheets discuss how to estimate fire hazard, how to visualize fuel treatments, and how the role of...

Facts for Families from the American Academy of Child and Adolescent Psychiatry [1991].

Science.gov (United States)

American Academy of Child and Adolescent Psychiatry, Washington, DC.

Nine fact sheets relevant to children's emotional well-being are presented in this document. The first fact sheet, "Teenagers with Eating Disorders" focuses on anorexia nervosa and bulimia. The second fact sheet, "Children and Grief" describes age-related responses to death, and ways of coping with a death in a family that…

Facts for Families from the American Academy of Child and Adolescent Psychiatry [1989].

Science.gov (United States)

American Academy of Child and Adolescent Psychiatry, Washington, DC.

Six fact sheets on issues relevant to children's emotional well being are presented in this document. The first fact sheet, "Children and Divorce" provides information for parents to consider when getting a divorce. Parents are encouraged to be aware of the stress that the events surrounding a divorce cause for the child. The second fact sheet,…

Small Businesses Save Big: A Guide to Help SBA Lenders Understand and Communicate the Value of Energy Efficiency Investments (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2015-01-01

Dollars saved through energy efficiency can directly impact your bottom line. Whether you are planning for a major renovation or upgrading individual pieces of building equipment, these improvements can help reduce operating costs, save on utility bills, and boost profits. This fact sheet provides guidelines for SBA lenders to understand the value of financing energy efficiency investments.

Fuels planning: science synthesis and integration; environmental consequences fact sheet 12: Water Erosion Prediction Project (WEPP) Fuel Management (FuMe) tool

Science.gov (United States)

William Elliot; David Hall

2005-01-01

The Water Erosion Prediction Project (WEPP) Fuel Management (FuMe) tool was developed to estimate sediment generated by fuel management activities. WEPP FuMe estimates sediment generated for 12 fuel-related conditions from a single input. This fact sheet identifies the intended users and uses, required inputs, what the model does, and tells the user how to obtain the...

Eriocalyxin B Inhibits STAT3 Signaling by Covalently Targeting STAT3 and Blocking Phosphorylation and Activation of STAT3.

Directory of Open Access Journals (Sweden)

Xiaokui Yu

Full Text Available Activated STAT3 plays an important role in oncogenesis by stimulating cell proliferation and resisting apoptosis. STAT3 therefore is an attractive target for cancer therapy. We have screened a traditional Chinese herb medicine compound library and found Eriocalyxin B (EB, a diterpenoid from Isodon eriocalyx, as a specific inhibitor of STAT3. EB selectively inhibited constitutive as well as IL-6-induced phosphorylation of STAT3 and induced apoptosis of STAT3-dependent tumor cells. EB did not affect the upstream protein tyrosine kinases or the phosphatase (PTPase of STAT3, but rather interacted directly with STAT3. The effects of EB could be abolished by DTT or GSH, suggesting a thiol-mediated covalent linkage between EB and STAT3. Site mutagenesis of cysteine in and near the SH2 domain of STAT3 identified Cys712 to be the critical amino acid for the EB-induced inactivation of STAT3. Furthermore, LC/MS/MS analyses demonstrated that an α, β-unsaturated carbonyl of EB covalently interacted with the Cys712 of STAT3. Computational modeling analyses also supported a direct interaction between EB and the Cys712 of STAT3. These data strongly suggest that EB directly targets STAT3 through a covalent linkage to inhibit the phosphorylation and activation of STAT3 and induces apoptosis of STAT3-dependent tumor cells.

Case Management for Individuals with Mental Retardation. ARC Facts.

Science.gov (United States)

Association for Retarded Citizens, Arlington, TX.

A question-and-answer format is used in this fact sheet to provide information on case management for individuals with mental retardation. The fact sheet describes the major components of a case management system, the role of the case manager, the individual's or family's role in case management, providers of case management services and systems…

Clinical Social Work. State Laws Governing Independent Practice and Reimbursement of Services. Fact Sheet for the Honorable Daniel K. Inouye, United States Senate.

Science.gov (United States)

General Accounting Office, Washington, DC. Div. of Human Resources.

This fact sheet on state laws governing the independent practice and reimbursement of services for clinical social workers contains information from questionnaires sent to the state agencies responsible for health insurance regulations and Medicaid and licensing activities. Information on Ohio, the only state which did not respond, is not…

Photovoltaics (PV) as an Eligible Measure in Residential PACE Programs: Benefits and Challenges (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

Coughlin, J.

2010-06-01

Property Assessed Clean Energy (PACE) financing is one of several new financial models broadening access to clean energy by addressing the barrier of initial capital cost. The majority of the PACE programs in the market today include PV as an eligible measure. PV appeals to homeowners as a way to reduce utility bills, self-generate sustainable power, increase energy independence and demonstrate a commitment to the environment. If substantial state incentives for PV exist, PV projects can be economic under PACE, especially when partnered with good net metering policies. At the same time, PV is expensive relative to other eligible measures with a return on investment horizon that might exceed program targets. This fact sheet reviews the benefits and potential challenges of including PV in PACE programs.

Physical Therapy and Occupational Therapy: Suggested Readings [and] Physical Therapy: Supply/Demand--Some Facts [and] Occupational Therapy: Supply and Demand--Some Facts. Information on Personnel Supply and Demand.

Science.gov (United States)

National Clearinghouse for Professions in Special Education, Reston, VA.

Brought together are two fact sheets on the supply of and demand for physical therapists and occupational therapists. The fact sheets cite statistical data from the National Easter Seal Society, the American Physical Therapy Association, and the American Occupational Therapy Association. The cited facts focus on the need to recruit and retain…

Fuels planning: science synthesis and integration; social issues fact sheet 02: Developing personal responsibility for fuels reduction: Types of information to encourage proactive behavior

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

Fuels management responsibilities may include providing local property owners with the information for taking responsibility for reducing fuels on their land. This fact sheet discusses three different types of information that may be useful in programs to engage property owners in fuel reduction activities.

Fuels planning: science synthesis and integration; environmental consequences fact sheet 09: Fire and Fuels Extension to the Forest Vegetation Simulator (FFE-FVS)

Science.gov (United States)

Elizabeth Reinhardt

2005-01-01

FFE-FVS is a model linking stand development, fuel dynamics, fire behavior and fire effects. It allows comparison of mid- to long-term effects of management alternatives including harvest, mechanical fuel treatment, prescribed fire, salvage, and no action. This fact sheet identifies the intended users and uses, required inputs, what the model does, and tells the user...

NREL Showcases Hydrogen Internal Combustion Engine Bus, Helps DOE Set Standards for Outreach (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2010-11-01

This fact sheet describes the National Renewable Energy Laboratory's (NREL's) accomplishments in showcasing a Ford hydrogen-powered internal combustion engine (H2ICE) bus at The Taste of Colorado festival in Denver. NREL started using its U.S. Department of Energy-funded H2ICE bus in May 2010 as the primary shuttle vehicle for VIP visitors, members of the media, and new employees. In September 2010, NREL featured the bus at The Taste of Colorado. This was the first major outreach event for the bus. NREL's educational brochure, vehicle wrap designs, and outreach efforts serve as a model for other organizations with DOE-funded H2ICE buses. Work was performed by the Hydrogen Education Group and Market Transformation Group in the Hydrogen Technologies and Systems Center.

Fuels planning: science synthesis and integration; social issues fact sheet 01: Developing personal responsibility for fuels reduction: Building a successful program to engage property owners

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2004-01-01

In the course of work as a land manager, you will no doubt be involved in developing programs to achieve various objectives, including the improvement of fuels management on private lands. This fact sheet describes six steps that will help you plan and conduct a successful program.

Sandia National Laboratories: News: Publications: Fact Sheets

Science.gov (United States)

Environmental Management System Pollution Prevention History 60 impacts Diversity Locations Facts & Figures Does Sandia Buy? Opportunities Small Business Procurement Technical Assistance Program (PTAP) Current Technology Partnerships Business, Industry, & Non-Profits Government Universities Center for

Back Pain Facts and Statistics

Science.gov (United States)

... Marketing Patient Fact Sheets Contact the ACA State Licensing Boards Research JMPT Abstracts Latest Issue Evidence in ... Chiropractic Posture Backpack Safety Spinal Health Winter Activities Kids and Sports Exercising Outdoors with Baby Gardening Chronic ...

Facts about food irradiation: Controlling the process

International Nuclear Information System (INIS)

1991-01-01

This fact sheet briefly reviews the procedures that exist to control the process of food irradiation. It also summarizes the difficulties in identifying irradiated food, which stem from the fact that irradiation does not physically change the food or cause significant chemical changes in foods. 4 refs

Identification of STAT1 and STAT3 specific inhibitors using comparative virtual screening and docking validation.

Directory of Open Access Journals (Sweden)

Malgorzata Szelag

Full Text Available Signal transducers and activators of transcription (STATs facilitate action of cytokines, growth factors and pathogens. STAT activation is mediated by a highly conserved SH2 domain, which interacts with phosphotyrosine motifs for specific STAT-receptor contacts and STAT dimerization. The active dimers induce gene transcription in the nucleus by binding to a specific DNA-response element in the promoter of target genes. Abnormal activation of STAT signaling pathways is implicated in many human diseases, like cancer, inflammation and auto-immunity. Searches for STAT-targeting compounds, exploring the phosphotyrosine (pTyr-SH2 interaction site, yielded many small molecules for STAT3 but sparsely for other STATs. However, many of these inhibitors seem not STAT3-specific, thereby questioning the present modeling and selection strategies of SH2 domain-based STAT inhibitors. We generated new 3D structure models for all human (hSTATs and developed a comparative in silico docking strategy to obtain further insight into STAT-SH2 cross-binding specificity of a selection of previously identified STAT3 inhibitors. Indeed, by primarily targeting the highly conserved pTyr-SH2 binding pocket the majority of these compounds exhibited similar binding affinity and tendency scores for all STATs. By comparative screening of a natural product library we provided initial proof for the possibility to identify STAT1 as well as STAT3-specific inhibitors, introducing the 'STAT-comparative binding affinity value' and 'ligand binding pose variation' as selection criteria. In silico screening of a multi-million clean leads (CL compound library for binding of all STATs, likewise identified potential specific inhibitors for STAT1 and STAT3 after docking validation. Based on comparative virtual screening and docking validation, we developed a novel STAT inhibitor screening tool that allows identification of specific STAT1 and STAT3 inhibitory compounds. This could increase our

Alfabetizacion de las personas que son sordas e invidentes. Hoja informativa de DB-LINK (Literacy for Persons Who Are Deaf-Blind. DB-LINK Fact Sheet).

Science.gov (United States)

Miles, Barbara

This fact sheet discusses the importance of literacy for individuals who are deaf-blind, the social functions of reading and writing, and conditions necessary for the development of literacy. Strategies for promoting literacy among this population are described and include: (1) invite children and adults who are deaf-blind to observe as you use…

Know How to Use Your Asthma Inhaler

Medline Plus

Full Text Available ... the Nation Fact Sheet State Data Profiles (2011) Work-related Asthma NCHS Asthma FastStats Survey Questions Resources for Health Professionals and Schools Healthcare Professionals Public Health Professionals ...

CERN Quick Facts 2017 (French version)

CERN Multimedia

Mobs, Esma

2017-01-01

Facts about CERN, the contributions of its Member States, its machines and experiments, the number of its employees and users, management structure, etc. Previously called "CERN General Information Sheet"

CERN Quick Facts 2016 (French version)

CERN Multimedia

AUTHOR|(CDS)2070305

2016-01-01

Facts about CERN, the contributions of its Member States, its machines and experiments, the number of its employees and users, management structure, etc. Previously called "CERN General Information Sheet"

CERN Quick Facts 2016 (English version)

CERN Multimedia

AUTHOR|(CDS)2070305

2016-01-01

Facts about CERN, the contributions of its Member States, its machines and experiments, the number of its employees and users, management structure, etc. Previously called "CERN General Information Sheet"

CERN Quick Facts 2017 (English version)

CERN Multimedia

Mobs, Esma

2017-01-01

Facts about CERN, the contributions of its Member States, its machines and experiments, the number of its employees and users, management structure, etc. Previously called "CERN General Information Sheet"

Emotional Disturbance. NICHCY Disability Fact Sheet #5

Science.gov (United States)

National Dissemination Center for Children with Disabilities, 2010

2010-01-01

The mental health of our children is a natural and important concern for us all. The fact is, many mental disorders have their beginnings in childhood or adolescence, yet may go undiagnosed and untreated for years. "Umbrella" terms such as emotional disturbance, behavioral disorders, or mental illness are used to refer to mental…

Facts about Volunteers. NCJW Center for the Child Fact Sheet Number 5.

Science.gov (United States)

National Council of Jewish Women, New York, NY. Center for the Child.

Volunteering is a vital and widespread activity in the United States; in fact, volunteers perform many essential community functions. Those who believe that most volunteers are women with time on their hands, that volunteers just do "charity work," and that volunteers are a source of cheap labor who can replace paid professionals and…

In silico simulations of STAT1 and STAT3 inhibitors predict SH2 domain cross-binding specificity.

Science.gov (United States)

Szelag, Malgorzata; Sikorski, Krzysztof; Czerwoniec, Anna; Szatkowska, Katarzyna; Wesoly, Joanna; Bluyssen, Hans A R

2013-11-15

Signal transducers and activators of transcription (STATs) comprise a family of transcription factors that are structurally related and which participate in signaling pathways activated by cytokines, growth factors and pathogens. Activation of STAT proteins is mediated by the highly conserved Src homology 2 (SH2) domain, which interacts with phosphotyrosine motifs for specific contacts between STATs and receptors and for STAT dimerization. By generating new models for human (h)STAT1, hSTAT2 and hSTAT3 we applied comparative in silico docking to determine SH2-binding specificity of the STAT3 inhibitor stattic, and of fludarabine (STAT1 inhibitor). Thus, we provide evidence that by primarily targeting the highly conserved phosphotyrosine (pY+0) SH2 binding pocket stattic is not a specific hSTAT3 inhibitor, but is equally effective towards hSTAT1 and hSTAT2. This was confirmed in Human Micro-vascular Endothelial Cells (HMECs) in vitro, in which stattic inhibited interferon-α-induced phosphorylation of all three STATs. Likewise, fludarabine inhibits both hSTAT1 and hSTAT3 phosphorylation, but not hSTAT2, by competing with the highly conserved pY+0 and pY-X binding sites, which are less well-preserved in hSTAT2. Moreover we observed that in HMECs in vitro fludarabine inhibits cytokine and lipopolysaccharide-induced phosphorylation of hSTAT1 and hSTAT3 but does not affect hSTAT2. Finally, multiple sequence alignment of STAT-SH2 domain sequences confirmed high conservation between hSTAT1 and hSTAT3, but not hSTAT2, with respect to stattic and fludarabine binding sites. Together our data offer a molecular basis that explains STAT cross-binding specificity of stattic and fludarabine, thereby questioning the present selection strategies of SH2 domain-based competitive small inhibitors. © 2013 Elsevier B.V. All rights reserved.

Know How to Use Your Asthma Inhaler

Medline Plus

Full Text Available ... Impact on the Nation Fact Sheet State Data Profiles (2011) Work-related Asthma NCHS Asthma FastStats Survey Questions Resources for Health Professionals and Schools Healthcare Professionals Public Health Professionals School ...

A STAT3-decoy oligonucleotide induces cell death in a human colorectal carcinoma cell line by blocking nuclear transfer of STAT3 and STAT3-bound NF-κB

Directory of Open Access Journals (Sweden)

Le Coquil Stéphanie

2011-04-01

Full Text Available Abstract Background The transcription factor STAT3 (signal transducer and activator of transcription 3 is frequently activated in tumor cells. Activated STAT3 forms homodimers, or heterodimers with other TFs such as NF-κB, which becomes activated. Cytoplasmic STAT3 dimers are activated by tyrosine phosphorylation; they interact with importins via a nuclear localization signal (NLS one of which is located within the DNA-binding domain formed by the dimer. In the nucleus, STAT3 regulates target gene expression by binding a consensus sequence within the promoter. STAT3-specific decoy oligonucleotides (STAT3-decoy ODN that contain this consensus sequence inhibit the transcriptional activity of STAT3, leading to cell death; however, their mechanism of action is unclear. Results The mechanism of action of a STAT3-decoy ODN was analyzed in the colon carcinoma cell line SW 480. These cells' dependence on activated STAT3 was verified by showing that cell death is induced by STAT3-specific siRNAs or Stattic. STAT3-decoy ODN was shown to bind activated STAT3 within the cytoplasm, and to prevent its translocation to the nucleus, as well as that of STAT3-associated NF-κB, but it did not prevent the nuclear transfer of STAT3 with mutations in its DNA-binding domain. The complex formed by STAT3 and the STAT3-decoy ODN did not associate with importin, while STAT3 alone was found to co-immunoprecipitate with importin. Leptomycin B and vanadate both trap STAT3 in the nucleus. They were found here to oppose the cytoplasmic trapping of STAT3 by the STAT3-decoy ODN. Control decoys consisting of either a mutated STAT3-decoy ODN or a NF-κB-specific decoy ODN had no effect on STAT3 nuclear translocation. Finally, blockage of STAT3 nuclear transfer correlated with the induction of SW 480 cell death. Conclusions The inhibition of STAT3 by a STAT3-decoy ODN, leading to cell death, involves the entrapment of activated STAT3 dimers in the cytoplasm. A mechanism is

Monoclonal Antibodies Specific for STAT3β Reveal Its Contribution to Constitutive STAT3 Phosphorylation in Breast Cancer

Directory of Open Access Journals (Sweden)

Uddalak Bharadwaj

2014-09-01

Full Text Available Since its discovery in mice and humans 19 years ago, the contribution of alternatively spliced Stat3, Stat3β, to the overall functions of Stat3 has been controversial. Tyrosine-phosphorylated (p Stat3β homodimers are more stable, bind DNA more avidly, are less susceptible to dephosphorylation, and exhibit distinct intracellular dynamics, most notably markedly prolonged nuclear retention, compared to pStat3α homodimers. Overexpression of one or the other isoform in cell lines demonstrated that Stat3β acted as a dominant-negative of Stat3α in transformation assays; however, studies with mouse strains deficient in one or the other isoform indicated distinct contributions of Stat3 isoforms to inflammation. Current immunological reagents cannot differentiate Stat3β proteins derived from alternative splicing vs. proteolytic cleavage of Stat3α. We developed monoclonal antibodies that recognize the 7 C-terminal amino acids unique to Stat3β (CT7 and do not cross-react with Stat3α. Immunoblotting studies revealed that levels of Stat3β protein, but not Stat3α, in breast cancer cell lines positively correlated with overall pStat3 levels, suggesting that Stat3β may contribute to constitutive Stat3 activation in this tumor system. The ability to unambiguously discriminate splice alternative Stat3β from proteolytic Stat3β and Stat3α will provide new insights into the contribution of Stat3β vs. Stat3α to oncogenesis, as well as other biological and pathological processes.

Legislation and regulations for prevention of legionella in drinking and hot water. Explanation of care obligation, alternate techniques and risk assessment. Fact sheet; Wet- en regelgeving Legionellapreventie in drink- en warmtapwater. Uitleg over zorgplicht, alternatieve technieken en risico-analyse. Informatieblad

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-03-15

The reason for this fact sheet is the revision of the drinking water regulations, including the regulations for the prevention of legionella, July 1, 2011. Many market parties consider the regulations as complex, even after the revision. This fact sheet provides more clarity [Dutch] Aanleiding voor dit informatieblad is de op 1 juli 2011 herziene drinkwaterregelgeving, inclusief de voor legionellapreventie relevante bepalingen. Veel marktpartijen ervaren deze regelgeving, ook na herziening, als complex. Dit informatieblad verschaft meer duidelijkheid.

HCUP Fast Stats

Data.gov (United States)

U.S. Department of Health & Human Services — HCUP Fast Stats provides easy access to the latest HCUP-based statistics for health information topics. HCUP Fast Stats uses visual statistical displays in...

Gun Sales. Firearm Facts.

Science.gov (United States)

Duker, Laurie, Ed.

Minimal federal regulations on firearm sales have facilitated the proliferation of guns, gun owners, and gun dealers in the United States. This fact sheet offers data on the growing number of firearm dealers, the relative ease of obtaining and keeping a license to sell guns from the Federal Bureau of Alcohol, Tobacco, and Firearms, the lack of…

STAT5A and STAT5B have opposite correlations with drug response gene expression

International Nuclear Information System (INIS)

Lamba, V.; Jia, B.; Liang, F.

2016-01-01

Introduction: STAT5A and STAT5B are important transcription factors that play a key role in regulation of several important physiological processes including proliferation, survival, mediation of responses to cytokines and in regulating gender differences in drug response genes such as the hepatic cytochrome P450s (CYPs) that are responsible for a large majority of drug metabolism reactions in the human body. STAT5A and STAT5b have a high degree of sequence homology and have been reported to have largely similar functions. Recent studies have, however, indicated that they can also often have distinct and unique roles in regulating gene expression. Objective: In this study, we evaluated the association of STAT5A and STAT5B mRNA expression levels with those of several key hepatic cytochrome P450s (CYPs) and hepatic transcription factors (TFs) and evaluated the potential roles of STAT5A and 5b in mediating gender differences in these CYPs and TFs. Methods: Expression profiling for major hepatic CYP isoforms and transcription factors was performed using RNA sequencing (RNA-seq) in 102 human liver samples (57 female, 45 male). Real time PCR gene expression data for selected CYPs and TFs was available on a subset of 50 human liver samples (25 female, 25 male) and was used to validate the RNA-seq findings. Results: While STAT5A demonstrated significant negative correlation with expression levels of multiple hepatic transcription factors (including NR1I2 and HNF4A) and DMEs such as CYP3A4 and CYP2C19, STAT5B expression was observed to demonstrate positive associations with several CYPs and TFs analyzed. As STAT5A and STAT5B have been shown to be important in regulation of gender differences in CYPs, we also analyzed STAT5A and 5b associations with CYPs and TFs separately in males and females and observed gender dependent differential associations of STATs with several CYPs and TFs. Results from the real time PCR validation largely supported our RNA-seq findings

Fact sheets relating to use of geothermal energy in the United States

Energy Technology Data Exchange (ETDEWEB)

None

1980-12-01

A compilation of data relating to geothermal energy in each of the 50 states is presented. The data are summarized on one page for each state. All summary data sheets use a common format. Following the summary data sheet there are additional data on the geology of each state pertaining to possible hydrothermal/geothermal resources. Also there is a list of some of the reports available pertaining to the state and state energy contacts. The intent of these documents is to present in a concise form reference data for planning by the Department of Energy.

Brain Drain: A Child's Brain on Poverty. Poverty Fact Sheet

Science.gov (United States)

Damron, Neil

2015-01-01

"Brain Drain: A Child's Brain on Poverty," released in March 2015 and prepared by intern Neil Damron, explores the brain's basic anatomy and recent research findings suggesting that poverty affects the brain development of infants and young children and the potential lifelong effects of the changes. The sheet draws from a variety of…

An SH2 domain model of STAT5 in complex with phospho-peptides define "STAT5 Binding Signatures".

Science.gov (United States)

Gianti, Eleonora; Zauhar, Randy J

2015-05-01

The signal transducer and activator of transcription 5 (STAT5) is a member of the STAT family of proteins, implicated in cell growth and differentiation. STAT activation is regulated by phosphorylation of protein monomers at conserved tyrosine residues, followed by binding to phospho-peptide pockets and subsequent dimerization. STAT5 is implicated in the development of severe pathological conditions, including many cancer forms. However, nowadays a few STAT5 inhibitors are known, and only one crystal structure of the inactive STAT5 dimer is publicly available. With a view to enabling structure-based drug design, we have: (1) analyzed phospho-peptide binding pockets on SH2 domains of STAT5, STAT1 and STAT3; (2) generated a model of STAT5 bound to phospho-peptides; (3) assessed our model by docking against a class of known STAT5 inhibitors (Müller et al. in ChemBioChem 9:723-727, 2008); (4) used molecular dynamics simulations to optimize the molecular determinants responsible for binding and (5) proposed unique "Binding Signatures" of STAT5. Our results put in place the foundations to address STAT5 as a target for rational drug design, from sequence, structural and functional perspectives.

An SH2 domain model of STAT5 in complex with phospho-peptides define ``STAT5 Binding Signatures''

Science.gov (United States)

Gianti, Eleonora; Zauhar, Randy J.

2015-05-01

The signal transducer and activator of transcription 5 (STAT5) is a member of the STAT family of proteins, implicated in cell growth and differentiation. STAT activation is regulated by phosphorylation of protein monomers at conserved tyrosine residues, followed by binding to phospho-peptide pockets and subsequent dimerization. STAT5 is implicated in the development of severe pathological conditions, including many cancer forms. However, nowadays a few STAT5 inhibitors are known, and only one crystal structure of the inactive STAT5 dimer is publicly available. With a view to enabling structure-based drug design, we have: (1) analyzed phospho-peptide binding pockets on SH2 domains of STAT5, STAT1 and STAT3; (2) generated a model of STAT5 bound to phospho-peptides; (3) assessed our model by docking against a class of known STAT5 inhibitors (Müller et al. in ChemBioChem 9:723-727, 2008); (4) used molecular dynamics simulations to optimize the molecular determinants responsible for binding and (5) proposed unique "Binding Signatures" of STAT5. Our results put in place the foundations to address STAT5 as a target for rational drug design, from sequence, structural and functional perspectives.

African Americans: College Majors and Earnings. Fact Sheet

Science.gov (United States)

Carnevale, Anthony P.; Fasules, Megan L.; Porter, Andrea; Landis-Santos Jennifer

2016-01-01

Access to college for African Americans has increased, but African Americans are highly concentrated in lower-paying majors. The college major, which has critical economic consequences throughout life, reflects personal choices but also reflects the fact that African-American students are concentrated in open-access four-year institutions that…

Different Competitive Capacities of Stat4 and Stat6 Deficient CD4+ T Cells during Lymphophenia-Driven Proliferation

DEFF Research Database (Denmark)

Sanchez-Guajardo, Vanesa Maria; Borghans, J.A.M.; Marquez, M.-E.

2005-01-01

The outcome of an immune response relies on the competitive capacities acquired through differentiation of CD4ﰀ T cells into Th1 or Th2 effector cells. Because Stat4 and Stat6 proteins are implicated in the Th1 vs Th2 generation and maintenance, respectively, we compare in this study the kinetics...... of Stat4ﰐ/ﰐ and Stat6ﰐ/ﰐ CD4ﰀ T cells during competitive bone marrow reconstitution and lymphopenia-driven proliferation. After bone marrow transplantation, both populations reconstitute the peripheral T cell pools equally well. After transfer into lymphopenic hosts, wild-type and Stat6ﰐ/ﰐ CD4ﰀ T cells...... show a proliferation advantage, which is early associated with the expression of an active phospho-Stat4 and the down-regulation of Stat6. Despite these differences, Stat4- and Stat6-deficient T cells reach similar steady state numbers. However, when both Stat4ﰐ/ﰐ and Stat6ﰐ/ﰐ CD4ﰀ T cells...

Know How to Use Your Asthma Inhaler

Medline Plus

Full Text Available ... Surveillance Most Recent Asthma Data Most Recent Asthma State or Territory Data AsthmaStats Asthma as the Underlying ... Links Asthma’s Impact on the Nation Fact Sheet State Data Profiles (2011) Work-related Asthma NCHS Asthma ...

Kobuvirus VP3 protein restricts the IFN-β-triggered signaling pathway by inhibiting STAT2-IRF9 and STAT2-STAT2 complex formation

Energy Technology Data Exchange (ETDEWEB)

Peng, Qianqian; Lan, Xi; Wang, Chen [State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046 (China); Ren, Yujie; Yue, Ningning [College of Life Sciences, Wuhan University, Wuhan 430072 (China); Wang, Junyong [State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046 (China); Zhong, Bo [College of Life Sciences, Wuhan University, Wuhan 430072 (China); Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhu, Qiyun, E-mail: zhuqiyun@caas.cn [State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046 (China)

2017-07-15

Emerged porcine kobuvirus (PKV) has adversely affected the global swine industry since 2008, but the etiological biology of PKV is unclear. Screening PKV-encoded structural and non-structural proteins with a type I IFN-responsive luciferase reporter showed that PKV VP3 protein inhibited the IFN-β-triggered signaling pathway, resulting in the decrease of VSV-GFP replication. QPCR data showed that IFN-β downstream cytokine genes were suppressed without cell-type specificity as well. The results from biochemical experiments indicated that PKV VP3 associated with STAT2 and IRF9, and interfered with the formation of the STAT2-IRF9 and STAT2-STAT2 complex, impairing nuclear translocation of STAT2 and IRF9. Taken together, these data reveal a new mechanism for immune evasion of PKV. - Highlights: •PKV VP3 inhibits the IFN-β-triggered signaling pathway. •VP3 associates with STAT2 and IRF9. •VP3 blocks the STAT2-IRF9 nuclear translocation. •VP3 utilizes a novel strategy for innate immune evasion.

In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3

DEFF Research Database (Denmark)

Sommer, V H; Clemmensen, O J; Nielsen, O

2004-01-01

in the epidermal Pautrier abscesses associated with early stages of MF did not express activated STAT3. To address the role of STAT3 in survival/apoptosis, CTCL tumor cells from an advanced skin tumor were transfected with either wild-type STAT3 (STAT3wt) or dominant-negative STAT3 (STAT3D). Forced inducible...... expression of STAT3D triggered a significant increase in tumor cells undergoing apoptosis, whereas forced expression of STAT3wt or empty vector had no effect. In conclusion, a profound in vivo activation of STAT3 is observed in MF tumors but not in the early stages of MF. Moreover, STAT3 protects tumor cells...

Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population: a case-control association study of the STAT1-STAT4 region

Science.gov (United States)

Kawasaki, Aya; Ito, Ikue; Hikami, Koki; Ohashi, Jun; Hayashi, Taichi; Goto, Daisuke; Matsumoto, Isao; Ito, Satoshi; Tsutsumi, Akito; Koga, Minori; Arinami, Tadao; Graham, Robert R; Hom, Geoffrey; Takasaki, Yoshinari; Hashimoto, Hiroshi; Behrens, Timothy W; Sumida, Takayuki; Tsuchiya, Naoyuki

2008-01-01

Introduction Recent studies identified STAT4 (signal transducers and activators of transcription-4) as a susceptibility gene for systemic lupus erythematosus (SLE). STAT1 is encoded adjacently to STAT4 on 2q32.2-q32.3, upregulated in peripheral blood mononuclear cells from SLE patients, and functionally relevant to SLE. This study was conducted to test whether STAT4 is associated with SLE in a Japanese population also, to identify the risk haplotype, and to examine the potential genetic contribution of STAT1. To accomplish these aims, we carried out a comprehensive association analysis of 52 tag single nucleotide polymorphisms (SNPs) encompassing the STAT1-STAT4 region. Methods In the first screening, 52 tag SNPs were selected based on HapMap Phase II JPT (Japanese in Tokyo, Japan) data, and case-control association analysis was carried out on 105 Japanese female patients with SLE and 102 female controls. For associated SNPs, additional cases and controls were genotyped and association was analyzed using 308 SLE patients and 306 controls. Estimation of haplotype frequencies and an association study using the permutation test were performed with Haploview version 4.0 software. Population attributable risk percentage was estimated to compare the epidemiological significance of the risk genotype among populations. Results In the first screening, rs7574865, rs11889341, and rs10168266 in STAT4 were most significantly associated (P rs7574865) (P = 1.5 × 10-6). The association was stronger in subgroups of SLE with nephritis and anti-double-stranded DNA antibodies. Population attributable risk percentage was estimated to be higher in the Japanese population (40.2%) than in Americans of European descent (19.5%). Conclusions The same STAT4 risk allele is associated with SLE in Caucasian and Japanese populations. Evidence for a role of STAT1 in genetic susceptibility to SLE was not detected. The contribution of STAT4 for the genetic background of SLE may be greater in the

Development of a STAT3 reporter prostate cancer cell line for high throughput screening of STAT3 activators and inhibitors

International Nuclear Information System (INIS)

Chau, My N.; Banerjee, Partha P.

2008-01-01

STAT3 is constitutively activated in several cancers, including prostate cancer, and is therefore, a potential target for cancer therapy. DU-145 prostate cancer cells were stably co-transfected with STAT3 reporter and puromycin resistant plasmids to create a stable STAT3 reporter cell line that can be used for high throughput screening of STAT3 modulators. The applicability of this cell line was tested with two known activators and inhibitors of STAT3. As expected, EGF and IL-6 increased STAT3 reporter activity and enhanced the nuclear localization of phosphorylated STAT3 (pSTAT3); whereas Cucurbitacin I and AG490 decreased STAT3 reporter activity dose and time-dependently and reduced the localization of pSTAT3 in the nuclei of prostate cancer cells. Given the importance of STAT3 in cancer initiation and progression, the development of a stable STAT3 reporter cell line in prostate cancer cells provides a rapid, sensitive, and cost effective method for the screening of potential STAT3 modulators.

Stat1 activation attenuates IL-6 induced Stat3 activity but does not alter apoptosis sensitivity in multiple myeloma

Directory of Open Access Journals (Sweden)

Dimberg Lina Y

2012-07-01

Full Text Available Abstract Background Multiple myeloma (MM is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM. Methods To delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of the U-266-1970 MM cell line with a stable expression of the active mutant Stat1C were utilized. The influence of Stat1C constitutive transcriptional activation on endogenous Stat3 expression and activation, and the expression of apoptosis-related genes were analyzed. To determine whether Stat1 alone would be an important determinant in sensitizing MM cells to apoptosis, the U-266-1970-Stat1C cell line and control cells were exposed to high throughput compound screening (HTS. Results To explore the role of Stat1 in IFN mediated apoptosis sensitization of MM, we established sublines of the MM cell line U-266-1970 constitutively expressing the active mutant Stat1C. We found that constitutive nuclear localization and transcriptional activity of Stat1 was associated with an attenuation of IL-6-induced Stat3 activation and up-regulation of mRNA for the pro-apoptotic Bcl-2 protein family genes Harakiri, the short form of Mcl-1 and Noxa. However, Stat1 activation alone was not sufficient to sensitize cells to Fas-induced apoptosis. In a screening of > 3000 compounds including bortezomib, dexamethasone, etoposide, suberoylanilide hydroxamic acid (SAHA, geldanamycin (17-AAG, doxorubicin and thalidomide, we found that the drug response and IC50 in cells constitutively expressing active Stat1 was mainly unaltered. Conclusion We conclude that Stat1 alters IL-6

Stat1 activation attenuates IL-6 induced Stat3 activity but does not alter apoptosis sensitivity in multiple myeloma

International Nuclear Information System (INIS)

Dimberg, Lina Y; Nilsson, Kenneth; Öberg, Fredrik; Wiklund, Helena Jernberg; Dimberg, Anna; Ivarsson, Karolina; Fryknäs, Mårten; Rickardson, Linda; Tobin, Gerard; Ekman, Simon; Larsson, Rolf; Gullberg, Urban

2012-01-01

Multiple myeloma (MM) is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN) treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat)1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM. To delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of the U-266-1970 MM cell line with a stable expression of the active mutant Stat1C were utilized. The influence of Stat1C constitutive transcriptional activation on endogenous Stat3 expression and activation, and the expression of apoptosis-related genes were analyzed. To determine whether Stat1 alone would be an important determinant in sensitizing MM cells to apoptosis, the U-266-1970-Stat1C cell line and control cells were exposed to high throughput compound screening (HTS). To explore the role of Stat1 in IFN mediated apoptosis sensitization of MM, we established sublines of the MM cell line U-266-1970 constitutively expressing the active mutant Stat1C. We found that constitutive nuclear localization and transcriptional activity of Stat1 was associated with an attenuation of IL-6-induced Stat3 activation and up-regulation of mRNA for the pro-apoptotic Bcl-2 protein family genes Harakiri, the short form of Mcl-1 and Noxa. However, Stat1 activation alone was not sufficient to sensitize cells to Fas-induced apoptosis. In a screening of > 3000 compounds including bortezomib, dexamethasone, etoposide, suberoylanilide hydroxamic acid (SAHA), geldanamycin (17-AAG), doxorubicin and thalidomide, we found that the drug response and IC50 in cells constitutively expressing active Stat1 was mainly unaltered. We conclude that Stat1 alters IL-6 induced Stat3 activity and the expression of pro

STAT1 in cancer: friend or foe?

Science.gov (United States)

Zhang, Ying; Liu, Zhaoyong

2017-08-01

The first STAT family member, STAT1, is an essential component of interferon (IFN)-signaling, which mediates several cellular functions in response to stimulation by cytokines, growth factors, and hormones, such as the IFNs and IL-6. The role and significance of STAT1 in cancer biology have been studied for a decade. The majority of evidence shows that activating STAT1 plays a tumor suppressor role in cancer cells. Nevertheless, results from some experiments and clinical studies suggest that STAT1 also exerts tumor promoter effects under specific conditions. In some malignant phenotypes, STAT1 can function either as an oncoprotein or tumor suppressor in the same cell type, depending on the specific genetic background. Thus, the function of STAT1 in cancer biology remains a mystery. In this review, we discuss both the "friend" and "foe" features of STAT1 by summarizing its tumor suppressor or oncogenic functions and mechanisms. To explain how STAT1 may mediate its tumor suppressor effects, we discuss several possible mechanisms, one of which is linked to the role of STAT1β, an isoform of STAT1.

Analysis list: Stat3 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Stat3 Blood,Digestive tract,Neural + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u.../mm9/target/Stat3.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Stat3.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/target/Stat3.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Stat3.B...lood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Stat3.Digestive_trac...t.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Stat3.Neural.tsv http://dbarchive.biosciencedbc.jp

FastStats: Child Health

Science.gov (United States)

... Women’s Health State and Territorial Data Reproductive Health Contraceptive Use Infertility Reproductive Health Notice Regarding FastStats Mobile ... table 6 [PDF – 2.7 MB] Related FastStats Adolescent Health ADHD Asthma Infant Health More data: reports ...

Herpes Can Happen to Anyone: Share Facts, Not Fears

Science.gov (United States)

... promiscuous. Links Oral Herpes Sexually Transmitted Diseases Genital Herpes (CDC) Genital Herpes Fact Sheet (CDC) What You Need to Know About Genital Herpes Video (CDC) References Vaccination to Reduce Reactivation of ...

Structural and functional characterization of salmon STAT1, STAT2 and IRF9 homologs sheds light on interferon signaling in teleosts

Directory of Open Access Journals (Sweden)

Mehrdad Sobhkhez

2014-01-01

Full Text Available Mammalian IRF9 and STAT2, together with STAT1, form the ISGF3 transcription factor complex, which is critical for type I interferon (IFN-induced signaling, while IFNγ stimulation is mediated by homodimeric STAT1 protein. Teleost fish are known to possess most JAK and STAT family members, however, description of their functional activity in lower vertebrates is still scarce. In the present study we have identified two different STAT2 homologs and one IRF9 homolog from Atlantic salmon (Salmo salar. Both proteins have domain-like structures with functional motifs that are similar to higher vertebrates, suggesting that they are orthologs to mammalian STAT2 and IRF9. The two identified salmon STAT2s, named STAT2a and STAT2b, showed high sequence identity but were divergent in their transactivation domain (TAD. Like STAT1, ectopically expressed STAT2a and b were shown to be tyrosine phosphorylated by type I IFNs and, interestingly, also by IFNγ. Microscopy analyses demonstrated that STAT2 co-localized with STAT1a in the cytoplasm of unstimulated cells, while IFNa1 and IFNγ stimulation seemed to favor their nuclear localization. Overexpression of STAT2a or STAT2b together with STAT1a activated a GAS-containing reporter gene construct in IFNγ-stimulated cells. The highest induction of GAS promoter activation was found in IFNγ-stimulated cells transfected with IRF9 alone. Taken together, these data suggest that salmon STAT2 and IRF9 may have a role in IFNγ-induced signaling and promote the expression of GAS-driven genes in bony fish. Since mammalian STAT2 is primarily an ISGF3 component and not involved in IFNγ signaling, our finding features a novel role for STAT2 in fish.

Communicacion Expresiva: Como los ninos nos envian mensajes [and] Comunicacion Receptiva: Como los ninos entienden nuestros mensajes [and] Interacciones de Comunicacion: Hacen falta dos. Hojas informativa de DB-LINK (Communication Interactions: It Takes Two [and] Receptive Communication: How Children Understand Your Messages to Them [and] Expressive Communication: How Children Send Their Messages to You. DB-LINK Fact Sheets).

Science.gov (United States)

Stremel, Kathleen

This document consists of three separately published fact sheets combined here because of the close relationship of their subject matter. The first fact sheet, "Communication Interactions: It Takes Two" (Kathleen Stremel), defines communication; suggests ways to find opportunities for interactive communication; offers specific suggestions for…

Enhancing Tribal Energy Security and Clean Energy (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2013-07-01

This fact provides information on the Strategic Technical Assistance Response Team (START) Program, a U.S. Department of Energy Office of Indian Energy Policy and Programs (DOE-IE) initiative to provide technical expertise to support the development of next-generation energy projects in Indian Country.

Antitumorigenic potential of STAT3 alternative splicing modulation.

Science.gov (United States)

Zammarchi, Francesca; de Stanchina, Elisa; Bournazou, Eirini; Supakorndej, Teerawit; Martires, Kathryn; Riedel, Elyn; Corben, Adriana D; Bromberg, Jacqueline F; Cartegni, Luca

2011-10-25

Signal transducer and activator of transcription 3 (STAT3) plays a central role in the activation of multiple oncogenic pathways. Splicing variant STAT3β uses an alternative acceptor site within exon 23 that leads to a truncated isoform lacking the C-terminal transactivation domain. Depending on the context, STAT3β can act as a dominant-negative regulator of transcription and promote apoptosis. We show that modified antisense oligonucleotides targeted to a splicing enhancer that regulates STAT3 exon 23 alternative splicing specifically promote a shift of expression from STAT3α to STAT3β. Induction of endogenous STAT3β leads to apoptosis and cell-cycle arrest in cell lines with persistent STAT3 tyrosine phosphorylation compared with total STAT3 knockdown obtained by forced splicing-dependent nonsense-mediated decay (FSD-NMD). Comparison of the molecular effects of splicing redirection to STAT3 knockdown reveals a unique STAT3β signature, with a down-regulation of specific targets (including lens epithelium-derived growth factor, p300/CBP-associated factor, CyclinC, peroxisomal biogenesis factor 1, and STAT1β) distinct from canonical STAT3 targets typically associated with total STAT3 knockdown. Furthermore, similar in vivo redirection of STAT3 alternative splicing leads to tumor regression in a xenograft cancer model, demonstrating how pharmacological manipulation of a single key splicing event can manifest powerful antitumorigenic properties and validating endogenous splicing reprogramming as an effective cancer therapeutic approach.

BrightStat.com: free statistics online.

Science.gov (United States)

Stricker, Daniel

2008-10-01

Powerful software for statistical analysis is expensive. Here I present BrightStat, a statistical software running on the Internet which is free of charge. BrightStat's goals, its main capabilities and functionalities are outlined. Three different sample runs, a Friedman test, a chi-square test, and a step-wise multiple regression are presented. The results obtained by BrightStat are compared with results computed by SPSS, one of the global leader in providing statistical software, and VassarStats, a collection of scripts for data analysis running on the Internet. Elementary statistics is an inherent part of academic education and BrightStat is an alternative to commercial products.

A molecular model for the differential activation of STAT3 and STAT6 by the herpesviral oncoprotein tip.

Directory of Open Access Journals (Sweden)

Eman Dey Mazumder

Full Text Available Constitutive STAT signaling provides growth promoting signals in many forms of malignancy. We performed molecular modeling and molecular dynamics studies of the interaction between the regulatory Src homology 2 (SH2 domains of STAT3 and 6 with phosphorylated peptides of the herpesviral oncoprotein Tip, which facilitates Src kinase mediated STAT-activation and T cell proliferation. The studies give insight into the ligand binding specificity of the STAT SH2 domains and provide the first model for the differential activation of STAT3 or STAT6 by two distinct regions of the viral Tip protein. The biological relevance of the modeled interactions was then confirmed by activation studies using corresponding recombinant oncoproteins, and finally by respective recombinant viruses. The functional data give experimental validation of the molecular dynamics study, and provide evidence for the involvement of STAT6 in the herpesvirus induced T cell proliferation.

Activation of Stat3 in renal tumors.

Science.gov (United States)

Guo, Charles; Yang, Guanyu; Khun, Kyle; Kong, Xiantian; Levy, David; Lee, Peng; Melamed, Jonathan

2009-02-28

Signal transducer and activator of transcription 3 (Stat3) plays a vital role in signal transduction pathways that mediate transformation and inhibit apoptosis. Oncogenic Stat3 is persistently activated in several human cancers and transformed cell lines. Previous studies indicate activation of Stat3 in renal cell carcinoma (RCC). However, the detailed characterization of the Stat3 expression pattern in different histologic types of RCC is lacking. We have analyzed the immunoprofile of activated or phosphorylated Stat3 (pStat3) in a tissue microarray of renal tumors of different histologic types, including 42 cases of conventional clear cell type, 24 chromophobe, and 7 papillary, 15 oncocytoma, 7 urothelial carcinoma and 21 normal kidney tissues using an anti-pStat3 antibody (recognizes only activated STAT3). pStat3 nuclear staining was observed in 25 of 42 conventional clear cell RCC (59.5 %), 8 of 24 chromophobe RCC (33.3%), 4 of 7 papillary RCC (57.1%). In the other tumor groups, 4 of 15 oncocytomas (26.7%) and 6 of 7 urothelial carcinomas (85.7%) showed positive nuclear staining. Weak nuclear immunoreactivity for pStat3 was seen in 4 of 21 cases of non-neoplastic kidney tissue (19.0%). The extent of Stat3 activation as determined by nuclear expression of its phosphorylated form is increased in histologic types of renal tumors with greater malignant potential, specifically conventional clear cell RCC, papillary RCC and urothelial carcinoma, only slightly increased in chromophobe RCC, and not increased in oncocytoma. These results suggest a role of Stat3 activation in different types of renal neoplasia, possibly serving as a prognostic marker or therapeutic target.

STAT3 in Cancer—Friend or Foe?

Science.gov (United States)

Zhang, Hai-Feng; Lai, Raymond

2014-01-01

The roles and significance of STAT3 in cancer biology have been extensively studied for more than a decade. Mounting evidence has shown that constitutive activation of STAT3 is a frequent biochemical aberrancy in cancer cells, and this abnormality directly contributes to tumorigenesis and shapes many malignant phenotypes in cancer cells. Nevertheless, results from more recent experimental and clinicopathologic studies have suggested that STAT3 also can exert tumor suppressor effects under specific conditions. Importantly, some of these studies have demonstrated that STAT3 can function either as an oncoprotein or a tumor suppressor in the same cell type, depending on the specific genetic background or presence/absence of specific coexisting biochemical defects. Thus, in the context of cancer biology, STAT3 can be a friend or foe. In the first half of this review, we will highlight the “evil” features of STAT3 by summarizing its oncogenic functions and mechanisms. The differences between the canonical and non-canonical pathway will be highlighted. In the second half, we will summarize the evidence supporting that STAT3 can function as a tumor suppressor. To explain how STAT3 may mediate its tumor suppressor effects, we will discuss several possible mechanisms, one of which is linked to the role of STAT3β, one of the two STAT3 splicing isoforms. Taken together, it is clear that the roles of STAT3 in cancer are multi-faceted and far more complicated than one appreciated previously. The new knowledge has provided us with new approaches and strategies when we evaluate STAT3 as a prognostic biomarker or therapeutic target. PMID:24995504

STAT3 in Cancer—Friend or Foe?

Energy Technology Data Exchange (ETDEWEB)

Zhang, Hai-Feng [Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 1Z2 (Canada); The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong (China); Lai, Raymond, E-mail: rlai@ualberta.ca [Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 1Z2 (Canada)

2014-07-03

The roles and significance of STAT3 in cancer biology have been extensively studied for more than a decade. Mounting evidence has shown that constitutive activation of STAT3 is a frequent biochemical aberrancy in cancer cells, and this abnormality directly contributes to tumorigenesis and shapes many malignant phenotypes in cancer cells. Nevertheless, results from more recent experimental and clinicopathologic studies have suggested that STAT3 also can exert tumor suppressor effects under specific conditions. Importantly, some of these studies have demonstrated that STAT3 can function either as an oncoprotein or a tumor suppressor in the same cell type, depending on the specific genetic background or presence/absence of specific coexisting biochemical defects. Thus, in the context of cancer biology, STAT3 can be a friend or foe. In the first half of this review, we will highlight the “evil” features of STAT3 by summarizing its oncogenic functions and mechanisms. The differences between the canonical and non-canonical pathway will be highlighted. In the second half, we will summarize the evidence supporting that STAT3 can function as a tumor suppressor. To explain how STAT3 may mediate its tumor suppressor effects, we will discuss several possible mechanisms, one of which is linked to the role of STAT3β, one of the two STAT3 splicing isoforms. Taken together, it is clear that the roles of STAT3 in cancer are multi-faceted and far more complicated than one appreciated previously. The new knowledge has provided us with new approaches and strategies when we evaluate STAT3 as a prognostic biomarker or therapeutic target.

Facts about food irradiation: Nutritional quality of irradiated foods

International Nuclear Information System (INIS)

1991-01-01

This fact sheet briefly considers the nutritional value of irradiated foods. Micronutrients, especially vitamins, are sensitive to any food processing method, but irradiation does not cause any special nutritional problems in food. 4 refs

Fuels planning: science synthesis and integration; forest structure and fire hazard fact sheet 06: Guide to fuel treatments in dry forests of the Western United States: assessing forest structure and fire hazard

Science.gov (United States)

Rocky Mountain Research Station USDA Forest Service

2005-01-01

The Guide to Fuel Treatments analyzes a range of potential silvicultural thinnings and surface fuel treatments for 25 representative dry-forest stands in the Western United States. The guide provides quantitative guidelines and visualization for treatment based on scientific principles identified for reducing potential crown fires. This fact sheet identifies the...

Inhibition of STAT3 reduces astrocytoma cell invasion and constitutive activation of STAT3 predicts poor prognosis in human astrocytoma.

Directory of Open Access Journals (Sweden)

Qinchuan Liang

Full Text Available Astrocytoma cells characteristically possess high invasion potentials. Recent studies have revealed that knockdown of signal transducers and activators of transcription 3 (STAT3 expression by RNAi induces apoptosis in astrocytoma cell. Nevertheless, the distinct roles of STAT3 in astrocytoma's invasion and recurrence have not been elucidated. In this study, we silenced STAT3 using Small interfering RNAs in two human glioblastoma multiforme (GBM cell lines (U251 and U87, and investigated the effect on GBM cell adhesion and invasion. Our results demonstrate that disruption of STAT3 inhibits GBM cell's adhesion and invasion. Knockdown of STAT3 significantly increased E-cadherin but decreased N-cadherin, vascular endothelial growth factor, matrix metalloproteinase 2 and matrix metalloproteinase 9. Additionally, expression of pSTAT3(Tyr705 correlates with astrocytoma WHO classification, Karnofsky performance status scale score, tumor recurrence and survival. Furthermore, pSTAT3(Tyr705 is a significant prognostic factor in astrocytoma. In conclusion, STAT3 may affect astrocytoma invasion, expression of pSTAT3(Tyr705 is a significant prognostic factor in tumor recurrence and overall survival in astrocytoma patients. Therefore, STAT3 may provide a potential target for molecular therapy in human astrocytoma, and pSTAT3(Tyr705could be an important biomarker for astrocytoma prognosis.

A novel STAT inhibitor, OPB-31121, has a significant antitumor effect on leukemia with STAT-addictive oncokinases

International Nuclear Information System (INIS)

Hayakawa, F; Sugimoto, K; Harada, Y; Hashimoto, N; Ohi, N; Kurahashi, S; Naoe, T

2013-01-01

Signal transduction and activator of transcription (STAT) proteins are extracellular ligand-responsive transcription factors that mediate cell proliferation, apoptosis, differentiation, development and the immune response. Aberrant signals of STAT induce uncontrolled cell proliferation and apoptosis resistance and are strongly involved in cancer. STAT has been identified as a promising target for antitumor drugs, but to date most trials have not been successful. Here, we demonstrated that a novel STAT inhibitor, OPB-31121, strongly inhibited STAT3 and STAT5 phosphorylation without upstream kinase inhibition, and induced significant growth inhibition in various hematopoietic malignant cells. Investigation of various cell lines suggested that OPB-31121 is particularly effective against multiple myeloma, Burkitt lymphoma and leukemia harboring BCR–ABL, FLT3/ITD and JAK2 V617F, oncokinases with their oncogenicities dependent on STAT3/5. Using an immunodeficient mouse transplantation system, we showed the significant antitumor effect of OPB-31121 against primary human leukemia cells harboring these aberrant kinases and its safety for normal human cord blood cells. Finally, we demonstrated a model to overcome drug resistance to upstream kinase inhibitors with a STAT inhibitor. These results suggested that OPB-31121 is a promising antitumor drug. Phase I trials have been performed in Korea and Hong Kong, and a phase I/II trial is underway in Japan

Nuclear relocation of STAT6 reliably predicts NAB2-STAT6 fusion for the diagnosis of solitary fibrous tumour.

Science.gov (United States)

Koelsche, Christian; Schweizer, Leonille; Renner, Marcus; Warth, Arne; Jones, David T W; Sahm, Felix; Reuss, David E; Capper, David; Knösel, Thomas; Schulz, Birte; Petersen, Iver; Ulrich, Alexis; Renker, Eva Kristin; Lehner, Burkhard; Pfister, Stefan M; Schirmacher, Peter; von Deimling, Andreas; Mechtersheimer, Gunhild

2014-11-01

Nuclear relocation of STAT6 has been shown in tumours with NAB2-STAT6 fusion, and has been proposed as an ancillary marker for the diagnosis of solitary fibrous tumours (SFTs). The aim of this study was to verify the utility of STAT6 immunohistology in diagnosing SFT. A total of 689 formalin-fixed paraffin-embedded tumours comprising 35 pleural SFTs and 654 other mesenchymal tumours were investigated for STAT6 expression using immunohistochemistry. Nine dedifferentiated liposarcomas (DDLSs) and five SFTs were also examined for the presence of NAB2-STAT6 fusion at the protein level using the proximity ligation assay (PLA), and for copy number variants (CNVs) with the Illumina Infinium Human Methylation450 array. Thirty-four of 35 SFTs showed strong nuclear STAT6 expression. Furthermore, five of 68 DDLSs, two of 130 undifferentiated pleomorphic sarcomas and one of 63 cases of nodular fasciitis showed moderate to strong nuclear STAT6 expression. The PLA indicated the presence of NAB2-STAT6 fusion protein in SFTs, but signal was also detected in some DDLSs. Copy number analysis showed an overall low frequency of chromosomal imbalances in SFTs, but complex karyotypes in DDLSs, including amplification of STAT6 and MDM2 loci. The detection of nuclear relocation of STAT6 with immunohistochemistry is a characteristic of SFTs, and may serve as a diagnostic marker that indicates NAB2-STAT6 fusion and helps to discriminate SFTs from histological mimics. © 2014 John Wiley & Sons Ltd.

Facts about food irradiation: Chemical changes in irradiated foods

International Nuclear Information System (INIS)

1991-01-01

This fact sheet addresses the safety of irradiated food. The irradiation process produces very little chemical change in food, and laboratory experiments have shown no harmful effects in animals fed with irradiated milk powder. 3 refs

RooStats for Searches

CERN Document Server

Schott, Gregory

2011-01-01

The RooStats toolkit, which is distributed with the ROOT software package, provides a large collection of software tools that implement statistical methods commonly used by the High Energy Physics community. The toolkit is based on RooFit, a high-level data analysis modeling package that implements various methods of statistical data analysis. RooStats enforces a clear mapping of statistical concepts to C++ classes and methods and emphasizes the ability to easily combine analyses within and across experiments. We present an overview of the RooStats toolkit, describe some of the methods used for hypothesis testing and estimation of confidence intervals and finally discuss some of the latest developments.

STAT3 Activities and Energy Metabolism: Dangerous Liaisons

Energy Technology Data Exchange (ETDEWEB)

Camporeale, Annalisa, E-mail: annalisa.camporeale@unito.it [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy); Demaria, Marco [Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945 (United States); Monteleone, Emanuele [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy); Giorgi, Carlotta [Department of Experimental and Diagnostic Medicine, Section of General Pathology, Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara 44121 (Italy); Wieckowski, Mariusz R. [Nencki Institute of Experimental Biology, Department of Biochemistry, Pasteur Str. 3, Warsaw 02-093 (Poland); Pinton, Paolo [Department of Experimental and Diagnostic Medicine, Section of General Pathology, Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara 44121 (Italy); Poli, Valeria, E-mail: annalisa.camporeale@unito.it [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy)

2014-07-31

STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3{sup C/C}) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3{sup C/C} MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3{sup C/C} MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms.

STAT3 Activities and Energy Metabolism: Dangerous Liaisons

International Nuclear Information System (INIS)

Camporeale, Annalisa; Demaria, Marco; Monteleone, Emanuele; Giorgi, Carlotta; Wieckowski, Mariusz R.; Pinton, Paolo; Poli, Valeria

2014-01-01

STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3 C/C ) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3 C/C MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3 C/C MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms

Sheet pinch devices

International Nuclear Information System (INIS)

Anderson, O.A.; Baker, W.R.; Ise, J. Jr.; Kunkel, W.B.; Pyle, R.V.; Stone, J.M.

1958-01-01

Three types of sheet-like discharges are being studied at Berkeley. The first of these, which has been given the name 'Triax', consists of a cylindrical plasma sleeve contained between two coaxial conducting cylinders A theoretical analysis of the stability of the cylindrical sheet plasma predicts the existence of a 'sausage-mode' instability which is, however, expected to grow more slowly than in the case of the unstabilized linear pinch (by the ratio of the radial dimensions). The second pinch device employs a disk shaped discharge with radial current guided between flat metal plates, this configuration being identical to that of the flat hydromagnetic capacitor without external magnetic field. A significant feature of these configurations is the absence of a plasma edge, i.e., there are no regions of sharply curved magnetic field lines anywhere in these discharges. The importance of this fact for stability is not yet fully investigated theoretically. As a third configuration a rectangular, flat pinch tube has been constructed, and the behaviour of a flat plasma sheet with edges is being studied experimentally

Facts about food irradiation: Packaging of irradiated foods

International Nuclear Information System (INIS)

1991-01-01

This fact sheet considers the effects on packaging materials of food irradiation. Extensive research has shown that almost all commonly used food packaging materials toted are suitable for use. Furthermore, many packaging materials are themselves routinely sterilized by irradiation before being used. 2 refs

Complex world-sheets from N=2 strings

International Nuclear Information System (INIS)

Barbon, J.L.F.

1996-01-01

We study some properties of target space strings constructed from (2,1) heterotic strings. We argue that world-sheet complexification is a general property of the bosonic sector of such target world-sheets. We give a target space interpretation of this fact and relate it to the non-gaussian nature of free string field theory. We provide several one-loop calculations supporting the stringy construction of critical world-sheets in terms of (2,1) models. Using finite-temperature boundary conditions in the underlying (2,1) string we obtain non-chiral target space spin structures, and point out some of the problems arising for chiral spin structures, such as the heterotic world-sheet. To this end, we study the torus partition function of the corresponding asymmetric orbifold of the (2,1) string. (orig.)

Stats means business

CERN Document Server

Buglear, John

2010-01-01

Stats Means Business is an introductory textbook written for Business, Hospitality and Tourism students who take modules on Statistics or Quantitative research methods. Recognising that most users of this book will have limited if any grounding in the subject, this book minimises technical language, provides clear definition of key terms, and gives emphasis to interpretation rather than technique.Stats Means Business enables readers to:appreciate the importance of statistical analysis in business, hospitality and tourism understand statis

Facts about food irradiation: Status and trends

International Nuclear Information System (INIS)

1991-01-01

This fact sheet introduces the concept of irradiating food to reduce post-harvest losses from infestation, contamination and spoilage, to lower the incidence of foodborne diseases and to assist international trade in food products by offering an alternative to fumigation or some other treatments that may not be acceptable to the importing countries

Increased STAT1 signaling in endocrine-resistant breast cancer.

Directory of Open Access Journals (Sweden)

Rui Huang

Full Text Available Proteomic profiling of the estrogen/tamoxifen-sensitive MCF-7 cell line and its partially sensitive (MCF-7/LCC1 and fully resistant (MCF-7/LCC9 variants was performed to identify modifiers of endocrine sensitivity in breast cancer. Analysis of the expression of 120 paired phosphorylated and non-phosphorylated epitopes in key oncogenic and tumor suppressor pathways revealed that STAT1 and several phosphorylated epitopes (phospho-STAT1(Tyr701 and phospho-STAT3(Ser727 were differentially expressed between endocrine resistant and parental controls, confirmed by qRT-PCR and western blotting. The STAT1 inhibitor EGCG was a more effective inhibitor of the endocrine resistant MCF-7/LCC1 and MCF-7/LCC9 lines than parental MCF-7 cells, while STAT3 inhibitors Stattic and WP1066 were equally effective in endocrine-resistant and parental lines. The effects of the STAT inhibitors were additive, rather than synergistic, when tested in combination with tamoxifen in vitro. Expression of STAT1 and STAT3 were measured by quantitative immunofluorescence in invasive breast cancers and matched lymph nodes. When lymph node expression was compared to its paired primary breast cancer expression, there was greater expression of cytoplasmic STAT1 (∼3.1 fold, phospho-STAT3(Ser727 (∼1.8 fold, and STAT5 (∼1.5 fold and nuclear phospho-STAT3(Ser727 (∼1.5 fold in the nodes. Expression levels of STAT1 and STAT3 transcript were analysed in 550 breast cancers from publicly available gene expression datasets (GSE2990, GSE12093, GSE6532. When treatment with tamoxifen was considered, STAT1 gene expression was nearly predictive of distant metastasis-free survival (DMFS, log-rank p = 0.067, while STAT3 gene expression was predictive of DMFS (log-rank p<0.0001. Analysis of STAT1 and STAT3 protein expression in a series of 546 breast cancers also indicated that high expression of STAT3 protein was associated with improved survival (DMFS, p = 0.006. These results suggest

Dual inhibition of STAT1 and STAT3 activation downregulates expression of PD-L1 in human breast cancer cells.

Science.gov (United States)

Sasidharan Nair, Varun; Toor, Salman M; Ali, Bassam R; Elkord, Eyad

2018-05-02

Breast cancer is the most commonly diagnosed cancer, and it is a leading cause of cancer-related deaths in females worldwide. Triple-negative breast cancer (TNBC) constitutes 15% of breast cancer and shows distinct metastasis profiles with poor prognosis. Strong PD-L1 expression has been observed in some tumors, supporting their escape from immune surveillance. Targeting PD-L1 could be a promising therapeutic approach in breast cancer patients. We investigated potential molecular mechanisms for constitutive expression of PD-L1 by inhibiting upstream STAT1 and STAT3 signals. PD-L1 expression in three breast cancer cell lines was measured using quantitative PCR and western blotting. Activation of STAT1 and STAT3 was blocked using pharmacological inhibitors and siRNA. The mechanism underlying the constitutive expression of PD-L1 was investigated using ChIP and co-immunoprecipitation assays. We found that individual inhibition of STAT1 and STAT3 activation partially downregulated PD-L1, while combined inhibition completely downregulated PD-L1 expression. Moreover, our results suggest that pSTAT1-pSTAT3 dimerize in cytosol and translocate to the nucleus, where they bind to PD-L1 promoter and induce PD-L1 expression. These findings provide a rationale for combined targeting of STAT1 and STAT3 for the development of immune-based cancer therapies for down regulation of PD-L1 expression.

Active Components with Inhibitory Activities on IFN-γ/STAT1 and IL-6/STAT3 Signaling Pathways from Caulis Trachelospermi

Directory of Open Access Journals (Sweden)

Xiao-Ting Liu

2014-08-01

Full Text Available Initial investigation for new active herbal extract with inhibiting activity on JAK/STAT signaling pathway revealed that the extract of Caulis Trachelospermi, which was separated by 80% alcohol extraction and subsequent HP-20 macroporous resin column chromatography, was founded to strongly inhibit IFN-γ-induced STAT1-responsive luciferase activity (IFN-γ/STAT1 with IC50 value of 2.43 μg/mL as well as inhibiting IL-6-induced STAT3-responsive luciferase activity (IL-6/STAT3 with IC50 value of 1.38 μg/mL. Subsequent study on its active components led to the isolation and identification of two new dibenzylbutyrolactone lignans named 4-demethyltraxillaside (1 and nortrachelogenin 4-O-β-d-glucopyranoside (2, together with six known compounds. The lignan compounds 1–4 together with other lignan compounds isolated in previous study were tested the activities on IFN-γ/STAT1 and IL-6/STAT3 pathways. The following result showed that the main components trachelogenin and arctigenin had corresponding activities on IFN-γ/STAT1 pathway with IC50 values of 3.14 μM and 9.46 μM as well as trachelogenin, arctigenin and matairesinol strongly inhibiting IL-6/STAT3 pathway with IC50 values of 3.63 μM, 6.47 μM and 2.92 μM, respectively.

Facts about food irradiation: Irradiation and food additives and residues

International Nuclear Information System (INIS)

1991-01-01

This fact sheet considers the issue of the irradiation of food containing food additives or pesticide residues. The conclusion is that there is no health hazard posed by radiolytic products of pesticides or food additives. 1 ref

Cisplatin ototoxicity involves cytokines and STAT6 signaling network

Institute of Scientific and Technical Information of China (English)

Hyung-Jin Kim; Jeong-Dug Sul; Channy Park; Sang-Young Chung; Sung-Kyun Moon; David J Lim; Hong-Seob So; Raekil Park; Gi-Su Oh; Jeong-Han Lee; Ah-Ra Lyu; Hye-Min Ji; Sang-Heon Lee; Jeho Song; Sung-Joo Park; Yong-Ouk You

2011-01-01

We herein investigated the role of the STAT signaling cascade in the production of pro-inflammatory cytokines and cisplatin ototoxicity. A significant hearing impairment caused by cisplatin injection was observed in Balb/c (wild type,WT) and STAT4-/-,but not in STAT6-/- mice. Moreover,the expression levels of the protein and mRNA of proinflammatory cytokines,including TNF-α,IL-1β,and IL-6,were markedly increased in the serum and cochlea of WT and STAT4+,but not STAT6-/- mice. Organotypic culture revealed that the shape of stereocilia bundles and arrays of sensory hair cell layers in the organ of Corti from STAT6-/- mice were intact after treatment with cisplatin,whereas those from WT and STAT4-/- mice were highly distorted and disarrayed after the treatment. Cisplatin induced the phosphorylation of STAT6 in HEI-OC1 auditory cells,and the knockdown of STAT6 by STAT6-specific siRNA significantly protected HEI-OC1 auditory cells from cisplatin-induced cell death and inhibited pro-inflammatory cytokine production. We further demonstrated that IL-4 and IL-13 induced by cisplatin modulated the phosphorylation of STAT6 by binding with IL-4 receptor alpha and IL-13Rα1. These findings suggest that STAT6 signaling plays a pivotal role in cisplatin-mediated pro-inflammatory cytokine production and ototoxicity.

Facts about food irradiation: Food irradiation costs

International Nuclear Information System (INIS)

1991-01-01

This fact sheet gives the cost of a typical food irradiation facility (US $1 million to US $3 million) and of the food irradiation process (US $10-15 per tonne for low-dose applications; US $100-250 per tonne for high-dose applications). These treatments also bring consumer benefits in terms of availability, storage life and improved hygiene. 2 refs

Biologic consequences of Stat1-independent IFN signaling

Science.gov (United States)

Gil, M. Pilar; Bohn, Erwin; O'Guin, Andrew K.; Ramana, Chilakamarti V.; Levine, Beth; Stark, George R.; Virgin, Herbert W.; Schreiber, Robert D.

2001-01-01

Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNγ functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now demonstrate that both IFNγ and IFNα/β regulate proliferative responses in cells of the mononuclear phagocyte lineage derived from Stat1-null mice. Using both representational difference analysis and gene arrays, we show that IFNγ exerts its Stat1-independent actions on mononuclear phagocytes by regulating the expression of many genes. This result was confirmed by monitoring changes in expression and function of the corresponding gene products. Regulation of the expression of these genes requires the IFNγ receptor and Jak1. The physiologic relevance of IFN-dependent, Stat1-independent signaling was demonstrated by monitoring antiviral responses in Stat1-null mice. Thus, the IFN receptors engage alternative Stat1-independent signaling pathways that have important physiological consequences. PMID:11390995

Constitutive activation of a slowly migrating isoform of Stat3 in mycosis fungoides: tyrphostin AG490 inhibits Stat3 activation and growth of mycosis fungoides tumor cell lines

DEFF Research Database (Denmark)

Nielsen, M; Kaltoft, K; Nordahl, M

1997-01-01

. Jaks link cytokine receptors to Stats, and abnormal Jak/Stat signaling has been observed in some hemopoietic cancers. In MF tumor cells, a slowly migrating isoform of Stat3, Stat3(sm), was found to be constitutively activated, i.e., (i) Stat3(sm) was constitutively phosphorylated on tyrosine residues...... specific. Thus, neither the fast migrating isoform of Stat3 (Stat3(fm)) nor other Stats (Stat1, Stat2, and Stat4 through Stat6) were constitutively activated. The Jak kinase inhibitor, tyrphostin AG490, blocked the constitutive activation of Stat3(sm) and inhibited spontaneous as well as interleukin 2...

Intracellular expression of IRF9 Stat fusion protein overcomes the defective Jak-Stat signaling and inhibits HCV RNA replication

Directory of Open Access Journals (Sweden)

Balart Luis A

2010-10-01

Full Text Available Abstract Interferon alpha (IFN-α binds to a cell surface receptor that activates the Jak-Stat signaling pathway. A critical component of this pathway is the translocation of interferon stimulated gene factor 3 (a complex of three proteins Stat1, Stat2 and IRF9 to the nucleus to activate antiviral genes. A stable sub-genomic replicon cell line resistant to IFN-α was developed in which the nuclear translocation of Stat1 and Stat2 proteins was prevented due to the lack of phosphorylation; whereas the nuclear translocation of IRF9 protein was not affected. In this study, we sought to overcome defective Jak-Stat signaling and to induce an antiviral state in the IFN-α resistant replicon cell line by developing a chimera IRF9 protein fused with the trans activating domain (TAD of either a Stat1 (IRF9-S1C or Stat2 (IRF9-S2C protein. We show here that intracellular expression of fusion proteins using the plasmid constructs of either IRF9-S1C or IRF9-S2C, in the IFN-α resistant cells, resulted in an increase in Interferon Stimulated Response Element (ISRE luciferase promoter activity and significantly induced HLA-1 surface expression. Moreover, we show that transient transfection of IRF9-S1C or IRF9-S2C plasmid constructs into IFN-α resistant replicon cells containing sub-genomic HCV1b and HCV2a viruses resulted in an inhibition of viral replication and viral protein expression independent of IFN-α treatment. The results of this study indicate that the recombinant fusion proteins of IRF9-S1C, IRF9-S2C alone, or in combination, have potent antiviral properties against the HCV in an IFN-α resistant cell line with a defective Jak-Stat signaling.

JAK/Stat signaling regulates heart precursor diversification in Drosophila

Science.gov (United States)

Johnson, Aaron N.; Mokalled, Mayssa H.; Haden, Tom N.; Olson, Eric N.

2011-01-01

Intercellular signal transduction pathways regulate the NK-2 family of transcription factors in a conserved gene regulatory network that directs cardiogenesis in both flies and mammals. The Drosophila NK-2 protein Tinman (Tin) was recently shown to regulate Stat92E, the Janus kinase (JAK) and Signal transducer and activator of transcription (Stat) pathway effector, in the developing mesoderm. To understand whether the JAK/Stat pathway also regulates cardiogenesis, we performed a systematic characterization of JAK/Stat signaling during mesoderm development. Drosophila embryos with mutations in the JAK/Stat ligand upd or in Stat92E have non-functional hearts with luminal defects and inappropriate cell aggregations. Using strong Stat92E loss-of-function alleles, we show that the JAK/Stat pathway regulates tin expression prior to heart precursor cell diversification. tin expression can be subdivided into four phases and, in Stat92E mutant embryos, the broad phase 2 expression pattern in the dorsal mesoderm does not restrict to the constrained phase 3 pattern. These embryos also have an expanded pericardial cell domain. We show the E(spl)-C gene HLHm5 is expressed in a pattern complementary to tin during phase 3 and that this expression is JAK/Stat dependent. In addition, E(spl)-C mutant embryos phenocopy the cardiac defects of Stat92E embryos. Mechanistically, JAK/Stat signals activate E(spl)-C genes to restrict Tin expression and the subsequent expression of the T-box transcription factor H15 to direct heart precursor diversification. This study is the first to characterize a role for the JAK/Stat pathway during cardiogenesis and identifies an autoregulatory circuit in which tin limits its own expression domain. PMID:21965617

Asthma and Environment Fact Sheet for Parents and Schools. Revised

Science.gov (United States)

Healthy Schools Network, Inc., 2012

2012-01-01

Important facts about asthma and the environment include: (1) Asthma has reached epidemic proportions in the United States, affecting about 25 million people of all ages and races, including about 7 million children; (2) Nearly one in 10 school-aged children has asthma, and the percentage of children with asthma is rising more rapidly in…

Facts about food irradiation: Irradiated foods and the consumer

International Nuclear Information System (INIS)

1991-01-01

This fact sheet discusses market testing of irradiate food, consumer response to irradiated products has always been positive, and in some countries commercial quantities of some irradiated food items have been sold on a regular basis. Consumers have shown no reluctance to buy irradiated food products. 4 refs

Analysis list: Stat5b [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Stat5b Blood,Breast + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Sta...t5b.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Stat5b.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/mm9/target/Stat5b.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Stat5b.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Stat5b.Breast.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Breast.gml ...

Optimal Materials and Deposition Technique Lead to Cost-Effective Solar Cell with Best-Ever Conversion Efficiency (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2012-07-01

This fact sheet describes how the SJ3 solar cell was invented, explains how the technology works, and why it won an R&D 100 Award. Based on NREL and Solar Junction technology, the commercial SJ3 concentrator solar cell - with 43.5% conversion efficiency at 418 suns - uses a lattice-matched multijunction architecture that has near-term potential for cells with {approx}50% efficiency. Multijunction solar cells have higher conversion efficiencies than any other type of solar cell. But developers of utility-scale and space applications crave even better efficiencies at lower costs to be both cost-effective and able to meet the demand for power. The SJ3 multijunction cell, developed by Solar Junction with assistance from foundational technological advances by the National Renewable Energy Laboratory, has the highest efficiency to date - almost 2% absolute more than the current industry standard multijunction cell-yet at a comparable cost. So what did it take to create this cell having 43.5% efficiency at 418-sun concentration? A combination of materials with carefully designed properties, a manufacturing technique allowing precise control, and an optimized device design.

Facts about food irradiation: Irradiation and food safety

International Nuclear Information System (INIS)

1991-01-01

This fact sheet focusses on the question of whether irradiation can be used to make spoiled food good. No food processing procedures can substitute for good hygienic practices, and good manufacturing practices must be followed in the preparation of food whether or not the food is intended for further processing by irradiation or any other means. 3 refs

HIV-1 Promotes the Degradation of Components of the Type 1 IFN JAK/STAT Pathway and Blocks Anti-viral ISG Induction.

Science.gov (United States)

Gargan, Siobhan; Ahmed, Suaad; Mahony, Rebecca; Bannan, Ciaran; Napoletano, Silvia; O'Farrelly, Cliona; Borrow, Persephone; Bergin, Colm; Stevenson, Nigel J

2018-04-01

Anti-retroviral therapy successfully suppresses HIV-1 infection, but fails to provide a cure. During infection Type 1 IFNs normally play an essential role in viral clearance, but in vivo IFN-α only has a modest impact on HIV-1 infection, suggesting its possible targeting by HIV. Here, we report that the HIV protein, Vif, inhibits effective IFN-α signalling via degradation of essential JAK/STAT pathway components. We found that STAT1 and STAT3 are specifically reduced in HEK293T cells expressing Vif and that full length, infectious HIV-1 IIIB strain promotes their degradation in a Vif-dependent manner. HIV-1 IIIB infection of myeloid ThP-1 cells also reduced the IFN-α-mediated induction of the anti-viral gene, ISG15, but not MxA, revealing a functional consequence of this HIV-1-mediated immune evasion strategy. Interestingly, while total STAT levels were not reduced upon in vitro IIIB infection of primary human PBMCs, IFN-α-mediated phosphorylation of STAT1 and STAT3 and ISG induction were starkly reduced, with removal of Vif (IIIBΔVif), partially restoring pSTATs, ISG15 and MxB induction. Similarly, pSTAT1 and pSTAT3 expression and IFN-α-induced ISG15 were reduced in PBMCs from HIV-infected patients, compared to healthy controls. Furthermore, IFN-α pre-treatment of a CEM T lymphoblast cells significantly inhibited HIV infection/replication (measured by cellular p24), only in the absence of Vif (IIIBΔVif), but was unable to suppress full length IIIB infection. When analysing the mechanism by which Vif might target the JAK/STAT pathway, we found Vif interacts with both STAT1 and STAT3, (but not STAT2), and its expression promotes ubiquitination and MG132-sensitive, proteosomal degradation of both proteins. Vif's Elongin-Cullin-SOCS-box binding motif enables the formation of an active E3 ligase complex, which we found to be required for Vif's degradation of STAT1 and STAT3. In fact, the E3 ligase scaffold proteins, Cul5 and Rbx2, were also found to be

Biologic consequences of Stat1-independent IFN signaling

OpenAIRE

Gil, M. Pilar; Bohn, Erwin; O'Guin, Andrew K.; Ramana, Chilakamarti V.; Levine, Beth; Stark, George R.; Virgin, Herbert W.; Schreiber, Robert D.

2001-01-01

Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNγ functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now demonstrate that both IFNγ and IFNα/β regulate proliferative responses in cells of the mononuclear phagocyte lineage derived from Stat1-null mice. Using both representational difference analysis and gene arrays, we show that IFNγ exerts its Stat1-independent actions on m...

STAT3 Target Genes Relevant to Human Cancers

International Nuclear Information System (INIS)

Carpenter, Richard L.; Lo, Hui-Wen

2014-01-01

Since its discovery, the STAT3 transcription factor has been extensively studied for its function as a transcriptional regulator and its role as a mediator of development, normal physiology, and pathology of many diseases, including cancers. These efforts have uncovered an array of genes that can be positively and negatively regulated by STAT3, alone and in cooperation with other transcription factors. Through regulating gene expression, STAT3 has been demonstrated to play a pivotal role in many cellular processes including oncogenesis, tumor growth and progression, and stemness. Interestingly, recent studies suggest that STAT3 may behave as a tumor suppressor by activating expression of genes known to inhibit tumorigenesis. Additional evidence suggested that STAT3 may elicit opposing effects depending on cellular context and tumor types. These mixed results signify the need for a deeper understanding of STAT3, including its upstream regulators, parallel transcription co-regulators, and downstream target genes. To help facilitate fulfilling this unmet need, this review will be primarily focused on STAT3 downstream target genes that have been validated to associate with tumorigenesis and/or malignant biology of human cancers

STAT3 activation in monocytes accelerates liver cancer progression

International Nuclear Information System (INIS)

Wu, Wen-Yong; Li, Jun; Wu, Zheng-Sheng; Zhang, Chang-Le; Meng, Xiang-Ling

2011-01-01

Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor ubiquitously expressed in different cell types. STAT3 plays an essential role in cell survival, proliferation, and differentiation. Aberrantly hyper-activated STAT3 signaling in cancer cells and in the tumor microenvironment has been detected in a wide variety of human cancers and is considered an important factor for cancer initiation, development, and progression. However, the role of STAT3 activation in monocytes in the development of HCC has not been well understood. Immunohistochemical analysis of phosphorylated STAT3 was performed on tissue microarray from HCC patients. Using a co-culture system in vivo, HCC cell growth was determined by the MTT assay. In vivo experiments were conducted with mice given diethylinitrosamine (DEN), which induces HCC was used to investigate the role of STAT3 expression in monocytes on tumor growth. Real-time PCR was used to determine the expression of cell proliferation and cell arrest associated genes in the tumor and nontumor tissue from liver. Phosphorylated STAT3 was found in human hepatocellular carcinoma tissue samples and was expressed in tumor cells and also in monocytes. Phosphorylated STAT3 expression in monocyte was significantly correlated to advanced clinical stage of HCC and a poor prognosis. Using a co-culture system in vivo, monocytes promoted HCC cell growth via the IL-6/STAT3 signaling pathway. The STAT3 inhibitor, NSC 74859, significantly suppressed tumor growth in vivo in mice with diethylinitrosamine (DEN)-induced HCC. In this animal model, blockade of STAT3 with NSC 74859 induced tumor cell apoptosis, while inhibiting both tumor cells and monocytes proliferation. Furthermore, NSC 74859 treatment suppressed cancer associated inflammation in DEN-induce HCC. Our data suggest constitutively activated STAT3 monocytes promote liver tumorigenesis in clinical patients and animal experiments. Thus, STAT3 in tumor

STAT6 expression in glioblastoma promotes invasive growth

International Nuclear Information System (INIS)

Merk, Barbara C; Owens, Jennifer L; Lopes, Maria-Beatriz S; Silva, Corinne M; Hussaini, Isa M

2011-01-01

Glioblastoma (GBM) is a highly aggressive malignant primary brain tumor, characterized by rapid growth, diffuse infiltration of cells into both adjacent and remote brain regions, and a generalized resistance to currently available treatment modalities. Recent reports in the literature suggest that Signal Transducers and Activators of Transcription (STATs) play important roles in the regulation of GBM pathophysiology. STAT6 protein expression was analyzed by Western blotting in GBM cell lines and by immunohistochemistry in a tissue microarray (TMA) of glioma patient tissues. We utilized shRNA against STAT6 to investigate the effects of prolonged STAT6 depletion on the growth and invasion of two STAT6-positive GBM cell lines. Cell proliferation was assessed by measuring 3 H-Thymidine uptake over time. Invasion was measured using an in vitro transwell assay in which cells invade through a type IV collagen matrix toward a chemoattractant (Fetal Bovine Serum). Cells were then stained and counted. Kaplan-Meyer survival curves were generated to show the correlation between STAT6 gene expression and patient survival in 343 glioma patients and in a subset of patients with only GBM. Gene expression microarray and clinical data were acquired from the Rembrandt [1] public data depository (https://caintegrator.nci.nih.gov/rembrandt/). Lastly, a genome-wide expression microarray analysis was performed to compare gene expression in wild-type GBM cells to expression in stable STAT6 knockdown clones. STAT6 was expressed in 2 GBM cell lines, U-1242MG and U-87MG, and in normal astrocytes (NHA) but not in the U-251MG GBM cell line. In our TMA study, STAT6 immunostaining was visible in the majority of astrocytomas of all grades (I-IV) but not in normal brain tissue. In positive cells, STAT6 was localized exclusively in the nuclei over 95% of the time. STAT6-deficient GBM cells showed a reduction in 3 H-Thymidine uptake compared to the wild-type. There was some variation among the

Acne Facts and Stats

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... neck. 17, 27 In females 15-29 years old, the torso/trunk is the most common location ... Publications Connect With Us Contact Us Media contacts Advertising contacts AAD logo Advertising, marketing and sponsorships Legal ...

CPR Facts and Stats

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... TRAINING Among 2,000 employees in corporate offices, hospitality, education and industry/labor: 55 percent can’t ... cannot locate an AED at work. In the hospitality industry, 66 percent of employees cannot locate an ...

CPR Facts and Stats

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... In Schools Training Kits RQI AHA Blended Learning & eLearning Guide AHA Instructors ECC Educational Conferences Programs CPR ... In Schools Training Kits RQI AHA Blended Learning & eLearning Guide AHA Instructors ECC Educational Conferences Programs CPR ...

Fact Sheets

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... PCE) PDF | Espanol PDF Pesticides PDF | Espanol PDF Pregnancy and Natural Disasters PDF | Espanol PDF Reproductive Hazards of the Workplace PDF | Espanol PDF Research Study Participation PDF | Espanol ...

Response of brain oxygenation and metabolism to deep hypothermic circulatory arrest in newborn piglets: comparison of pH-stat and alpha-stat strategies.

Science.gov (United States)

Markowitz, Scott D; Mendoza-Paredes, Alberto; Liu, Huiping; Pastuszko, Peter; Schultz, Steven P; Schears, Gregory J; Greeley, William J; Wilson, David F; Pastuszko, Anna

2007-07-01

To determine the effect of pH-stat as compared with alpha-stat management on brain oxygenation, level of striatal extracellular dopamine, phosphorylation, and levels of protein kinase B (Akt) and cyclic adenosine 3', 5'-monophosphate response element-binding protein (CREB), and levels of extracellular signal-regulated kinase (ERK)1/2, Bcl-2, and Bax in a piglet model of deep hypothermic circulatory arrest (DHCA). The piglets were placed on cardiopulmonary bypass (CPB), cooled with pH-stat or alpha-stat to 18 degrees C, subjected to 90 minutes of DHCA, rewarmed, weaned from CPB, and maintained for two hours recovery. The cortical oxygen was measured by: quenching of phosphorescence; dopamine by microdialysis; phosphorylation of CREB (p-CREB), ERK (p-ERK) 1/2, Akt (p-Akt), and level of Bcl-2, Bax by Western blots. Oxygen pressure histograms for the microvasculature of the cortex show substantially higher oxygen levels during cooling and during the oxygen depletion period after cardiac arrest (up to 15 minutes) when using pH-stat compared with alpha-stat management. Significant increases in dopamine occurred at 45 minutes and 60 minutes of DHCA in the alpha-stat and pH-stat groups, respectively. The p-CREB and p-Akt in the pH-stat group were significantly higher than in the alpha-stat group (140 +/- 9%, p model, prolongs "safe" time of DHCA and provides some brain protection against ischemic injury.

Bi-directional electrons in the near-Earth plasma sheet

Directory of Open Access Journals (Sweden)

K. Shiokawa

2003-07-01

Full Text Available We have studied the occurrence characteristics of bi-directional electron pitch angle anisotropy (enhanced flux in field-aligned directions, F^ /F|| > 1.5 at energies of 0.1–30 keV using plasma and magnetic field data from the AMPTE/IRM satellite in the near-Earth plasma sheet. The occurrence rate increases in the tailward direction from XGSM = - 9 RE to - 19 RE . The occurrence rate is also enhanced in the midnight sector, and furthermore, whenever the elevation angle of the magnetic field is large while the magnetic field intensity is small, B ~ 15 nT. From these facts, we conclude that the bi-directional electrons in the central plasma sheet are produced mainly in the vicinity of the neutral sheet and that the contribution from ionospheric electrons is minor. A high occurrence is also found after earthward high-speed ion flows, suggesting Fermi-type field-aligned electron acceleration in the neutral sheet. Occurrence characteristics of bi-directional electrons in the plasma sheet boundary layer are also discussed.Key words. Magnetospheric physics (magnetospheric configuration and dynamics; magnetotail; plasma sheet

Stats to go

CERN Document Server

Buglear, John

2000-01-01

'Stats to Go' is a user-friendly guide for hospitality, leisure and tourism students who need to learn statistics and statistical techniques. 'Stats to go' is an ideal companion to hospitality, leisure and tourism studies as the breadth of coverage supports all taught numerical aspects of these types of course. Examples from hospitality, leisure and tourism organizations: * licensed premises * fast food outlets * hotels * theme parks and their environments are used to illustrate key issues of the text. The area of quantitative methods is one which many students find unapproachable or daunting. With the use of a clear learning structure, and a user friendly, non-theoretical approach, Buglear has created a text which students and lecturers alike will find indispensable.

The JAK-STAT transcriptional regulator, STAT-5, activates the ATM DNA damage pathway to induce HPV 31 genome amplification upon epithelial differentiation.

Directory of Open Access Journals (Sweden)

Shiyuan Hong

Full Text Available High-risk human papillomavirus (HPV must evade innate immune surveillance to establish persistent infections and to amplify viral genomes upon differentiation. Members of the JAK-STAT family are important regulators of the innate immune response and HPV proteins downregulate expression of STAT-1 to allow for stable maintenance of viral episomes. STAT-5 is another member of this pathway that modulates the inflammatory response and plays an important role in controlling cell cycle progression in response to cytokines and growth factors. Our studies show that HPV E7 activates STAT-5 phosphorylation without altering total protein levels. Inhibition of STAT-5 phosphorylation by the drug pimozide abolishes viral genome amplification and late gene expression in differentiating keratinocytes. In contrast, treatment of undifferentiated cells that stably maintain episomes has no effect on viral replication. Knockdown studies show that the STAT-5β isoform is mainly responsible for this activity and that this is mediated through the ATM DNA damage response. A downstream target of STAT-5, the peroxisome proliferator-activated receptor γ (PPARγ contributes to the effects on members of the ATM pathway. Overall, these findings identify an important new regulatory mechanism by which the innate immune regulator, STAT-5, promotes HPV viral replication through activation of the ATM DNA damage response.

STAT proteins: from normal control of cellular events to tumorigenesis.

Science.gov (United States)

Calò, Valentina; Migliavacca, Manuela; Bazan, Viviana; Macaluso, Marcella; Buscemi, Maria; Gebbia, Nicola; Russo, Antonio

2003-11-01

Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors latent in the cytoplasm that participate in normal cellular events, such as differentiation, proliferation, cell survival, apoptosis, and angiogenesis following cytokine, growth factor, and hormone signaling. STATs are activated by tyrosine phosphorylation, which is normally a transient and tightly regulates process. Nevertheless, several constitutively activated STATs have been observed in a wide number of human cancer cell lines and primary tumors, including blood malignancies and solid neoplasias. STATs can be divided into two groups according to their specific functions. One is made up of STAT2, STAT4, and STAT6, which are activated by a small number of cytokines and play a distinct role in the development of T-cells and in IFNgamma signaling. The other group includes STAT1, STAT3, and STAT5, activated in different tissues by means of a series of ligands and involved in IFN signaling, development of the mammary gland, response to GH, and embriogenesis. This latter group of STATS plays an important role in controlling cell-cycle progression and apoptosis and thus contributes to oncogenesis. Although an increased expression of STAT1 has been observed in many human neoplasias, this molecule can be considered a potential tumor suppressor, since it plays an important role in growth arrest and in promoting apoptosis. On the other hand, STAT3 and 5 are considered as oncogenes, since they bring about the activation of cyclin D1, c-Myc, and bcl-xl expression, and are involved in promoting cell-cycle progression, cellular transformation, and in preventing apoptosis.

Numerical and experimental analysis of resistance projection welding of square nuts to sheets

DEFF Research Database (Denmark)

Nielsen, Chris Valentin; Zhang, Wenqi; Martins, Paulo A.F.

2014-01-01

Projection welding of nuts to sheets is a widely utilized manufacturing process in the automotive industry. The process entails challenges due the necessity of joining different sheet thicknesses and nut sizes made from dissimilar materials, and due to the fact of experiencing large local deforma...... of the square nut to the sheet under different operating conditions. © 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license...

STAT6 expression in glioblastoma promotes invasive growth

Directory of Open Access Journals (Sweden)

Silva Corinne M

2011-05-01

Full Text Available Abstract Background Glioblastoma (GBM is a highly aggressive malignant primary brain tumor, characterized by rapid growth, diffuse infiltration of cells into both adjacent and remote brain regions, and a generalized resistance to currently available treatment modalities. Recent reports in the literature suggest that Signal Transducers and Activators of Transcription (STATs play important roles in the regulation of GBM pathophysiology. Methods STAT6 protein expression was analyzed by Western blotting in GBM cell lines and by immunohistochemistry in a tissue microarray (TMA of glioma patient tissues. We utilized shRNA against STAT6 to investigate the effects of prolonged STAT6 depletion on the growth and invasion of two STAT6-positive GBM cell lines. Cell proliferation was assessed by measuring 3H-Thymidine uptake over time. Invasion was measured using an in vitro transwell assay in which cells invade through a type IV collagen matrix toward a chemoattractant (Fetal Bovine Serum. Cells were then stained and counted. Kaplan-Meyer survival curves were generated to show the correlation between STAT6 gene expression and patient survival in 343 glioma patients and in a subset of patients with only GBM. Gene expression microarray and clinical data were acquired from the Rembrandt 1 public data depository (https://caintegrator.nci.nih.gov/rembrandt/. Lastly, a genome-wide expression microarray analysis was performed to compare gene expression in wild-type GBM cells to expression in stable STAT6 knockdown clones. Results STAT6 was expressed in 2 GBM cell lines, U-1242MG and U-87MG, and in normal astrocytes (NHA but not in the U-251MG GBM cell line. In our TMA study, STAT6 immunostaining was visible in the majority of astrocytomas of all grades (I-IV but not in normal brain tissue. In positive cells, STAT6 was localized exclusively in the nuclei over 95% of the time. STAT6-deficient GBM cells showed a reduction in 3H-Thymidine uptake compared to the wild

The Inflammatory Transcription Factors NFκB, STAT1 and STAT3 Drive Age-Associated Transcriptional Changes in the Human Kidney

Science.gov (United States)

O’Brown, Zach K.; Van Nostrand, Eric L.; Higgins, John P.; Kim, Stuart K.

2015-01-01

Human kidney function declines with age, accompanied by stereotyped changes in gene expression and histopathology, but the mechanisms underlying these changes are largely unknown. To identify potential regulators of kidney aging, we compared age-associated transcriptional changes in the human kidney with genome-wide maps of transcription factor occupancy from ChIP-seq datasets in human cells. The strongest candidates were the inflammation-associated transcription factors NFκB, STAT1 and STAT3, the activities of which increase with age in epithelial compartments of the renal cortex. Stimulation of renal tubular epithelial cells with the inflammatory cytokines IL-6 (a STAT3 activator), IFNγ (a STAT1 activator), or TNFα (an NFκB activator) recapitulated age-associated gene expression changes. We show that common DNA variants in RELA and NFKB1, the two genes encoding subunits of the NFκB transcription factor, associate with kidney function and chronic kidney disease in gene association studies, providing the first evidence that genetic variation in NFκB contributes to renal aging phenotypes. Our results suggest that NFκB, STAT1 and STAT3 underlie transcriptional changes and chronic inflammation in the aging human kidney. PMID:26678048

Associations between STAT Gene Polymorphisms and Psoriasis in Northeastern China.

Science.gov (United States)

Zhou, Jing; Li, Yuzhen; Sun, Donglin

2017-01-01

Psoriasis is an autoimmune disease with genetic and environmental factors. Based on the roles of STATs (signaling transducers and activators of transcription) in autoimmune diseases, it is assumed STAT gene polymorphisms are associated with psoriasis. To study the association between STAT gene polymorphisms and psoriasis in the northeastern Chinese population. Eight single-nucleotide polymorphisms were genotyped: rs2293152, rs3816769, rs4796793, and rs744166 in STAT3, rs7574865 and rs3024866 in STAT4, and rs324011 and rs3024974 in STAT6, using SNaPshot methods. The genotype, allele, and haplotype frequencies were compared between 400 psoriasis patients and 398 healthy individuals in northeastern China. rs744166GG in STAT3 and rs7574865TT in STAT4 had higher frequencies in the case than the control group, suggesting these 2 genotypes increase the susceptibility to psoriasis (p < 0.05). Three haplotypes (H3, H6, and H7) were found to be associated with psoriasis in the study (p < 0.05). These results indicate a role of STAT genes in the pathogenesis of psoriasis. © 2017 S. Karger AG, Basel.

Roles of STATs signaling in cardiovascular diseases.

Science.gov (United States)

Kishore, Raj; Verma, Suresh K

2012-04-01

In cardiac and many other systems, chronic stress activates avfamily of structurally and functionally conserved receptors and their downstream signaling molecules that entail tyrosine, serine or threonine phosphorylation to transfer the messages to the genetic machinery. However, the activation of the Janus kinases (JAKs) and their downstream signal transducer and activator of transcription (STATs) proteins is both characteristic of and unique to cytokine and growth factor signaling which plays a central role in heart physiology. Dysregulation of JAK-STAT signaling is associated with various cardiovascular diseases. The molecular signaling and specificity of the JAK-STAT pathway are modulated at many levels by distinct regulatory proteins. Here, we review recent studies on the regulation of the STAT signaling pathway that will enhance our ability to design rational therapeutic strategies for stress-induced heart failure.

Facts about food irradiation: Safety of irradiation facilities

International Nuclear Information System (INIS)

1991-01-01

This fact sheet considers the safety of industrial irradiation facilities. Although there have been accidents, none of them has endangered public health or environmental safety, and the radiation processing industry is considered to have a very good safety record. Gamma irradiators do not produce radioactive waste, and the radiation sources at the facilities cannot explode nor in any other way release radioactivity into the environment. 3 refs

Ice sheet hydrology - a review

International Nuclear Information System (INIS)

Jansson, Peter; Naeslund, Jens-Ove; Rodhe, Lars

2007-03-01

This report summarizes the theoretical knowledge on water flow in and beneath glaciers and ice sheets and how these theories are applied in models to simulate the hydrology of ice sheets. The purpose is to present the state of knowledge and, perhaps more importantly, identify the gaps in our understanding of ice sheet hydrology. Many general concepts in hydrology and hydraulics are applicable to water flow in glaciers. However, the unique situation of having the liquid phase flowing in conduits of the solid phase of the same material, water, is not a commonly occurring phenomena. This situation means that the heat exchange between the phases and the resulting phase changes also have to be accounted for in the analysis. The fact that the solidus in the pressure-temperature dependent phase diagram of water has a negative slope provides further complications. Ice can thus melt or freeze from both temperature and pressure variations or variations in both. In order to provide details of the current understanding of water flow in conjunction with deforming ice and to provide understanding for the development of ideas and models, emphasis has been put on the mathematical treatments, which are reproduced in detail. Qualitative results corroborating theory or, perhaps more often, questioning the simplifications made in theory, are also given. The overarching problem with our knowledge of glacier hydrology is the gap between the local theories of processes and the general flow of water in glaciers and ice sheets. Water is often channelized in non-stationary conduits through the ice, features which due to their minute size relative to the size of glaciers and ice sheets are difficult to incorporate in spatially larger models. Since the dynamic response of ice sheets to global warming is becoming a key issue in, e.g. sea-level change studies, the problems of the coupling between the hydrology of an ice sheet and its dynamics is steadily gaining interest. New work is emerging

Ice sheet hydrology - a review

Energy Technology Data Exchange (ETDEWEB)

Jansson, Peter; Naeslund, Jens-Ove [Dept. of Physical Geography and Quaternary Geology, Stockholm Univ., Stockholm (Sweden); Rodhe, Lars [Geological Survey of Sweden, Uppsala (Sweden)

2007-03-15

This report summarizes the theoretical knowledge on water flow in and beneath glaciers and ice sheets and how these theories are applied in models to simulate the hydrology of ice sheets. The purpose is to present the state of knowledge and, perhaps more importantly, identify the gaps in our understanding of ice sheet hydrology. Many general concepts in hydrology and hydraulics are applicable to water flow in glaciers. However, the unique situation of having the liquid phase flowing in conduits of the solid phase of the same material, water, is not a commonly occurring phenomena. This situation means that the heat exchange between the phases and the resulting phase changes also have to be accounted for in the analysis. The fact that the solidus in the pressure-temperature dependent phase diagram of water has a negative slope provides further complications. Ice can thus melt or freeze from both temperature and pressure variations or variations in both. In order to provide details of the current understanding of water flow in conjunction with deforming ice and to provide understanding for the development of ideas and models, emphasis has been put on the mathematical treatments, which are reproduced in detail. Qualitative results corroborating theory or, perhaps more often, questioning the simplifications made in theory, are also given. The overarching problem with our knowledge of glacier hydrology is the gap between the local theories of processes and the general flow of water in glaciers and ice sheets. Water is often channelized in non-stationary conduits through the ice, features which due to their minute size relative to the size of glaciers and ice sheets are difficult to incorporate in spatially larger models. Since the dynamic response of ice sheets to global warming is becoming a key issue in, e.g. sea-level change studies, the problems of the coupling between the hydrology of an ice sheet and its dynamics is steadily gaining interest. New work is emerging

Passive Reactor Compensated Cascaded H-Bridge Multilevel LC-StatCom

DEFF Research Database (Denmark)

Farivar, Glen; Townsend, Christopher David; Hredzak, Branislav

2017-01-01

The cascaded H-bridge (CHB) low-capacitance StatCom (LC-StatCom) has a limited operating area in the inductive region compared to a conventional StatCom's V–I characteristic. This limitation for operation in the inductive region is considered to be the biggest disadvantage of CHB LC-StatCom. In t...

Propulsion Study for Small Transport Aircraft Technology (STAT)

Science.gov (United States)

Gill, J. C.; Earle, R. V.; Staton, D. V.; Stolp, P. C.; Huelster, D. S.; Zolezzi, B. A.

1980-01-01

Propulsion requirements were determined for 0.5 and 0.7 Mach aircraft. Sensitivity studies were conducted on both these aircraft to determine parametrically the influence of propulsion characteristics on aircraft size and direct operating cost (DOC). Candidate technology elements and design features were identified and parametric studies conducted to select the STAT advanced engine cycle. Trade off studies were conducted to determine those advanced technologies and design features that would offer a reduction in DOC for operation of the STAT engines. These features were incorporated in the two STAT engines. A benefit assessment was conducted comparing the STAT engines to current technology engines of the same power and to 1985 derivatives of the current technology engines. Research and development programs were recommended as part of an overall technology development plan to ensure that full commercial development of the STAT engines could be initiated in 1988.

STAT3 Activation in Glioblastoma: Biochemical and Therapeutic Implications

Energy Technology Data Exchange (ETDEWEB)

Kim, Jennifer E.; Patel, Mira; Ruzevick, Jacob; Jackson, Christopher M.; Lim, Michael, E-mail: mlim3@jhmi.edu [Department of Neurosurgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe St., Phipps Building Rm 123, Baltimore, MD 21287 (United States)

2014-02-10

Signal transducer and activator of transcription 3 (STAT3) is a potent regulator of gliomagenesis through its induction of angiogenesis, host immunosuppression, and tumor invasion. Gain of function mutations result in constitutive activation of STAT3 in glioma cells, making STAT3 an attractive target for inhibition in cancer therapy. Nevertheless, some studies show that STAT3 also participates in terminal differentiation and apoptosis of various cell lines and in glioma with phosphatase and tensin homolog (PTEN)-deficient genetic backgrounds. In light of these findings, the utility of STAT3 as a prognostic indicator and as a target of drug therapies will be contingent on a more nuanced understanding of its pro- and anti-tumorigenic effects.

Facts about food irradiation: Genetic studies

International Nuclear Information System (INIS)

1991-01-01

Results published in the mid-1970s from the National Institute of Nutrition (NIN) in India showed increased numbers of polyploid cells in rats, mice, monkeys and malnourished children fed irradiated wheat products. This fact sheet considers the validity of these results. A large number of independent studies have been subsequently performed, and in none of these have results been obtained that support the NIN findings. The conclusion is that there is no evidence to link the consumption of irradiated food with any mutagenic effect. 3 refs

Meningeal hemangiopericytoma and solitary fibrous tumors carry the NAB2-STAT6 fusion and can be diagnosed by nuclear expression of STAT6 protein.

Science.gov (United States)

Schweizer, Leonille; Koelsche, Christian; Sahm, Felix; Piro, Rosario M; Capper, David; Reuss, David E; Pusch, Stefan; Habel, Antje; Meyer, Jochen; Göck, Tanja; Jones, David T W; Mawrin, Christian; Schittenhelm, Jens; Becker, Albert; Heim, Stephanie; Simon, Matthias; Herold-Mende, Christel; Mechtersheimer, Gunhild; Paulus, Werner; König, Rainer; Wiestler, Otmar D; Pfister, Stefan M; von Deimling, Andreas

2013-05-01

Non-central nervous system hemangiopericytoma (HPC) and solitary fibrous tumor (SFT) are considered by pathologists as two variants of a single tumor entity now subsumed under the entity SFT. Recent detection of frequent NAB2-STAT6 fusions in both, HPC and SFT, provided additional support for this view. On the other hand, current neuropathological practice still distinguishes between HPC and SFT. The present study set out to identify genes involved in the formation of meningeal HPC. We performed exome sequencing and detected the NAB2-STAT6 fusion in DNA of 8/10 meningeal HPC thereby providing evidence of close relationship of these tumors with peripheral SFT. Due to the considerable effort required for exome sequencing, we sought to explore surrogate markers for the NAB2-STAT6 fusion protein. We adopted the Duolink proximity ligation assay and demonstrated the presence of NAB2-STAT6 fusion protein in 17/17 HPC and the absence in 15/15 meningiomas. More practical, presence of the NAB2-STAT6 fusion protein resulted in a strong nuclear signal in STAT6 immunohistochemistry. The nuclear reallocation of STAT6 was detected in 35/37 meningeal HPC and 25/25 meningeal SFT but not in 87 meningiomas representing the most important differential diagnosis. Tissues not harboring the NAB2-STAT6 fusion protein presented with nuclear expression of NAB2 and cytoplasmic expression of STAT6 proteins. In conclusion, we provide strong evidence for meningeal HPC and SFT to constitute variants of a single entity which is defined by NAB2-STAT6 fusion. In addition, we demonstrate that this fusion can be rapidly detected by STAT6 immunohistochemistry which shows a consistent nuclear reallocation. This immunohistochemical assay may prove valuable for the differentiation of HPC and SFT from other mesenchymal neoplasms.

'Papillary' solitary fibrous tumor/hemangiopericytoma with nuclear STAT6 expression and NAB2-STAT6 fusion.

Science.gov (United States)

Ishizawa, Keisuke; Tsukamoto, Yoshitane; Ikeda, Shunsuke; Suzuki, Tomonari; Homma, Taku; Mishima, Kazuhiko; Nishikawa, Ryo; Sasaki, Atsushi

2016-04-01

This report describes clinicopathological findings, including genetic data of STAT6, in a solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) of the central nervous system in an 83-year-old woman with a bulge in the left forehead. She noticed it about 5 months before, and it had grown rapidly for the past 1 month. Neuroradiological studies disclosed a well-demarcated tumor that accompanied the destruction of the skull. The excised tumor showed a prominent papillary structure, where atypical cells were compactly arranged along the fibrovascular core ('pseudopapillary'). There was rich vasculature, some of which resembled 'staghorn' vessels. Mitotic figures were occasionally found. Whorls, psammoma bodies, or intra-nuclear pseudoinclusions were not identified. By immunohistochemistry, CD34 was strongly positive in the tumor cells, and STAT6 was localized in their nuclei. By reverse transcription-polymerase chain reaction (RT-PCR), an NAB2-STAT6 fusion gene, NAB2 exon6-STAT6 exon17, was detected, establishing a definite diagnosis of SFT/HPC. 'Papillary' SFT/HPC needs to be recognized as a possible morphological variant of SFT/HPC, and should be borne in mind in its diagnostic practice.

Overcoming Chemoresistance of Pediatric Ependymoma by Inhibition of STAT3 Signaling

Directory of Open Access Journals (Sweden)

Ji Hoon Phi

2015-10-01

Full Text Available The long-term clinical outcome of pediatric intracranial epepdymoma is poor with a high rate of recurrence. One of the main reasons for this poor outcome is the tumor’s inherent resistance to chemotherapy. Signal transducer and activator of transcription 3 (STAT3 is overactive in many human cancers, and inhibition of STAT3 signaling is an emerging area of interest in oncology. In this study, the possibility of STAT3 inhibition as a treatment was investigated in pediatric intracranial ependymoma tissues and cell lines. STAT3 activation status was checked in ependymoma tissues. The responses to conventional chemotherapeutic agents and a STAT3 inhibitor WP1066 in primarily cultured ependymoma cells were measured by cell viability assay. Apoptosis assays were conducted to reveal the cytotoxic mechanism of applied agents. Knockdown of STAT3 was tried to confirm the effects of STAT3 inhibition in ependymoma cells. High levels of phospho-STAT3 (p-STAT3 expression were observed in ependymoma tissue, especially in the anaplastic histology group. There was no cytotoxic effect of cisplatin, ifosfamide, and etoposide. Both brain tumor-initiating cells (BTICs and bulk tumor cells (BCs showed considerably decreased viability after WP1066 treatment. However, BTICs had fewer responses than BCs. No additive or synergistic effect was observed for combination therapy of WP1066 and cisplatin. WP1066 effectively abrogated p-STAT3 expression. An increased apoptosis and decreased Survivin expression were observed after WP1066 treatment. Knockdown of STAT3 also decreased cell survival, supporting the critical role of STAT3 in sustaining ependymoma cells. In this study, we observed a cytotoxic effect of STAT3 inhibitor on ependymoma BTICs and BCs. There is urgent need to develop new therapeutic agents for pediatric ependymoma. STAT3 inhibitors may be a new group of drugs for clinical application.

Human Cytomegalovirus Immediate-Early 1 Protein Rewires Upstream STAT3 to Downstream STAT1 Signaling Switching an IL6-Type to an IFNγ-Like Response.

Directory of Open Access Journals (Sweden)

Thomas Harwardt

2016-07-01

Full Text Available The human cytomegalovirus (hCMV major immediate-early 1 protein (IE1 is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445 in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420 deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.

STAT3: An Anti-Invasive Factor in Colorectal Cancer?

Energy Technology Data Exchange (ETDEWEB)

Jong, Petrus Rudolf de [Department of Medicine, University of California, San Diego, 9500 Gilman Dr. MC 0663, La Jolla, CA 92093 (United States); Mo, Ji-Hun [Department of Otorhinolaryngology, Dankook University College of Medicine, 16-5 Anseo-dong, Cheonan, Chungcheongnam-do 330-715 (Korea, Republic of); Harris, Alexandra R.; Lee, Jongdae, E-mail: j142lee@ucsd.edu; Raz, Eyal [Department of Medicine, University of California, San Diego, 9500 Gilman Dr. MC 0663, La Jolla, CA 92093 (United States)

2014-07-03

Signal Transducer and Activator of Transcription 3 (STAT3) is activated in a majority of cancers, and promotes tumorigenesis and even metastasis through transcriptional activation of its target genes. Recently, we discovered that STAT3 suppresses epithelial-to-mesenchymal transition (EMT) and thus metastasis in a mouse model of colorectal cancer (CRC), while it did not affect the overall tumor burden. Furthermore, we found that STAT3 in intestinal epithelial cells (IEC) suppresses EMT by regulating stability of an EMT inducer, SNAI-1 (Snail-1). Here, STAT3 functions as an adaptor rather than a transcription factor in the post-translational modification of SNAI-1. In this review, we discuss the unexpected and contradictory role of STAT3 in metastasis of CRC and its clinical implications.

STAT4 gene polymorphism in patients after renal allograft transplantation.

Science.gov (United States)

Dąbrowska-Żamojcin, Ewa; Dziedziejko, Violetta; Safranow, Krzysztof; Domański, Leszek; Słuczanowska-Głabowska, Sylwia; Pawlik, Andrzej

2016-01-01

STAT4 (signal transducer and activator of transcription 4) is involved in the regulation of innate and adaptive immune responses. Some studies have suggested that STAT4 may be involved in the immune response after graft transplantation. Several polymorphisms in the STAT4 gene have been identified. The most commonly studied polymorphism in the STAT4 gene is rs7574865. In our study, we examined whether this polymorphism is associated with the early and late functions of renal allografts. A total of 270 recipients of first renal transplants were included in the study. Single nucleotide polymorphisms (SNPs) within the STAT4 gene were genotyped using TaqMan genotyping assays. There were no statistically significant associations between the STAT4 gene rs7574865 polymorphism and delayed graft function, acute rejection, chronic allograft dysfunction, post-transplant diabetes mellitus, or creatinine serum concentrations after transplantation. Our results suggest a lack of association between the STAT4 rs7574865 SNP and kidney allograft function in the Polish population.

FastStats: Measles

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... Women’s Health State and Territorial Data Reproductive Health Contraceptive Use Infertility Reproductive Health Notice Regarding FastStats Mobile ... measles, mumps, rubella: 91.9% (2015) Percent of adolescents aged 13-17 years vaccinated against measles, mumps, ...

FastStats: Immunization

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... Women’s Health State and Territorial Data Reproductive Health Contraceptive Use Infertility Reproductive Health Notice Regarding FastStats Mobile ... 69 [PDF – 9.8 MB] Vaccination coverage among adolescents 13-17 years of age Health, United States, ...

Morbillivirus control of the interferon response: relevance of STAT2 and mda5 but not STAT1 for canine distemper virus virulence in ferrets.

Science.gov (United States)

Svitek, Nicholas; Gerhauser, Ingo; Goncalves, Christophe; Grabski, Elena; Döring, Marius; Kalinke, Ulrich; Anderson, Danielle E; Cattaneo, Roberto; von Messling, Veronika

2014-03-01

The V proteins of paramyxoviruses control the innate immune response. In particular, the V protein of the genus Morbillivirus interferes with the signal transducer and activator of transcription 1 (STAT1), STAT2, and melanoma differentiation-associated protein 5 (mda5) signaling pathways. To characterize the contributions of these pathways to canine distemper virus (CDV) pathogenesis, we took advantage of the knowledge about the mechanisms of interaction between the measles virus V protein with these key regulators of innate immunity. We generated recombinant CDVs with V proteins unable to properly interact with STAT1, STAT2, or mda5. A virus with combined STAT2 and mda5 deficiencies was also generated, and available wild-type and V-protein-knockout viruses were used as controls. Ferrets infected with wild-type and STAT1-blind viruses developed severe leukopenia and loss of lymphocyte proliferation activity and succumbed to the disease within 14 days. In contrast, animals infected with viruses with STAT2 or mda5 defect or both STAT2 and mda5 defects developed a mild self-limiting disease similar to that associated with the V-knockout virus. This study demonstrates the importance of interference with STAT2 and mda5 signaling for CDV immune evasion and provides a starting point for the development of morbillivirus vectors with reduced immunosuppressive properties. The V proteins of paramyxoviruses interfere with the recognition of the virus by the immune system of the host. For morbilliviruses, the V protein is known to interact with the signal transducer and activator of transcription 1 (STAT1) and STAT2 and the melanoma differentiation-associated protein 5 (mda5), which are involved in interferon signaling. Here, we examined the contribution of each of these signaling pathways to the pathogenesis of the carnivore morbillivirus canine distemper virus. Using viruses selectively unable to interfere with the respective signaling pathway to infect ferrets, we found that

STAT3: An Anti-Invasive Factor in Colorectal Cancer?

Directory of Open Access Journals (Sweden)

Petrus Rudolf de Jong

2014-07-01

Full Text Available Signal Transducer and Activator of Transcription 3 (STAT3 is activated in a majority of cancers, and promotes tumorigenesis and even metastasis through transcriptional activation of its target genes. Recently, we discovered that STAT3 suppresses epithelial-to-mesenchymal transition (EMT and thus metastasis in a mouse model of colorectal cancer (CRC, while it did not affect the overall tumor burden. Furthermore, we found that STAT3 in intestinal epithelial cells (IEC suppresses EMT by regulating stability of an EMT inducer, SNAI-1 (Snail-1. Here, STAT3 functions as an adaptor rather than a transcription factor in the post-translational modification of SNAI-1. In this review, we discuss the unexpected and contradictory role of STAT3 in metastasis of CRC and its clinical implications.

Role of Stat in Skin Carcinogenesis: Insights Gained from Relevant Mouse Models

International Nuclear Information System (INIS)

Macias, E.; Rao, D.; DiGiovanni, J.; DiGiovanni, J.; DiGiovanni, J.

2013-01-01

Signal transducer and activator of transcription 3 (Stat) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat-deficient mice have revealed that Stat plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat-deficient mouse models has demonstrated that Stat is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat in skin tumor progression. Studies using similar Stat-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat is an attractive target for skin cancer prevention and treatment.

Stat3 is involved in control of MASP2 gene expression

International Nuclear Information System (INIS)

Unterberger, Claudia; Hanson, Steven; Klingenhoff, Andreas; Oesterle, Daniela; Frankenberger, Marion; Endo, Yuichi; Matsushita, Misao; Fujita, Teizo; Schwaeble, Wilhelm; Weiss, Elisabeth H.; Ziegler-Heitbrock, Loems; Stover, Cordula

2007-01-01

Little is known about determinants regulating expression of Mannan-binding lectin associated serine protease-2 (MASP-2), the effector component of the lectin pathway of complement activation. Comparative bioinformatic analysis of the MASP2 promoter regions in human, mouse, and rat, revealed conservation of two putative Stat binding sites, termed StatA and StatB. Site directed mutagenesis specific for these sites was performed. Transcription activity was decreased 5-fold when StatB site was mutated in the wildtype reporter gene construct. Gel retardation and competition assays demonstrated that proteins contained in the nuclear extract prepared from HepG2 specifically bound double-stranded StatB oligonucleotides. Supershift analysis revealed Stat3 to be the major specific binding protein. We conclude that Stat3 binding is important for MASP2 promoter activity

Transcription Factor STAT3 as a Novel Molecular Target for Cancer Prevention

International Nuclear Information System (INIS)

Xiong, Ailian; Yang, Zhengduo; Shen, Yicheng; Zhou, Jia; Shen, Qiang

2014-01-01

Signal Transducers and Activators of Transcription (STATs) are a family of transcription factors that regulate cell proliferation, differentiation, apoptosis, immune and inflammatory responses, and angiogenesis. Cumulative evidence has established that STAT3 has a critical role in the development of multiple cancer types. Because it is constitutively activated during disease progression and metastasis in a variety of cancers, STAT3 has promise as a drug target for cancer therapeutics. Recently, STAT3 was found to have an important role in maintaining cancer stem cells in vitro and in mouse tumor models, suggesting STAT3 is integrally involved in tumor initiation, progression and maintenance. STAT3 has been traditionally considered as nontargetable or undruggable, and the lag in developing effective STAT3 inhibitors contributes to the current lack of FDA-approved STAT3 inhibitors. Recent advances in cancer biology and drug discovery efforts have shed light on targeting STAT3 globally and/or specifically for cancer therapy. In this review, we summarize current literature and discuss the potential importance of STAT3 as a novel target for cancer prevention and of STAT3 inhibitors as effective chemopreventive agents

Nuclear protein IκB-ζ inhibits the activity of STAT3

International Nuclear Information System (INIS)

Wu, Zhihao; Zhang, Xiaoai; Yang, Juntao; Wu, Guangzhou; Zhang, Ying; Yuan, Yanzhi; Jin, Chaozhi; Chang, Zhijie; Wang, Jian; Yang, Xiaoming; He, Fuchu

2009-01-01

STAT3 (Signal transducer and activator of transcription 3) is a key transcription factor of the JAK-STAT (Janus kinase/signal transducer and activator of transcription) pathway that regulates cell proliferation and apoptosis. Activation of STAT3 is under tight regulation, and yet the different signaling pathways and the mechanisms that regulate its activity remain to be elucidated. Using a yeast two-hybrid screening, we have identified a nuclear protein IκB-ζ that interacts in a novel way with STAT3. This physical interaction was further confirmed by co-immunoprecipitation assays. The interaction regions were mapped to the coiled-coil domain of STAT3 and the C-terminal of IκB-ζ. Overexpression of IκB-ζ inhibited the transcriptional activity of STAT3. It also suppressed cell growth and induced cell apoptosis in SRC-simulated cells, which is partially mediated by down-regulation of expression of a known STAT3 target gene, MCL1. Our results suggest that IκB-ζ is a negative regulator of STAT3, and demonstrate a novel mechanism in which a component of the NF-κB signaling pathway inhibits the activation of STAT3.

Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription

Science.gov (United States)

Vidal, Marcos; Ramana, Chilakamarti V.; Dusso, Adriana S.

2002-01-01

The cytokine gamma interferon (IFN-γ) and the calcitropic steroid hormone 1,25-dihydroxyvitamin D (1,25D) are activators of macrophage immune function. In sarcoidosis, tuberculosis, and several granulomatoses, IFN-γ induces 1,25D synthesis by macrophages and inhibits 1,25D induction of 24-hydroxylase, a key enzyme in 1,25D inactivation, causing high levels of 1,25D in serum and hypercalcemia. This study delineates IFN-γ-1,25D cross talk in human monocytes-macrophages. Nuclear accumulation of Stat1 and vitamin D receptor (VDR) by IFN-γ and 1,25D promotes protein-protein interactions between Stat1 and the DNA binding domain of the VDR. This prevents VDR-retinoid X receptor (RXR) binding to the vitamin D-responsive element, thus diverting the VDR from its normal genomic target on the 24-hydroxylase promoter and antagonizing 1,25D-VDR transactivation of this gene. In contrast, 1,25D enhances IFN-γ action. Stat1-VDR interactions, by preventing Stat1 deactivation by tyrosine dephosphorylation, cooperate with IFN-γ/Stat1-induced transcription. This novel 1,25D-IFN-γ cross talk explains the pathogenesis of abnormal 1,25D homeostasis in granulomatous processes and provides new insights into 1,25D immunomodulatory properties. PMID:11909970

Structural and functional studies of STAT1 from Atlantic salmon (Salmo salar

Directory of Open Access Journals (Sweden)

Thim Hanna L

2010-03-01

Full Text Available Abstract Background Type I and type II interferons (IFNs exert their effects mainly through the JAK/STAT pathway, which is presently best described in mammals. STAT1 is involved in signaling pathways induced by both types of IFNs. It has a domain-like structure including an amino-terminus that stabilizes interaction between STAT dimers in a promoter-binding situation, a coiled coil domain facilitating interactions to other proteins, a central DNA-binding domain, a SH2 domain responsible for dimerization of phosphorylated STATs and conserved phosphorylation sites within the carboxy terminus. The latter is also the transcriptional activation domain. Results A salmon (Salmo salar STAT1 homologue, named ssSTAT1a, has been identified and was shown to be ubiquitously expressed in various cells and tissues. The ssSTAT1a had a domain-like structure with functional motifs that are similar to higher vertebrates. Endogenous STAT1 was shown to be phosphorylated at tyrosine residues both in salmon leukocytes and in TO cells treated with recombinant type I and type II IFNs. Also ectopically expressed ssSTAT1 was phosphorylated in salmon cells upon in vitro stimulation by the IFNs, confirming that the cloned gene was recognized by upstream tyrosine kinases. Treatment with IFNs led to nuclear translocation of STAT1 within one hour. The ability of salmon STAT1 to dimerize was also shown. Conclusions The structural and functional properties of salmon STAT1 resemble the properties of mammalian STAT1.

SEER*Stat Software

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If you have access to SEER Research Data, use SEER*Stat to analyze SEER and other cancer-related databases. View individual records and produce statistics including incidence, mortality, survival, prevalence, and multiple primary. Tutorials and related analytic software tools are available.

Facts about food irradiation: Microbiological safety of irradiated food

International Nuclear Information System (INIS)

1991-01-01

This fact sheet considers the microbiological safety of irradiated food, with especial reference to Clostridium botulinum. Irradiated food, as food treated by any ''sub-sterilizing'' process, must be handled, packaged and stored following good manufacturing practices to prevent growth and toxin production of C. botulinum. Food irradiation does not lead to increased microbiological hazards, nor can it be used to save already spoiled foods. 4 refs

Constitutive STAT3-activation in Sezary syndrome: tyrphostin AG490 inhibits STAT3-activation, interleukin-2 receptor expression and growth of leukemic Sezary cells

DEFF Research Database (Denmark)

Eriksen, K W; Kaltoft, K; Mikkelsen, G

2001-01-01

are IL-2Ralpha negative. An aberrant expression of IL-2Ralpha has recently been described in cutaneous T-cell lymphoma (CTCL). Here, we study the regulation of IL-2Ralpha expression and STATs in a tumor cell line obtained from peripheral blood from a patient with Sezary syndrome (SS), a leukemic variant...... of CTCL. We show that (1) STAT3 (a transcription factor known to regulate IL-2Ralpha transcription) is constitutively tyrosine-phosphorylated in SS tumor cells, but not in non-malignant T cells; (2) STAT3 binds constitutively to a STAT-binding sequence in the promotor of the IL-2Ralpha gene; (3) the Janus...... kinase inhibitor, tyrphostine AG490, inhibits STAT3 activation, STAT3 DNA binding, and IL-2Ralpha mRNA and protein expression in parallel; and (4) tyrphostine AG490 inhibits IL-2 driven mitogenesis and triggers apoptosis in SS tumor cells. In conclusion, we provide the first example of a constitutive...

Stat1-independent regulation of gene expression in response to IFN-γ

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Ramana, Chilakamarti V.; Gil, M. Pilar; Han, Yulong; Ransohoff, Richard M.; Schreiber, Robert D.; Stark, George R.

2001-01-01

Although Stat1 is essential for cells to respond fully to IFN-γ, there is substantial evidence that, in the absence of Stat1, IFN-γ can still regulate the expression of some genes, induce an antiviral state and affect cell growth. We have now identified many genes that are regulated by IFN-γ in serum-starved Stat1-null mouse fibroblasts. The proteins induced by IFN-γ in Stat1-null cells can account for the substantial biological responses that remain. Some genes are induced in both wild-type and Stat1-null cells and thus are truly Stat1-independent. Others are subject to more complex regulation in response to IFN-γ, repressed by Stat1 in wild-type cells and activated in Stat1-null cells. Many genes induced by IFN-γ in Stat1-null fibroblasts also are induced by platelet-derived growth factor in wild-type cells and thus are likely to be involved in cell proliferation. In mouse cells expressing the docking site mutant Y440F of human IFN-γ receptor subunit 1, the mouse Stat1 is not phosphorylated in response to human IFN-γ, but c-myc and c-jun are still induced, showing that the Stat1 docking site is not required for Stat1-independent signaling. PMID:11390994

On the structure of finite-sheeted coverings of compact connected groups

OpenAIRE

Grigorian, S. A.; Gumerov, R. N.

2004-01-01

Finite-sheeted covering mappings onto compact connected groups are studied. It is shown that a finite-sheeted covering mapping from a connected Hausdorff topological space onto a compact connected abelian group G must be a homeomorphism provided that the character group of G admits division by the degree of given covering mapping. Using this result, we obtain criteria of triviality for finite coverings of G in terms of its character group and means on G. In order to establish these facts, for...

Stat1 phosphorylation determines Ras oncogenicity by regulating p27 kip1.

Directory of Open Access Journals (Sweden)

Shuo Wang

Full Text Available Inactivation of p27 Kip1 is implicated in tumorigenesis and has both prognostic and treatment-predictive values for many types of human cancer. The transcription factor Stat1 is essential for innate immunity and tumor immunosurveillance through its ability to act downstream of interferons. Herein, we demonstrate that Stat1 functions as a suppressor of Ras transformation independently of an interferon response. Inhibition of Ras transformation and tumorigenesis requires the phosphorylation of Stat1 at tyrosine 701 but is independent of Stat1 phosphorylation at serine 727. Stat1 induces p27 Kip1 expression in Ras transformed cells at the transcriptional level through mechanisms that depend on Stat1 phosphorylation at tyrosine 701 and activation of Stat3. The tumor suppressor properties of Stat1 in Ras transformation are reversed by the inactivation of p27 Kip1. Our work reveals a novel functional link between Stat1 and p27 Kip1, which act in coordination to suppress the oncogenic properties of activated Ras. It also supports the notion that evaluation of Stat1 phosphorylation in human tumors may prove a reliable prognostic factor for patient outcome and a predictor of treatment response to anticancer therapies aimed at activating Stat1 and its downstream effectors.

STAT3 mediates regorafenib-induced apoptosis in hepatocellular carcinoma.

Science.gov (United States)

Tai, Wei-Tien; Chu, Pei-Yi; Shiau, Chung-Wai; Chen, Yao-Li; Li, Yong-Shi; Hung, Man-Hsin; Chen, Li-Ju; Chen, Pei-Lung; Su, Jung-Chen; Lin, Ping-Yi; Yu, Hui-Chuan; Chen, Kuen-Feng

2014-11-15

Here, we aim to investigate the molecular mechanism of regorafenib and verify the potential druggable target for the treatment of hepatocellular carcinoma (HCC). HCC cell lines (PLC5, HepG2, Hep3B, SK-Hep1, and HA59T) were used to investigate the in vitro effect of regorafenib. Phosphatase activity was analyzed in HCC cells and purified SHP-1 proteins. PLC5-bearing mice were used to test the therapeutic efficiency of 20 and 40 mg/kg/d treatment with regorafenib ([Formula: see text] mice). The clinical relevance of STAT3 signaling was investigated with 142 tumor samples from different patients with HCC. Descriptive statistical analysis was used to compare the baseline characteristics of patients and the expression of p-STAT3. Regorafenib inhibited STAT3-related signaling in a dose-dependent manner and was a more potent inhibitor of STAT3 than sorafenib. Regorafenib increased SHP-1 phosphatase activity in purified SHP-1 protein directly. N-SH2 domain deletion and D61A mutants mimicking open-form SHP-1 partially abolished regorafenib-induced STAT3 inhibition and apoptosis. Importantly, a higher level of expression of STAT3 was found in patients with advanced clinical stages (P = 0.009) and poorly differentiated tumors (P = 0.035). Regorafenib induced significant tumor inhibition by relieving the autoinhibited N-SH2 domain of SHP-1 directly and inhibiting p-STAT3 signals. STAT3 may be suitable as a prognostic marker of HCC development, and may be a druggable target for HCC-targeted therapy using regorafenib. ©2014 American Association for Cancer Research.

Solar 101 STAT Webinars | State, Local, and Tribal Governments | NREL

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101 STAT Webinars Solar 101 STAT Webinars The Solar 101 series represents the foundation of the Solar Technical Assistance Team (STAT) webinars, which are organized by the DOE Solar Office in coordination with the National Renewable Energy Laboratory (NREL). The following sessions are available: Solar

Cross-talk between KLF4 and STAT3 regulates axon regeneration

Science.gov (United States)

Qin, Song; Zou, Yuhua; Zhang, Chun-Li

2013-10-01

Cytokine-induced activation of signal transducer and activator of transcription 3 (STAT3) promotes the regrowth of damaged axons in the adult central nervous system (CNS). Here we show that KLF4 physically interacts with STAT3 upon cytokine-induced phosphorylation of tyrosine 705 (Y705) on STAT3. This interaction suppresses STAT3-dependent gene expression by blocking its DNA-binding activity. The deletion of KLF4 in vivo induces axon regeneration of adult retinal ganglion cells (RGCs) via Janus kinase (JAK)-STAT3 signalling. This regeneration can be greatly enhanced by exogenous cytokine treatment, or removal of an endogenous JAK-STAT3 pathway inhibitor called suppressor of cytokine signalling 3 (SOCS3). These findings reveal an unexpected cross-talk between KLF4 and activated STAT3 in the regulation of axon regeneration that might have therapeutic implications in promoting repair of injured adult CNS.

Cyclophilins contribute to Stat3 signaling and survival of multiple myeloma cells.

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Bauer, K; Kretzschmar, A K; Cvijic, H; Blumert, C; Löffler, D; Brocke-Heidrich, K; Schiene-Fischer, C; Fischer, G; Sinz, A; Clevenger, C V; Horn, F

2009-08-06

Signal transducer and activator of transcription 3 (Stat3) is the major mediator of interleukin-6 (IL-6) family cytokines. In addition, Stat3 is known to be involved in the pathophysiology of many malignancies. Here, we show that the cis-trans peptidyl-prolyl isomerase cyclophilin (Cyp) B specifically interacts with Stat3, whereas the highly related CypA does not. CypB knockdown inhibited the IL-6-induced transactivation potential but not the tyrosine phosphorylation of Stat3. Binding of CypB to Stat3 target promoters and alteration of the intranuclear localization of Stat3 on CypB depletion suggested a nuclear function of Stat3/CypB interaction. By contrast, CypA knockdown inhibited Stat3 IL-6-induced tyrosine phosphorylation and nuclear translocation. The Cyp inhibitor cyclosporine A (CsA) caused similar effects. However, Stat1 activation in response to IL-6 or interferon-gamma was not affected by Cyp silencing or CsA treatment. As a result, Cyp knockdown shifted IL-6 signaling to a Stat1-dominated pathway. Furthermore, Cyp depletion or treatment with CsA induced apoptosis in IL-6-dependent multiple myeloma cells, whereas an IL-6-independent line was not affected. Thus, Cyps support the anti-apoptotic action of Stat3. Taken together, CypA and CypB both play pivotal roles, yet at different signaling levels, for Stat3 activation and function. These data also suggest a novel mechanism of CsA action.

Epstein-Barr virus-derived EBNA2 regulates STAT3 activation

International Nuclear Information System (INIS)

Muromoto, Ryuta; Ikeda, Osamu; Okabe, Kanako; Togi, Sumihito; Kamitani, Shinya; Fujimuro, Masahiro; Harada, Shizuko; Oritani, Kenji; Matsuda, Tadashi

2009-01-01

The Epstein-Barr virus (EBV)-encoded latency protein EBNA2 is a nuclear transcriptional activator that is essential for EBV-induced cellular transformation. Here, we show that EBNA2 interacts with STAT3, a signal transducer for an interleukin-6 family cytokine, and enhances the transcriptional activity of STAT3 by influencing its DNA-binding activity. Furthermore, EBNA2 cooperatively acts on STAT3 activation with LMP1. These data demonstrate that EBNA2 acts as a transcriptional coactivator of STAT3.

STAT4 gene polymorphism in patients after renal allograft transplantation

OpenAIRE

D?browska-?amojcin, Ewa; Dziedziejko, Violetta; Safranow, Krzysztof; Doma?ski, Leszek; S?uczanowska-G?abowska, Sylwia; Pawlik, Andrzej

2016-01-01

Introduction STAT4 (signal transducer and activator of transcription 4) is involved in the regulation of innate and adaptive immune responses. Some studies have suggested that STAT4 may be involved in the immune response after graft transplantation. Several polymorphisms in the STAT4 gene have been identified. The most commonly studied polymorphism in the STAT4 gene is rs7574865. In our study, we examined whether this polymorphism is associated with the early and late functions of renal allog...

Novel multiplexed assay for identifying SH2 domain antagonists of STAT family proteins.

Science.gov (United States)

Takakuma, Kazuyuki; Ogo, Naohisa; Uehara, Yutaka; Takahashi, Susumu; Miyoshi, Nao; Asai, Akira

2013-01-01

Some of the signal transducer and activator of transcription (STAT) family members are constitutively activated in a wide variety of human tumors. The activity of STAT depends on their Src homology 2 (SH2) domain-mediated binding to sequences containing phosphorylated tyrosine. Thus, antagonizing this binding is a feasible approach to inhibiting STAT activation. We have developed a novel multiplexed assay for STAT3- and STAT5b-SH2 binding, based on amplified luminescent proximity homogeneous assay (Alpha) technology. AlphaLISA and AlphaScreen beads were combined in a single-well assay, which allowed the binding of STAT3- and STAT5b-SH2 to phosphotyrosine peptides to be simultaneously monitored. Biotin-labeled recombinant human STAT proteins were obtained as N- and C-terminal deletion mutants. The spacer length of the DIG-labeled peptide, the reaction time, and the concentration of sodium chloride were optimized to establish a HTS system with Z' values of greater than 0.6 for both STAT3- and STAT5b-SH2 binding. We performed a HTS campaign for chemical libraries using this multiplexed assay and identified hit compounds. A 2-chloro-1,4-naphthalenedione derivative, Compound 1, preferentially inhibited STAT3-SH2 binding in vitro, and the nuclear translocation of STAT3 in HeLa cells. Initial structure activity relationship (SAR) studies using the multiplexed assay showed the 3-substituent effect on both the activity and selectivity of STAT3 and STAT5b inhibition. Therefore, this multiplexed assay is useful for not only searching for potential lead compounds but also obtaining SAR data for developing new STAT3/STAT5b inhibitors.

Facts on Nirex

International Nuclear Information System (INIS)

1987-01-01

This folder contains twelve two-page leaflets (fact sheets) which answer questions posed about UK NIREX Ltd, its operations and radioactive waste. NIREX (the Nuclear Industry Radioactive Waste Executive) is the organisation responsible for implementing the British Government's policy for the disposal of most low- and intermediate-level radioactive waste produced in the United Kingdom. The questions posed are; what is NIREX. What is radioactivity. What is radioactive waste. Radioactive waste, what are the options. What is a radioactive waste repository. Some aspects of such a repository are then explained - how engineered barriers work, how geological barriers work, how long can concrete last, how is the radioactive waste transported, how are repository sites identified. The last two leaflets consider why do we need research, and look at radioactive waste management worldwide. The answers are in non-technical language and are short. (UK)

Dynamic trafficking of STAT5 depends on an unconventional nuclear localization signal

Science.gov (United States)

Shin, Ha Youn; Reich, Nancy C.

2013-01-01

Summary Signal transducer and activator of transcription 5 (STAT5) is crucial for physiological processes that include hematopoiesis, liver metabolism and mammary gland development. However, aberrant continual activity of STAT5 has been causally linked to human leukemias and solid tumor formation. As a regulated transcription factor, precise cellular localization of STAT5 is essential. Conventional nuclear localization signals consist of short stretches of basic amino acids. In this study, we provide evidence that STAT5 nuclear import is dependent on an unconventional nuclear localization signal that functions within the conformation of an extensive coiled-coil domain. Both in vitro binding and in vivo functional assays reveal that STAT5 nuclear import is mediated by the importin-α3/β1 system independently of STAT5 activation by tyrosine phosphorylation. The integrity of the coiled-coil domain is essential for STAT5 transcriptional induction of the β-casein gene following prolactin stimulation as well as its ability to synergize with the glucocorticoid receptor. The glucocorticoid receptor accumulates in the nucleus in response to prolactin and this nuclear import is dependent on STAT5 nuclear import. STAT5 continually shuttles in and out of the nucleus and live cell imaging demonstrates that STAT5 nuclear export is mediated by both chromosome region maintenance 1 (Crm1)-dependent and Crm1-independent pathways. A Crm1-dependent nuclear export signal was identified within the STAT5 N-terminus. These findings provide insight into the fundamental mechanisms that regulate STAT5 nuclear trafficking and cooperation with the glucocorticoid receptor and provide a basis for clinical intervention of STAT5 function in disease. PMID:23704351

STAT3 can be activated through paracrine signaling in breast epithelial cells

International Nuclear Information System (INIS)

Lieblein, Jacqueline C; Ball, Sarah; Hutzen, Brian; Sasser, A Kate; Lin, Huey-Jen; Huang, Tim HM; Hall, Brett M; Lin, Jiayuh

2008-01-01

Many cancers, including breast cancer, have been identified with increased levels of phosphorylated or the active form of Signal Transducers and Activators of Transcription 3 (STAT3) protein. However, whether the tumor microenvironment plays a role in this activation is still poorly understood. Conditioned media, which contains soluble factors from MDA-MB-231 and MDA-MB-468 breast cancer cells and breast cancer associated fibroblasts, was added to MCF-10A breast epithelial and MDA-MB-453 breast cancer cells. The stimulation of phosphorylated STAT3 (p-STAT3) levels by conditioned media was assayed by Western blot in the presence or absence of neutralized IL-6 antibody, or a JAK/STAT3 inhibitor, JSI-124. The stimulation of cell proliferation in MCF-10A cells by conditioned media in the presence or absence of JSI-124 was subjected to MTT analysis. IL-6, IL-10, and VEGF levels were determined by ELISA analysis. Our results demonstrated that conditioned media from cell lines with constitutively active STAT3 are sufficient to induce p-STAT3 levels in various recipients that do not possess elevated p-STAT3 levels. This signaling occurs through the JAK/STAT3 pathway, leading to STAT3 phosphorylation as early as 30 minutes and is persistent for at least 24 hours. ELISA analysis confirmed a correlation between elevated levels of IL-6 production and p-STAT3. Neutralization of the IL-6 ligand or gp130 was sufficient to block increased levels of p-STAT3 (Y705) in treated cells. Furthermore, soluble factors within the MDA-MB-231 conditioned media were also sufficient to stimulate an increase in IL-6 production from MCF-10A cells. These results demonstrate STAT3 phosphorylation in breast epithelial cells can be stimulated by paracrine signaling through soluble factors from both breast cancer cells and breast cancer associated fibroblasts with elevated STAT3 phosphorylation. The induction of STAT3 phosphorylation is through the IL-6/JAK pathway and appears to be associated with

Novel high-throughput screening system for identifying STAT3-SH2 antagonists

International Nuclear Information System (INIS)

Uehara, Yutaka; Mochizuki, Masato; Matsuno, Kenji; Haino, Takeharu; Asai, Akira

2009-01-01

Constitutive activation of the oncogenic transcription factor STAT3 frequently occurs in various human malignancies. STAT3 activation involves dimerization via intermolecular pTyr-SH2 interaction. Thus, antagonizing this interaction is a feasible approach to inhibit STAT3 activation for cancer therapy. In order to identify selective STAT3 inhibitors, we developed a biochemical HTS system based on AlphaScreen technology, which measures the abilities of test compounds to antagonize pTyr-SH2 interactions. We screened our chemical libraries using this system and identified 5,15-diphenylporphyrin (5,15-DPP) as a selective STAT3-SH2 antagonist. Selective inhibition of STAT3 nuclear translocation and DNA biding activity was observed in cells treated with 5,15-DPP. IL-6-dependent dimerization of STAT3, c-myc promoter binding and c-myc protein expression were all suppressed by 5,15-DPP, whereas no decrement in either expression or phosphorylation level of STAT3 was observed. Thus, the HTS assay system represented herein may be useful for identifying novel STAT3-SH2 antagonists.

The JAK/STAT pathway in obesity and diabetes.

Science.gov (United States)

Gurzov, Esteban N; Stanley, William J; Pappas, Evan G; Thomas, Helen E; Gough, Daniel J

2016-08-01

Diabetes mellitus are complex, multi-organ metabolic pathologies characterized by hyperglycemia. Emerging evidence shows that the highly conserved and potent JAK/STAT signaling pathway is required for normal homeostasis, and, when dysregulated, contributes to the development of obesity and diabetes. In this review, we analyze the role of JAK/STAT activation in the brain, liver, muscle, fat and pancreas, and how this affects the course of the disease. We also consider the therapeutic implications of targeting the JAK/STAT pathway in treatment of obesity and diabetes. © 2016 Federation of European Biochemical Societies.

Altered IFN-γ-mediated immunity and transcriptional expression patterns in N-Ethyl-N-nitrosourea-induced STAT4 mutants confer susceptibility to acute typhoid-like disease.

Science.gov (United States)

Eva, Megan M; Yuki, Kyoko E; Dauphinee, Shauna M; Schwartzentruber, Jeremy A; Pyzik, Michal; Paquet, Marilène; Lathrop, Mark; Majewski, Jacek; Vidal, Silvia M; Malo, Danielle

2014-01-01

Salmonella enterica is a ubiquitous Gram-negative intracellular bacterium that continues to pose a global challenge to human health. The etiology of Salmonella pathogenesis is complex and controlled by pathogen, environmental, and host genetic factors. In fact, patients immunodeficient in genes in the IL-12, IL-23/IFN-γ pathway are predisposed to invasive nontyphoidal Salmonella infection. Using a forward genomics approach by N-ethyl-N-nitrosourea (ENU) germline mutagenesis in mice, we identified the Ity14 (Immunity to Typhimurium locus 14) pedigree exhibiting increased susceptibility following in vivo Salmonella challenge. A DNA-binding domain mutation (p.G418_E445) in Stat4 (Signal Transducer and Activator of Transcription Factor 4) was the causative mutation. STAT4 signals downstream of IL-12 to mediate transcriptional regulation of inflammatory immune responses. In mutant Ity14 mice, the increased splenic and hepatic bacterial load resulted from an intrinsic defect in innate cell function, IFN-γ-mediated immunity, and disorganized granuloma formation. We further show that NK and NKT cells play an important role in mediating control of Salmonella in Stat4(Ity14/Ity14) mice. Stat4(Ity14/Ity14) mice had increased expression of genes involved in cell-cell interactions and communication, as well as increased CD11b expression on a subset of splenic myeloid dendritic cells, resulting in compromised recruitment of inflammatory cells to the spleen during Salmonella infection. Stat4(Ity14/Ity14) presented upregulated compensatory mechanisms, although inefficient and ultimately Stat4(Ity14/Ity14) mice develop fatal bacteremia. The following study further elucidates the pathophysiological impact of STAT4 during Salmonella infection.

Characterization of STAT3 activation and expression in canine and human osteosarcoma

Directory of Open Access Journals (Sweden)

Li Pui-Kai

2009-03-01

Full Text Available Abstract Background Dysregulation of signal transducer and activator of transcription 3 (STAT3 has been implicated as a key participant in tumor cell survival, proliferation, and metastasis and is often correlated with a more malignant tumor phenotype. STAT3 phosphorylation has been demonstrated in a subset of human osteosarcoma (OSA tissues and cell lines. OSA in the canine population is known to exhibit a similar clinical behavior and molecular biology when compared to its human counterpart, and is often used as a model for preclinical testing of novel therapeutics. The purpose of this study was to investigate the potential role of STAT3 in canine and human OSA, and to evaluate the biologic activity of a novel small molecule STAT3 inhibitor. Methods To examine STAT3 and Src expression in OSA, we performed Western blotting and RT-PCR. OSA cells were treated with either STAT3 siRNA or small molecule Src (SU6656 or STAT3 (LLL3 inhibitors and cell proliferation (CyQUANT, caspase 3/7 activity (ELISA, apoptosis (Western blotting for PARP cleavage and/or viability (Wst-1 were determined. Additionally, STAT3 DNA binding after treatment was determined using EMSA. Expression of STAT3 targets after treatment was demonstrated with Western blotting, RT-PCR, or gel zymography. Results Our data demonstrate that constitutive activation of STAT3 is present in a subset of canine OSA tumors and human and canine cell lines, but not normal canine osteoblasts. In both canine and human OSA cell lines, downregulation of STAT3 activity through inhibition of upstream Src family kinases using SU6656, inhibition of STAT3 DNA binding and transcriptional activities using LLL3, or modulation of STAT3 expression using siRNA, all resulted in decreased cell proliferation and viability, ultimately inducing caspase-3/7 mediated apoptosis in treated cells. Furthermore, inhibition of either Src or STAT3 activity downregulated the expression of survivin, VEGF, and MMP2, all known

Characterization of STAT3 activation and expression in canine and human osteosarcoma

International Nuclear Information System (INIS)

Fossey, Stacey L; Liao, Albert T; McCleese, Jennifer K; Bear, Misty D; Lin, Jiayuh; Li, Pui-Kai; Kisseberth, William C; London, Cheryl A

2009-01-01

Dysregulation of signal transducer and activator of transcription 3 (STAT3) has been implicated as a key participant in tumor cell survival, proliferation, and metastasis and is often correlated with a more malignant tumor phenotype. STAT3 phosphorylation has been demonstrated in a subset of human osteosarcoma (OSA) tissues and cell lines. OSA in the canine population is known to exhibit a similar clinical behavior and molecular biology when compared to its human counterpart, and is often used as a model for preclinical testing of novel therapeutics. The purpose of this study was to investigate the potential role of STAT3 in canine and human OSA, and to evaluate the biologic activity of a novel small molecule STAT3 inhibitor. To examine STAT3 and Src expression in OSA, we performed Western blotting and RT-PCR. OSA cells were treated with either STAT3 siRNA or small molecule Src (SU6656) or STAT3 (LLL3) inhibitors and cell proliferation (CyQUANT), caspase 3/7 activity (ELISA), apoptosis (Western blotting for PARP cleavage) and/or viability (Wst-1) were determined. Additionally, STAT3 DNA binding after treatment was determined using EMSA. Expression of STAT3 targets after treatment was demonstrated with Western blotting, RT-PCR, or gel zymography. Our data demonstrate that constitutive activation of STAT3 is present in a subset of canine OSA tumors and human and canine cell lines, but not normal canine osteoblasts. In both canine and human OSA cell lines, downregulation of STAT3 activity through inhibition of upstream Src family kinases using SU6656, inhibition of STAT3 DNA binding and transcriptional activities using LLL3, or modulation of STAT3 expression using siRNA, all resulted in decreased cell proliferation and viability, ultimately inducing caspase-3/7 mediated apoptosis in treated cells. Furthermore, inhibition of either Src or STAT3 activity downregulated the expression of survivin, VEGF, and MMP2, all known transcriptional targets of STAT3. These data

The measles virus phosphoprotein interacts with the linker domain of STAT1

International Nuclear Information System (INIS)

Devaux, Patricia; Priniski, Lauren; Cattaneo, Roberto

2013-01-01

The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway. - Highlights: • Residue in the linker and SH2 domains of STAT1 are important for MV-P interaction. • Residue in the linker and SH2 domains of STAT1 are important for STAT1 phosphorylation. • Residues interferring with both functions have similar location on STAT1. • The viral P and V proteins may operate in concert to inhibit the JAK/STAT pathway

The measles virus phosphoprotein interacts with the linker domain of STAT1

Energy Technology Data Exchange (ETDEWEB)

Devaux, Patricia, E-mail: devaux.patricia@mayo.edu; Priniski, Lauren; Cattaneo, Roberto

2013-09-15

The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway. - Highlights: • Residue in the linker and SH2 domains of STAT1 are important for MV-P interaction. • Residue in the linker and SH2 domains of STAT1 are important for STAT1 phosphorylation. • Residues interferring with both functions have similar location on STAT1. • The viral P and V proteins may operate in concert to inhibit the JAK/STAT pathway.

STAT1 pathway mediates amplification of metastatic potential and resistance to therapy.

Directory of Open Access Journals (Sweden)

Nikolai N Khodarev

Full Text Available BACKGROUND: Traditionally IFN/STAT1 signaling is connected with an anti-viral response and pro-apoptotic tumor-suppressor functions. Emerging functions of a constitutively activated IFN/STAT1 pathway suggest an association with an aggressive tumor phenotype. We hypothesized that tumor clones that constitutively overexpress this pathway are preferentially selected by the host microenvironment due to a resistance to STAT1-dependent cytotoxicity and demonstrate increased metastatic ability combined with increased resistance to genotoxic stress. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that clones of B16F1 tumors grown in the lungs of syngeneic C57BL/6 mice demonstrate variable transcriptional levels of IFN/STAT1 pathway expression. Tumor cells that constitutively overexpress the IFN/STAT1 pathway (STAT1(H genotype are selected by the lung microenvironment. STAT1(H tumor cells also demonstrate resistance to IFN-gamma (IFNgamma, ionizing radiation (IR, and doxorubicin relative to parental B16F1 and low expressors of the IFN/STAT1 pathway (STAT1(L genotype. Stable knockdown of STAT1 reversed the aggressive phenotype and decreased both lung colonization and resistance to genotoxic stress. CONCLUSIONS: Our results identify a pathway activated by tumor-stromal interactions thereby selecting for pro-metastatic and therapy-resistant tumor clones. New therapies targeted against the IFN/STAT1 signaling pathway may provide an effective strategy to treat or sensitize aggressive tumor clones to conventional cancer therapies and potentially prevent distant organ colonization.

FastStats: Contraceptive Use

Science.gov (United States)

... Growth (data are for 2011-2015) Related FastStats Infertility Reproductive Health More data Condom Use During Sexual Intercourse Among Females and Males 15-44 in the United States [PDF – 430 ...

Analysis of signal transducer and activator of transcription 3 (Stat 3) pathway in multiple myeloma: Stat 3 activation and cyclin D1 dysregulation are mutually exclusive events.

Science.gov (United States)

Quintanilla-Martinez, Leticia; Kremer, Marcus; Specht, Katja; Calzada-Wack, Julia; Nathrath, Michaela; Schaich, Robert; Höfler, Heinz; Fend, Falko

2003-05-01

The signal transducer and activator of transcription molecules (Stats) play key roles in cytokine-induced signal transduction. Recently, it was proposed that constitutively activated Stat 3 (Stat 3 phosphorylated) contributes to the pathogenesis of multiple myeloma (MM) by preventing apoptosis and inducing proliferation. The study aim was to investigate Stat 3 activation in a series of multiple myeloma (MM) cases and its effect on downstream targets such as the anti-apoptotic proteins Bcl-xL, Mcl-1, and Bcl-2, and the cell-cycle protein cyclin D1. Forty-eight cases of MM were analyzed. Immunohistochemistry was performed on paraffin sections using antibodies against cyclin D1, Bcl-2, Bcl-xL, Mcl-1, p21, Stat 3, and Stat 3 phosphorylated (P). Their specificity was corroborated by Western blot analysis using eight human MM cell lines as control. The proliferation rate was assessed with the antibody MiB1. In addition, the mRNA levels of cyclin D1 and Stat 3 were determined by quantitative real-time reverse transcriptase-polymerase chain reaction of paraffin-embedded microdissected tissue. Three different groups determined by the expression of Stat 3P and cyclin D1 (protein and mRNA) were identified: group 1, Stat 3-activated (23 cases, 48%). All cases revealed nuclear expression of Stat 3P. No elevation of Stat 3 mRNA was identified in any of the cases. Three cases in this group showed intermediate to low cyclin D1 protein and mRNA expression. Group 2 included 15 (31%) cases with cyclin D1 staining and lack of Stat 3P. All cases showed intermediate to high levels of cyclin D1 mRNA expression. Group 3 included 10 (21%) cases with no expression of either cyclin D1 or Stat 3P. High levels of anti-apoptotic proteins Bcl-xL and Mcl-1 were identified in 89% and 100% of all cases, respectively. In contrast to Bcl-xL and Mcl-1, the expression of Bcl-2 showed an inverse correlation with proliferation rate (P: 0.0003). No significant differences were found between the three

Direct targets of pSTAT5 signalling in erythropoiesis.

Directory of Open Access Journals (Sweden)

Kevin R Gillinder

Full Text Available Erythropoietin (EPO acts through the dimeric erythropoietin receptor to stimulate proliferation, survival, differentiation and enucleation of erythroid progenitor cells. We undertook two complimentary approaches to find EPO-dependent pSTAT5 target genes in murine erythroid cells: RNA-seq of newly transcribed (4sU-labelled RNA, and ChIP-seq for pSTAT5 30 minutes after EPO stimulation. We found 302 pSTAT5-occupied sites: ~15% of these reside in promoters while the rest reside within intronic enhancers or intergenic regions, some >100kb from the nearest TSS. The majority of pSTAT5 peaks contain a central palindromic GAS element, TTCYXRGAA. There was significant enrichment for GATA motifs and CACCC-box motifs within the neighbourhood of pSTAT5-bound peaks, and GATA1 and/or KLF1 co-occupancy at many sites. Using 4sU-RNA-seq we determined the EPO-induced transcriptome and validated differentially expressed genes using dynamic CAGE data and qRT-PCR. We identified known direct pSTAT5 target genes such as Bcl2l1, Pim1 and Cish, and many new targets likely to be involved in driving erythroid cell differentiation including those involved in mRNA splicing (Rbm25, epigenetic regulation (Suv420h2, and EpoR turnover (Clint1/EpsinR. Some of these new EpoR-JAK2-pSTAT5 target genes could be used as biomarkers for monitoring disease activity in polycythaemia vera, and for monitoring responses to JAK inhibitors.

STAT6 Mediates Interleukin-4 Growth Inhibition in Human Breast Cancer Cells

Directory of Open Access Journals (Sweden)

Jennifer L. Gooch

2002-01-01

Full Text Available In addition to acting as a hematopoietic growth factor, interleukin-4 (IL-4 inhibits growth of some transformed cells in vitro and in vivo. In this study, we show that insulin receptor substrate (IRS-1, IRS-2, and signal transducer and activator of transcription 6 (STAT6 are phosphorylated following IL-4 treatment in MCF-7 breast cancer cells. STAT6 DNA binding is enhanced by IL-4 treatment. STAT6 activation occurs even after IRS-1 depletion, suggesting the two pathways are independent. To examine the role of STAT6 in IL-4-mediated growth inhibition and apoptosis, a fulllength STAT6 cDNA was transfected into MCF-7 cells. Transient overexpression of STAT6 resulted in both cytoplasmic and nuclear expression of the protein, increased DNA binding in response to IL-4, and increased transactivation of an IL-4 responsive promoter. In STAT6-transfected cells, basal proliferation was reduced whereas apoptosis was increased. Finally, stable expression of STAT6 resulted in reduced foci formation compared to vector-transfected cells alone. These results suggest STAT6 is required for IL-4mediated growth inhibition and induction of apoptosis in human breast cancer cells.

Assisted crack tip flipping under Mode I thin sheet tearing

DEFF Research Database (Denmark)

Felter, Christian Lotz; Nielsen, Kim Lau

2017-01-01

Crack tip flipping, where the fracture surface alternates from side to side in roughly 45° shear bands, seems to be an overlooked propagation mode in Mode I thin sheet tearing. In fact, observations of crack tip flipping is rarely found in the literature. Unlike the already established modes...

Interleukin 2 and 15 activate Stat3alpha in human T lymphocytes

DEFF Research Database (Denmark)

Nielsen, M; Nordahl, M; Svejgaard, A

1998-01-01

Signal transducer and activator of transcription 3 (Stat3) has recently been shown to exist in two alternatively spliced isoforms, a short form, Stat3beta, and a longer form, Stat3alpha, displaying differences in transcriptional activity. It is unknown which Stat3 isoform(s) is activated in respo...

Expression and Purification of Soluble STAT5b/STAT3 Proteins for SH2 Domain Binding Assay.

Science.gov (United States)

Asai, Akira; Takakuma, Kazuyuki

2017-01-01

When a large hydrophobic full-length protein is expressed in bacteria, it is often challenging to obtain recombinant proteins in the soluble fraction. One way to overcome this challenge is expression of deletion mutants that have improved solubility while maintaining biological activity. In this chapter, we describe a protocol for expression of truncated forms of STAT5b and STAT3 proteins that are soluble and retain SH2-mediated activity for phospho-Tyr peptide recognition.

Proinflammatory Cytokines IL-6 and TNF-α Increased Telomerase Activity through NF-κB/STAT1/STAT3 Activation, and Withaferin A Inhibited the Signaling in Colorectal Cancer Cells

Directory of Open Access Journals (Sweden)

Seyung S. Chung

2017-01-01

Full Text Available There are increasing evidences of proinflammatory cytokine involvement in cancer development. Here, we found that two cytokines, IL-6 and TNF-α, activated colorectal cancer cells to be more invasive and stem-like. Combined treatment of IL-6 and TNF-α phosphorylated transcription factors STAT3 in a synergistic manner. STAT3, STAT1, and NF-κB physically interacted upon the cytokine stimulation. STAT3 was bound to the promoter region of human telomerase reverse transcriptase (hTERT. IL-6 and TNF-α stimulation further enhanced STAT3 binding affinity. Stem cell marker Oct-4 was upregulated in colorectal cancer cells upon IL-6 and TNF-α stimulation. Withaferin A, an anti-inflammatory steroidal lactone, inhibited the IL-6- and TNF-α-induced cancer cell invasion and decreased colonosphere formation. Notably, withaferin A inhibited STAT3 phosphorylation and abolished the STAT3, STAT1, and NF-κB interactions. Oct-4 expression was also downregulated by withaferin A inhibition. The binding of STAT3 to the hTERT promoter region and telomerase activity showed reduction with withaferin A treatments. Proinflammatory cytokine-induced cancer cell invasiveness is mediated by a STAT3-regulated mechanism in colorectal cancer cells. Our data suggest that withaferin A could be a promising anticancer agent that effectively inhibits the progression of colorectal cancer.

FastStats: Body Measurements

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... this? Submit What's this? Submit Button NCHS Home Body Measurements Recommend on Facebook Tweet Share Compartir Data ... 7 MB] Related FastStats Obesity/Overweight Related Links Body Mass Index table CDC Growth Charts National Health ...

STAT3 inhibitor enhances chemotherapy drug efficacy by ...

African Journals Online (AJOL)

Immunohistochemistry and Kaplan-Meier method of survival analysis were used to determine chemoresistance trends in patients. STAT3 inhibitor treatment, RNAi or ectopic overexpression of STAT3 or MUC1 in NSCLC cells were used to determine their inter-molecular relation and for modulating stemness-related genes.

FastStats: Mental Health

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... Women’s Health State and Territorial Data Reproductive Health Contraceptive Use Infertility Reproductive Health Notice Regarding FastStats Mobile ... Use of Selected Nonmedication Mental Health Services by Adolescent Boys and Girls With Serious Emotional or Behavioral ...

Impaired IL-13-mediated functions of macrophages in STAT6-deficient mice.

Science.gov (United States)

Takeda, K; Kamanaka, M; Tanaka, T; Kishimoto, T; Akira, S

1996-10-15

IL-13 shares many biologic responses with IL-4. In contrast to well-characterized IL-4 signaling pathways, which utilize STAT6 and 4PS/IRS2, IL-13 signaling pathways are poorly understood. Recent studies performed with STAT6-deficient mice have demonstrated that STAT6 plays an essential role in IL-4 signaling. In this study, the functions of peritoneal macrophages of STAT6-deficient mice in response to IL-13 were analyzed. In STAT6-deficient mice, neither morphologic changes nor augmentation of MHC class II expression in response to IL-13 was observed. In addition, IL-13 did not decrease the nitric oxide production by activated macrophages. Taken together, these results suggest that the macrophage functions in response to IL-13 were impaired in STAT6-deficient mice, indicating that IL-13 and IL-4 share the signaling pathway via STAT6.

Evolution in Many-Sheeted Space-time

OpenAIRE

Pitkänen, Matti

2010-01-01

The topics of the article has been restricted to those, which seem to represent the most well-established ideas about evolution in many-sheeted space-time. a) Basic facts about and TGD based model for pre-biotic evolution are discussed. b) A model for the ATP-ADP process based on DNA as topological quantum computer vision, the identification of universal metabolic energy quanta in terms of zero point kinetic energies, and the notion of remote metabolism is discussed. c) A model f...

STAT3 and the Hyper-IgE syndrome

DEFF Research Database (Denmark)

Mogensen, Trine H

2013-01-01

somatic manifestations. In 2007 the genetic basis of HIES was revealed by identification of dominant negative STAT3 mutations in HIES patients. Subsequently impaired function of Tyk2 and DOCK8 have been implicated in milder forms of HIES. Since STAT3 acts as a central transcription factor downstream...

Facts and Stats - Hydrocephalus Association

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... this in Theme Options SIGN IN File Download Verification Thank you for downloading our publication! We will ... I am ...: Child Friend Grandchild Grandparent Medical Professional Self Sibling Parent Spouse Other Patient Diagnosed Age: Infants ( ...

Inhibition of DNA methyltransferase induces G2 cell cycle arrest and apoptosis in human colorectal cancer cells via inhibition of JAK2/STAT3/STAT5 signalling.

Science.gov (United States)

Xiong, Hua; Chen, Zhao-Fei; Liang, Qin-Chuan; Du, Wan; Chen, Hui-Min; Su, Wen-Yu; Chen, Guo-Qiang; Han, Ze-Guang; Fang, Jing-Yuan

2009-09-01

DNA methyltransferase inhibitors (MTIs) have recently emerged as promising chemotherapeutic or preventive agents for cancer, despite their poorly characterized mechanisms of action. The present study shows that DNA methylation is integral to the regulation of SH2-containing protein tyrosine phosphatase 1 (SHP1) expression, but not for regulation of suppressors of cytokine signalling (SOCS)1 or SOCS3 in colorectal cancer (CRC) cells. SHP1 expression correlates with down-regulation of Janus kinase/signal transducers and activators of transcription (JAK2/STAT3/STAT5) signalling, which is mediated in part by tyrosine dephosphorylation events and modulation of the proteasome pathway. Up-regulation of SHP1 expression was achieved using a DNA MTI, 5-aza-2'-deoxycytidine (5-aza-dc), which also generated significant down-regulation of JAK2/STAT3/STAT5 signalling. We demonstrate that 5-aza-dc suppresses growth of CRC cells, and induces G2 cell cycle arrest and apoptosis through regulation of downstream targets of JAK2/STAT3/STAT5 signalling including Bcl-2, p16(ink4a), p21(waf1/cip1) and p27(kip1). Although 5-aza-dc did not significantly inhibit cell invasion, 5-aza-dc did down-regulate expression of focal adhesion kinase and vascular endothelial growth factor in CRC cells. Our results demonstrate that 5-aza-dc can induce SHP1 expression and inhibit JAK2/STAT3/STAT5 signalling. This study represents the first evidence towards establishing a mechanistic link between inhibition of JAK2/STAT3/STAT5 signalling and the anticancer action of 5-aza-dc in CRC cells that may lead to the use of MTIs as a therapeutic intervention for human colorectal cancer.

Suppression of STAT3 NH2 -terminal domain chemosensitizes medulloblastoma cells by activation of protein inhibitor of activated STAT3 via de-repression by microRNA-21.

Science.gov (United States)

Ray, Sutapa; Coulter, Don W; Gray, Shawn D; Sughroue, Jason A; Roychoudhury, Shrabasti; McIntyre, Erin M; Chaturvedi, Nagendra K; Bhakat, Kishor K; Joshi, Shantaram S; McGuire, Timothy R; Sharp, John G

2018-04-01

Medulloblastoma (MB) is a malignant pediatric brain tumor with poor prognosis. Signal transducers and activators of transcription-3 (STAT3) is constitutively activated in MB where it functions as an oncoprotein, mediating cancer progression and metastasis. Here, we have delineated the functional role of activated STAT3 in MB, by using a cell permeable STAT3-NH 2 terminal domain inhibitor (S3-NTDi) that specifically perturbs the structure/function of STAT3. We have implemented several biochemical experiments using human MB tumor microarray (TMA) and pediatric MB cell lines, derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/SHH tumors. Treatment of MB cells with S3-NTDi leads to growth inhibition, cell cycle arrest, and apoptosis. S3-NTDi downregulated expression of STAT3 target genes, delayed migration of MB cells, attenuated epithelial-mesenchymal transition (EMT) marker expressions and reduced cancer stem-cell associated protein expressions in MB-spheres. To elucidate mechanisms, we showed that S3-NTDi induce expression of pro-apoptotic gene, C/EBP-homologous protein (CHOP), and decrease association of STAT3 to the proximal promoter of CCND1 and BCL2. Of note, S3-NTDi downregulated microRNA-21, which in turn, de-repressed Protein Inhibitor of Activated STAT3 (PIAS3), a negative regulator of STAT3 signaling pathway. Furthermore, combination therapy with S3-NTDi and cisplatin significantly decreased highly aggressive MYC-amplified MB cell growth and induced apoptosis by downregulating STAT3 regulated proliferation and anti-apoptotic gene expression. Together, our results revealed an important role of STAT3 in regulating MB pathogenesis. Disruption of this pathway with S3-NTDi, therefore, may serves as a promising candidate for targeted MB therapy by enhancing chemosensitivity of MB cells and potentially improving outcomes in high-risk patients. © 2017 Wiley Periodicals, Inc.

Antagonizing STAT3 dimerization with a rhodium(III) complex.

Science.gov (United States)

Ma, Dik-Lung; Liu, Li-Juan; Leung, Ka-Ho; Chen, Yen-Ting; Zhong, Hai-Jing; Chan, Daniel Shiu-Hin; Wang, Hui-Min David; Leung, Chung-Hang

2014-08-25

Kinetically inert metal complexes have arisen as promising alternatives to existing platinum and ruthenium chemotherapeutics. Reported herein, to our knowledge, is the first example of a substitutionally inert, Group 9 organometallic compound as a direct inhibitor of signal transducer and activator of transcription 3 (STAT3) dimerization. From a series of cyclometalated rhodium(III) and iridium(III) complexes, a rhodium(III) complex emerged as a potent inhibitor of STAT3 that targeted the SH2 domain and inhibited STAT3 phosphorylation and dimerization. Significantly, the complex exhibited potent anti-tumor activities in an in vivo mouse xenograft model of melanoma. This study demonstrates that rhodium complexes may be developed as effective STAT3 inhibitors with potent anti-tumor activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

STAT6 deficiency ameliorates Graves' disease severity by suppressing thyroid epithelial cell hyperplasia.

Science.gov (United States)

Jiang, Xuechao; Zha, Bingbing; Liu, Xiaoming; Liu, Ronghua; Liu, Jun; Huang, Enyu; Qian, Tingting; Liu, Jiajing; Wang, Zhiming; Zhang, Dan; Wang, Luman; Chu, Yiwei

2016-12-01

Signal transducer and activator of transcription 6 (STAT6) is involved in epithelial cell growth. However, little is known regarding the STAT6 phosphorylation status in Graves' disease (GD) and its role in thyroid epithelial cells (TECs). In this study, we found that STAT6 phosphorylation (p-STAT6) was significantly increased in TECs from both GD patients and experimental autoimmune Graves' disease mice and that STAT6 deficiency ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the phosphorylation of STAT6 via IL-4 R engagement, and the downstream targets of STAT6 were Bcl-xL and cyclin D1. Thus, the IL-4-STAT6-Bcl-xL/cyclin D1 pathway is crucial for TEC hyperplasia, which aggravates GD. More importantly, in vitro and in vivo experiments demonstrated that STAT6 phosphorylation inhibited by AS1517499 decreased TEC hyperplasia, thereby reducing serum T3 and T4 and ameliorating GD. Thus, our study reveals that in addition to the traditional pathogenesis of GD, in which autoantibody TRAb stimulates thyroid-stimulating hormone receptors and consequently produces T3, T4, TRAb could also trigger TECs producing IL-4, and IL-4 then acts in an autocrine manner to activate p-STAT6 signalling and stimulate unrestricted cell growth, thus aggravating GD. These findings suggest that STAT6 inhibitors could be potent therapeutics for treating GD.

Stat3 induces oncogenic Skp2 expression in human cervical carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Huang, Hanhui [Shanghai Medical College of Fudan University, Shanghai 200032 (China); Zhao, Wenrong [Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011 (China); Yang, Dan, E-mail: yangdandr@gmail.com [Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University, Shanghai 200040 (China)

2012-02-03

Highlights: Black-Right-Pointing-Pointer Upregulation of Skp2 by IL-6 or Stat3 activation. Black-Right-Pointing-Pointer Stat3 activates Skp2 expression through bound to its promoter region. Black-Right-Pointing-Pointer Stat3 activates Skp2 expression through recruitment of P300. Black-Right-Pointing-Pointer Stat3 activation decreases the P27 stability. -- Abstract: Dysregulated Skp2 function promotes cell proliferation, which is consistent with observations of Skp2 over-expression in many types of human cancers, including cervical carcinoma (CC). However, the molecular mechanisms underlying elevated Skp2 expression have not been fully explored. Interleukin-6 (IL-6) induced Stat3 activation is viewed as crucial for multiple tumor growth and metastasis. Here, we demonstrate that Skp2 is a direct transcriptional target of Stat3 in the human cervical carcinoma cells. Our data show that IL-6 administration or transfection of a constitutively activated Stat3 in HeLa cells activates Skp2 mRNA transcription. Using luciferase reporter and ChIP assays, we show that Stat3 binds to the promoter region of Skp2 and promotes its activity through recruiting P300. As a result of the increase of Skp2 expression, endogenous p27 protein levels are markedly decreased. Thus, our results suggest a previously unknown Stat3-Skp2 molecular network controlling cervical carcinoma development.

STAT1, STAT3 and p38MAPK are involved in the apoptotic effect induced by a chimeric cyclic interferon-{alpha}2b peptide

Energy Technology Data Exchange (ETDEWEB)

Blank, Viviana C.; Pena, Clara [Institute of Biochemistry and Biophysics (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956-C1113AAD Buenos Aires (Argentina); Roguin, Leonor P., E-mail: rvroguin@qb.ffyb.uba.ar [Institute of Biochemistry and Biophysics (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956-C1113AAD Buenos Aires (Argentina)

2010-02-15

In the search of mimetic peptides of the interferon-{alpha}2b molecule (IFN-{alpha}2b), we have previously designed and synthesized a chimeric cyclic peptide of the IFN-{alpha}2b that inhibits WISH cell proliferation by inducing an apoptotic response. Here, we first studied the ability of this peptide to activate intracellular signaling pathways and then evaluated the participation of some signals in the induction of apoptosis. Stimulation of WISH cells with the cyclic peptide showed tyrosine phosphorylation of Jak1 and Tyk2 kinases, tyrosine and serine phosphorylation of STAT1 and STAT3 transcription factors and activation of p38 MAPK pathway, although phosphorylation levels or kinetics were in some conditions different to those obtained under IFN-{alpha}2b stimulus. JNK and p44/42 pathways were not activated by the peptide in WISH cells. We also showed that STAT1 and STAT3 downregulation by RNA interference decreased the antiproliferative activity and the amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.

STAT1, STAT3 and p38MAPK are involved in the apoptotic effect induced by a chimeric cyclic interferon-α2b peptide

International Nuclear Information System (INIS)

Blank, Viviana C.; Pena, Clara; Roguin, Leonor P.

2010-01-01

In the search of mimetic peptides of the interferon-α2b molecule (IFN-α2b), we have previously designed and synthesized a chimeric cyclic peptide of the IFN-α2b that inhibits WISH cell proliferation by inducing an apoptotic response. Here, we first studied the ability of this peptide to activate intracellular signaling pathways and then evaluated the participation of some signals in the induction of apoptosis. Stimulation of WISH cells with the cyclic peptide showed tyrosine phosphorylation of Jak1 and Tyk2 kinases, tyrosine and serine phosphorylation of STAT1 and STAT3 transcription factors and activation of p38 MAPK pathway, although phosphorylation levels or kinetics were in some conditions different to those obtained under IFN-α2b stimulus. JNK and p44/42 pathways were not activated by the peptide in WISH cells. We also showed that STAT1 and STAT3 downregulation by RNA interference decreased the antiproliferative activity and the amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.

Narcolepsy: Fact Sheet

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Respirator Fact Sheet

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CASA Fact Sheet.

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National Court Appointed Special Advocate Association, Seattle WA.

Each year nearly 400,000 children in the United States are thrust into court through no fault of their own. Often these children also become victims of the United States' overburdened child welfare system. A Court Appointed Special Advocate (CASA) volunteer is a trained citizen who is appointed by a judge to represent the best interests of a child…

Pharmacogenomics Fact Sheet

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... all prescription drugs. For example, it converts the painkiller codeine into its active form, morphine. There are ... patients by providing guidance on dose, possible side effects, or differences in effectiveness for people with certain ...

Penguin Fact Sheet.

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Flotsam and Jetsam: A Newsletter for Massachusetts Marine Educators, 1985

1985-01-01

Presents factual information on penguins using an outline format. Includes descriptions of physical characteristics, behavioral mechanisms, geographical distribution, and physiological processes. Provides separate bibliographies for teachers and students. (ML)

Stroke Fact Sheet

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Diabetes Fact Sheet

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Infertility Fact Sheet

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Burns Fact Sheet

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Trauma Fact Sheet

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STAT3 mutations correlated with hyper-IgE syndrome lead to ...

Indian Academy of Sciences (India)

Of all the causes identified for the disease hyper-immunoglobulinemia E syndrome (HIES), a homozygous mutation in tyrosine kinase2 (TYK2) and heterozygous mutations in STAT3 are implicated the defects in Jak/STAT signalling pathway in the pathogenesis of HIES. Mutations of STAT3 have been frequently clinically ...

STAT6: its role in interleukin 4-mediated biological functions.

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Takeda, K; Kishimoto, T; Akira, S

1997-05-01

Interleukin (IL) 4 is known to be a cytokine which plays a central role in the regulation of immune response. Studies on cytokine signal transduction have clarified the mechanism by which IL4 exerts its functions. Two cytoplasmic proteins, signal transducer and activator of transcription (STAT) 6 and IL4-induced phosphotyrosine substrate/insulin receptor substrate 2 (4PS/IRS2), are activated in IL4 signal transduction. Recent studies from STAT6-deficient mice have revealed the essential role of STAT6 in IL4-mediated biological actions. In addition, STAT6 has also been demonstrated to be important for the functions mediated by IL13, which is related to IL4. IL4 and IL13 have been shown to induce the production of IgE, which is a major mediator in an allergic response. These findings indicate that STAT6 activation is involved in IL4- and IL13-mediated disorders such as allergy.

KAP1 regulates type I interferon/STAT1-mediated IRF-1 gene expression

International Nuclear Information System (INIS)

Kamitani, Shinya; Ohbayashi, Norihiko; Ikeda, Osamu; Togi, Sumihito; Muromoto, Ryuta; Sekine, Yuichi; Ohta, Kazuhide; Ishiyama, Hironobu; Matsuda, Tadashi

2008-01-01

Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation, and survival in immune responses, hematopoiesis, neurogenesis, and other biological processes. Recently, we showed that KAP1 is a novel STAT-binding partner that regulates STAT3-mediated transactivation. KAP1 is a universal co-repressor protein for the KRAB zinc finger protein superfamily of transcriptional repressors. In this study, we found KAP1-dependent repression of interferon (IFN)/STAT1-mediated signaling. We also demonstrated that endogenous KAP1 associates with endogenous STAT1 in vivo. Importantly, a small-interfering RNA-mediated reduction in KAP1 expression enhanced IFN-induced STAT1-dependent IRF-1 gene expression. These results indicate that KAP1 may act as an endogenous regulator of the IFN/STAT1 signaling pathway

Bcl6 promotes osteoblastogenesis through Stat1 inhibition

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Fujie, Atsuhiro; Funayama, Atsushi; Miyauchi, Yoshiteru [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Sato, Yuiko [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Musculoskeletal Reconstruction and Regeneration Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Kobayashi, Tami [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Integrated Bone Metabolism and Immunology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Kanagawa, Hiroya; Katsuyama, Eri; Hao, Wu; Tando, Toshimi; Watanabe, Ryuichi [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Morita, Mayu [Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Miyamoto, Kana; Kanaji, Arihiko; Morioka, Hideo; Matsumoto, Morio; Toyama, Yoshiaki [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Miyamoto, Takeshi, E-mail: miyamoto@z5.keio.jp [Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan); Department of Integrated Bone Metabolism and Immunology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582 (Japan)

2015-02-13

Bone mass is tightly controlled by a balance between osteoclast and osteoblast activities. Although these cell types mature via different pathways, some factors reportedly regulate differentiation of both. Here, in a search for factors governing osteoblastogenesis but also expressed in osteoclasts to control both cell types by one molecule, we identified B cell lymphoma 6 (Bcl6) as one of those factors and show that it promotes osteoblast differentiation. Bcl6 was previously shown to negatively regulate osteoclastogenesis. We report that lack of Bcl6 results in significant inhibition of osteoblastogensis in vivo and in vitro and in defects in secondary ossification center formation in vivo. Signal transducer and activator of transcription 1 (Stat1) reportedly attenuates osteoblast differentiation by inhibiting nuclear translocation of runt-related transcription factor 2 (Runx2), which is essential for osteoblast differentiation. We found that lack of Bcl6 resulted in significant elevation of Stat1 mRNA and protein expression in osteoblasts and showed that Stat1 is a direct target of Bcl6 using a chromatin immune-precipitation assay. Mice lacking both Bcl6 and Stat1 (DKO) exhibited significant rescue of bone mass and osteoblastic parameters as well as partial rescue of secondary ossification center formation compared with Bcl6-deficient mice in vivo. Altered osteoblastogenesis in Bcl6-deficient cells was also restored in DKO in vitro. Thus, Bcl6 plays crucial roles in regulating both osteoblast activation and osteoclast inhibition. - Highlights: • Bcl6 is required for osteoblast differentiation. • Bcl6{sup −/−} mice exhibited altered osteoblastogenesis and reduced bone mass in vivo and in vitro. • We identified Stat1 as a direct target of Bcl6 in osteoblasts. • Bcl6 and Stat1 doubly deficient mice exhibited rescued bone phenotypes compared with Bcl6{sup −/−} mice.

Maths4Stats: Educating teachers

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Renette J. Blignaut

2013-02-01

Full Text Available The inadequate nature of the education infrastructure in South Africa has led to poor academic performance at public schools. Problems within schools such as under-qualified teachers and poor teacher performance arise due to the poorly constructed education system in our country. The implementation in 2012 of the Curriculum and Assessment Policy Statement (CAPS at public schools in South Africa saw the further crippling of some teachers, as they were unfamiliar with parts of the CAPS subject content. The Statistics and Population Studies department at the University of the Western Cape was asked to join the Maths4Stats project in 2012. This project was launched by Statistics South Africa in an effort to assist in training the teachers in statistical content within the CAPS Mathematics curricula. The University of the Western Cape’s team would like to share their experience of being part of the Maths4Stats training in the Western Cape. This article focuses on how the training sessions were planned and what the outcomes were. With the knowledge gained from our first Maths4Stats experience, it is recommended that future interventions are still needed to ensure that mathematics teachers become well-informed and confident to teach topics such as data handling, probability and regression analysis.

STAT signaling in mammary gland differentiation, cell survival and tumorigenesis.

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Haricharan, S; Li, Y

2014-01-25

The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programmed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Inhibition of STAT-3 results in radiosensitization of human squamous cell carcinoma

International Nuclear Information System (INIS)

Bonner, James A.; Trummell, Hoa Q.; Willey, Christopher D.; Plants, Brian A.; Raisch, Kevin P.

2009-01-01

Background: Signal transducer and activator of transcription-3 (STAT-3) is a downstream component of the Epidermal Growth Factor Receptor (EGFr) signaling process that may facilitate the resistance of tumor cells to conventional cancer treatments. Studies were performed to determine if inhibition of this downstream protein produces radiosensitization. Methods/Results: A431 cells (human squamous cell carcinoma cells with EGFr overexpression) were found to be sensitized to radiation after treatment with STAT-3 small interfering RNA (siRNA). Therefore, a short hairpin RNA (shRNA) against STAT-3 was designed and cloned into a pBABE vector system modified for shRNA expression. Following transfection, clone 2.1 was selected for further study as it showed a dramatic reduction of STAT-3 protein (and mRNA) when compared to A431 parental cells or a negative control shRNA cell line (transfected with STAT-3 shRNA with 2 base pairs mutated). A431 2.1 showed doubling times of 25-31 h as compared to 18-24 h for the parental cell line. The A431 shRNA knockdown STAT-3 cells A431 were more sensitive to radiation than A431 parental or negative STAT-3 control cells. Conclusion: A431 cells stably transfected with shRNA against STAT-3 resulted in enhanced radiosensitivity. Further work will be necessary to determine whether the inhibition of STAT-3 phosphorylation is a necessary step for the radiosensitization that is induced by the inhibition of EGFr.

Role of STAT3 in Transformation and Drug Resistance in CML

International Nuclear Information System (INIS)

Nair, Rajesh R.; Tolentino, Joel H.; Hazlehurst, Lori A.

2012-01-01

Chronic myeloid leukemia (CML) is initially driven by the bcr–abl fusion oncoprotein. The identification of bcr–abl led to the discovery and rapid translation into the clinic of bcr–abl kinase inhibitors. Although, bcr–abl inhibitors are efficacious, experimental evidence indicates that targeting bcr–abl is not sufficient for elimination of minimal residual disease found within the bone marrow (BM). Experimental evidence indicates that the failure to eliminate the leukemic stem cell contributes to persistent minimal residual disease. Thus curative strategies will likely need to focus on strategies where bcr–abl inhibitors are given in combination with agents that specifically target the leukemic stem cell or the leukemic stem cell niche. One potential target to be exploited is the Janus kinase (JAK)/signal transducers and activators of transcription 3 (STAT3) pathway. Recently using STAT3 conditional knock-out mice it was shown that STAT3 is critical for initiating the disease. Interestingly, in the absence of treatment, STAT3 was not shown to be required for maintenance of the disease, suggesting that STAT3 is required only in the tumor initiating stem cell population (Hoelbl et al., 2010). In the context of the BM microenvironment, STAT3 is activated in a bcr–abl independent manner by the cytokine milieu. Activation of JAK/STAT3 was shown to contribute to cell survival even in the event of complete inhibition of bcr–abl activity within the BM compartment. Taken together, these studies suggest that JAK/STAT3 is an attractive therapeutic target for developing strategies for targeting the JAK–STAT3 pathway in combination with bcr–abl kinase inhibitors and may represent a viable strategy for eliminating or reducing minimal residual disease located in the BM in CML.

Role of STAT3 in Transformation and Drug Resistance in CML

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Nair, Rajesh R.; Tolentino, Joel H.; Hazlehurst, Lori A., E-mail: lori.hazlehurst@moffitt.org [Molecular Oncology Program, H. Lee Moffitt Cancer Center, Tampa, FL (United States)

2012-04-10

Chronic myeloid leukemia (CML) is initially driven by the bcr–abl fusion oncoprotein. The identification of bcr–abl led to the discovery and rapid translation into the clinic of bcr–abl kinase inhibitors. Although, bcr–abl inhibitors are efficacious, experimental evidence indicates that targeting bcr–abl is not sufficient for elimination of minimal residual disease found within the bone marrow (BM). Experimental evidence indicates that the failure to eliminate the leukemic stem cell contributes to persistent minimal residual disease. Thus curative strategies will likely need to focus on strategies where bcr–abl inhibitors are given in combination with agents that specifically target the leukemic stem cell or the leukemic stem cell niche. One potential target to be exploited is the Janus kinase (JAK)/signal transducers and activators of transcription 3 (STAT3) pathway. Recently using STAT3 conditional knock-out mice it was shown that STAT3 is critical for initiating the disease. Interestingly, in the absence of treatment, STAT3 was not shown to be required for maintenance of the disease, suggesting that STAT3 is required only in the tumor initiating stem cell population (Hoelbl et al., 2010). In the context of the BM microenvironment, STAT3 is activated in a bcr–abl independent manner by the cytokine milieu. Activation of JAK/STAT3 was shown to contribute to cell survival even in the event of complete inhibition of bcr–abl activity within the BM compartment. Taken together, these studies suggest that JAK/STAT3 is an attractive therapeutic target for developing strategies for targeting the JAK–STAT3 pathway in combination with bcr–abl kinase inhibitors and may represent a viable strategy for eliminating or reducing minimal residual disease located in the BM in CML.

The Multifaceted Roles of STAT3 Signaling in the Progression of Prostate Cancer

International Nuclear Information System (INIS)

Bishop, Jennifer L.; Thaper, Daksh; Zoubeidi, Amina

2014-01-01

The signal transducer and activator of transcription (STAT)3 governs essential functions of epithelial and hematopoietic cells that are often dysregulated in cancer. While the role for STAT3 in promoting the progression of many solid and hematopoietic malignancies is well established, this review will focus on the importance of STAT3 in prostate cancer progression to the incurable metastatic castration-resistant prostate cancer (mCRPC). Indeed, STAT3 integrates different signaling pathways involved in the reactivation of androgen receptor pathway, stem like cells and the epithelial to mesenchymal transition that drive progression to mCRPC. As equally important, STAT3 regulates interactions between tumor cells and the microenvironment as well as immune cell activation. This makes it a major factor in facilitating prostate cancer escape from detection of the immune response, promoting an immunosuppressive environment that allows growth and metastasis. Based on the multifaceted nature of STAT3 signaling in the progression to mCRPC, the promise of STAT3 as a therapeutic target to prevent prostate cancer progression and the variety of STAT3 inhibitors used in cancer therapies is discussed

Stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner

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Chih-I Tai

2014-09-01

Full Text Available Stat3 is essential for mouse embryonic stem cell (mESC self-renewal mediated by LIF/gp130 receptor signaling. Current understanding of Stat3-mediated ESC self-renewal mechanisms is very limited, and has heretofore been dominated by the view that Stat3 signaling functions in a binary “on/off” manner. Here, in contrast to this binary viewpoint, we demonstrate a contextual, rheostat-like mechanism for Stat3's function in mESCs. Activation and expression levels determine whether Stat3 functions in a self-renewal or a differentiation role in mESCs. We also show that Stat3 induces rapid differentiation of mESCs toward the trophectoderm (TE lineage when its activation level exceeds certain thresholds. Stat3 induces this differentiation phenotype via induction of Tfap2c and its downstream target Cdx2. Our findings provide a novel concept in the realm of Stat3, self-renewal signaling, and pluripotent stem cell biology. Ultimately, this finding may facilitate the development of conditions for the establishment of authentic non-rodent ESCs.

STAT3 in the systemic inflammation of cancer cachexia.

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Zimmers, Teresa A; Fishel, Melissa L; Bonetto, Andrea

2016-06-01

Weight loss is diagnostic of cachexia, a debilitating syndrome contributing mightily to morbidity and mortality in cancer. Most research has probed mechanisms leading to muscle atrophy and adipose wasting in cachexia; however cachexia is a truly systemic phenomenon. Presence of the tumor elicits an inflammatory response and profound metabolic derangements involving not only muscle and fat, but also the hypothalamus, liver, heart, blood, spleen and likely other organs. This global response is orchestrated in part through circulating cytokines that rise in conditions of cachexia. Exogenous Interleukin-6 (IL6) and related cytokines can induce most cachexia symptomatology, including muscle and fat wasting, the acute phase response and anemia, while IL-6 inhibition reduces muscle loss in cancer. Although mechanistic studies are ongoing, certain of these cachexia phenotypes have been causally linked to the cytokine-activated transcription factor, STAT3, including skeletal muscle wasting, cardiac dysfunction and hypothalamic inflammation. Correlative studies implicate STAT3 in fat wasting and the acute phase response in cancer cachexia. Parallel data in non-cancer models and disease states suggest both pathological and protective functions for STAT3 in other organs during cachexia. STAT3 also contributes to cancer cachexia through enhancing tumorigenesis, metastasis and immune suppression, particularly in tumors associated with high prevalence of cachexia. This review examines the evidence linking STAT3 to multi-organ manifestations of cachexia and the potential and perils for targeting STAT3 to reduce cachexia and prolong survival in cancer patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of novel small molecules that inhibit STAT3-dependent transcription and function.

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Iryna Kolosenko

Full Text Available Activation of Signal Transducer and Activator of Transcription 3 (STAT3 has been linked to several processes that are critical for oncogenic transformation, cancer progression, cancer cell proliferation, survival, drug resistance and metastasis. Inhibition of STAT3 signaling has shown a striking ability to inhibit cancer cell growth and therefore, STAT3 has become a promising target for anti-cancer drug development. The aim of this study was to identify novel inhibitors of STAT-dependent gene transcription. A cellular reporter-based system for monitoring STAT3 transcriptional activity was developed which was suitable for high-throughput screening (Z' = 0,8. This system was used to screen a library of 28,000 compounds (the ENAMINE Drug-Like Diversity Set. Following counter-screenings and toxicity studies, we identified four hit compounds that were subjected to detailed biological characterization. Of the four hits, KI16 stood out as the most promising compound, inhibiting STAT3 phosphorylation and transcriptional activity in response to IL6 stimulation. In silico docking studies showed that KI16 had favorable interactions with the STAT3 SH2 domain, however, no inhibitory activity could be observed in the STAT3 fluorescence polarization assay. KI16 inhibited cell viability preferentially in STAT3-dependent cell lines. Taken together, using a targeted, cell-based approach, novel inhibitors of STAT-driven transcriptional activity were discovered which are interesting leads to pursue further for the development of anti-cancer therapeutic agents.

Inhibition of STAT3 Expression and Signaling in Resveratrol-Differentiated Medulloblastoma Cells

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Li-Jun Yu

2008-07-01

Full Text Available In this study, the potential influence of resveratrol (3,5,4′-trihydroxy-trans-stilbene in signal transducer and activator of transcription 3 (STAT3 signaling of medulloblastoma cells was evaluated by checking the status of STAT3 signaling and its downstream gene expression in two medulloblastoma cell lines (UW228-2 and UW228-3 with and without resveratrol treatment. The results revealed that resveratrol induced neuronal differentiation of medulloblastoma cells. Signal transducer and activator of transcription 3 expression and phosphorylation were detected in normally cultured UW228-2 and UW228-3 cells that were apparently attenuated after resveratrol treatment. The expression of STAT3 downstream genes, survivin, cyclin D1, Cox-2, and c-Myc, was suppressed but Bcl-2 was enhanced by resveratrol. Meanwhile, the production and secretion of leukemia inhibitory factor, a STAT3 activator, became active in resveratrol-treated cells. To further ascertain the significance of STAT3 signaling for medulloblastoma cells, AG490, a selective inhibitor of STAT3 phosphorylation, was used to treat UW228-3 cells. Phosphorylation of STAT3 was inhibited by AG490 accompanied with growth suppression, differentiation-like changes, and down-regulation of survivin, cyclin D1, Cox-2, and c-Myc. Our data thus suggest the importance of STAT3 signaling in maintenance and survival of medulloblastoma cells. This signaling may be the major target of resveratrol. Enhanced leukemia inhibitory factor and Bcl-2 expressions in resveratrol-treated cells might reflect a compensatory response to the loss of STAT3 function.

Molecular cloning and expression analysis of the STAT1 gene from olive flounder, Paralichthys olivaceus

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Chung Jongkyeong

2008-06-01

Full Text Available Abstract Background Signal transducer and activator of transcription 1 (STAT1 is a critical component of interferon (IFN-alpha/beta and IFN-gamma signaling. Although seven isoforms of STAT proteins have been reported from mammals, limited information is available for the STAT genes in fish. We isolated complementary DNA with high similarity to mammalian STAT1 from the olive flounder, Paralichthys olivaceus. Results A DNA fragment containing the conserved SH2 domain was amplified by RT-PCR using degenerate primers designed based on the highly conserved sequences in the SH2 domains of the zebrafish and mammalian STAT1. The complete cDNA sequence was obtained by 5' and 3' RACE. The flounder STAT1 transcript consisted of 2,909 bp that encoded a polypeptide of 749 amino acids. The overall similarity between flounder STAT1 and other STATs was very high, with the highest amino acid sequence identity to snakehead (89%. Phylogenetic analyses reveal that flounder STAT1 is in the same monophyletic group with snakehead STAT1. Quantitative real time RT-PCR and in situ hybridization revealed that STAT1 was expressed in almost all examined organs and tissues, with high expression in gill, spleen, kidney, and heart. The accumulation of STAT1 mRNA in different developmental stages, as determined by real time RT-PCR, increased with development. Conclusion Recent cloning of various cytokine genes and the STAT1 gene of olive flounder here suggest that fish also use the highly specialized JAK-STAT pathway for cytokine signaling. Identification of other STAT genes will elucidate in detail the signal transduction system in this fish.

mPGES-1-derived prostaglandin E2 stimulates Stat3 to promote podocyte apoptosis.

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Yu, Jing; Wu, Yimei; Wang, Lu; Zhang, Wen; Xu, Man; Song, Jiayu; Fu, Yu; Cui, Yiyun; Gong, Wei; Li, Shuzhen; Xia, Weiwei; Huang, Songming; Zhang, Aihua; Jia, Zhanjun

2017-11-01

We previously reported that microsomal prostaglandin E synthase-1 (mPGES-1) contributed to adriamycin (Adr)-induced podocyte apoptosis. However, the molecular mechanism remains unclear. Here we studied the role of mPGES-1/PGE2 cascade in activating Stat3 signaling and the contribution of Stat3 in PGE2- and Adr-induced podocyte apoptosis. In murine podocytes, PGE2 dose- and time-dependently increased the phosphorylation of Stat3 in line with the enhanced cell apoptosis and reduced podocyte protein podocin. In agreement with the increased Stat3 phosphorylation, Stat3-derived cytokines including IL-6, IL-17, MCP-1, and ICAM-1 were significantly upregulated following PGE2 treatment. By application of a specific Stat3 inhibitor S3I-201, PGE2-induced podocyte apoptosis was largely abolished in parallel with a blockade of podocin reduction. Next, we observed that Adr treatment also enhanced p-Stat3 and activated mPGES-1/PGE2 cascade. Blockade of Stat3 by S3I-201 significantly ameliorated Adr-induced cell apoptosis and podocin reduction. More interestingly, silencing mPGES-1 in podocytes by mPGES-1 siRNA blocked Adr-induced increments of Stat-3 phosphorylation, PGE2 production, and Stat3-derived inflammatory cytokines. Taken together, this study suggested that mPGES-1-derived PGE2 could activate Stat3 signaling to promote podocyte apoptosis. Targeting mPGES-1/PGE2/Stat3 signaling might be a potential strategy for the treatment of podocytopathy.

Evaluation of STAT medication ordering process in a community hospital.

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Abdelaziz, Hani; Richardson, Sandra; Walsh, Kim; Nodzon, Jessica; Schwartz, Barbara

2016-01-01

In most health care facilities, problems related to delays in STAT medication order processing time are of common concern. The purpose of this study was to evaluate processing time for STAT orders at Kimball Medical Center. All STAT orders were reviewed to determine processing time; order processing time was also stratified by physician order entry (physician entered (PE) orders vs. non-physician entered (NPE) orders). Collected data included medication ordered, indication, time ordered, time verified by pharmacist, time sent from pharmacy, and time charted as given to the patient. A total of 502 STAT orders were reviewed and 389 orders were included for analysis. Overall, median time was 29 minutes, IQR 16-63; porder processing time may be improved by increasing the availability of medications in ADM, and pharmacy involvement in the verification process.

PCBP2 enhances the antiviral activity of IFN-α against HCV by stabilizing the mRNA of STAT1 and STAT2.

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Zhongshuai Xin

Full Text Available Interferon-α (IFN-α is a natural choice for the treatment of hepatitis C, but half of the chronically infected individuals do not achieve sustained clearance of hepatitis C virus (HCV during treatment with IFN-α alone. The virus can impair IFN-α signaling and cellular factors that have an effect on the viral life cycles. We found that the protein PCBP2 is down-regulated in HCV-replicon containing cells (R1b. However, the effects and mechanisms of PCBP2 on HCV are unclear. To determine the effect of PCBP2 on HCV, overexpression and knockdown of PCBP2 were performed in R1b cells. Interestingly, we found that PCBP2 can facilitate the antiviral activity of IFN-α against HCV, although the RNA level of HCV was unaffected by either the overexpression or absence of PCBP2 in R1b cells. RIP-qRT-PCR and RNA half-life further revealed that PCBP2 stabilizes the mRNA of STAT1 and STAT2 through binding the 3'Untranslated Region (UTR of these two molecules, which are pivotal for the IFN-α anti-HCV effect. RNA pull-down assay confirmed that there were binding sites located in the C-rich tracts in the 3'UTR of their mRNAs. Stabilization of mRNA by PCBP2 leads to the increased protein expression of STAT1 and STAT2 and a consistent increase of phosphorylated STAT1 and STAT2. These effects, in turn, enhance the antiviral effect of IFN-α. These findings indicate that PCBP2 may play an important role in the IFN-α response against HCV and may benefit the HCV clinical therapy.

Cellular response to alkylating agent MNNG is impaired in STAT1-deficients cells.

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Ah-Koon, Laurent; Lesage, Denis; Lemadre, Elodie; Souissi, Inès; Fagard, Remi; Varin-Blank, Nadine; Fabre, Emmanuelle E; Schischmanoff, Olivier

2016-10-01

The SN 1 alkylating agents activate the mismatch repair system leading to delayed G2 /M cell cycle arrest and DNA repair with subsequent survival or cell death. STAT1, an anti-proliferative and pro-apoptotic transcription factor is known to potentiate p53 and to affect DNA-damage cellular response. We studied whether STAT1 may modulate cell fate following activation of the mismatch repair system upon exposure to the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Using STAT1-proficient or -deficient cell lines, we found that STAT1 is required for: (i) reduction in the extent of DNA lesions, (ii) rapid phosphorylation of T68-CHK2 and of S15-p53, (iii) progression through the G2 /M checkpoint and (iv) long-term survival following treatment with MNNG. Presence of STAT1 is critical for the formation of a p53-DNA complex comprising: STAT1, c-Abl and MLH1 following exposure to MNNG. Importantly, presence of STAT1 allows recruitment of c-Abl to p53-DNA complex and links c-Abl tyrosine kinase activity to MNNG-toxicity. Thus, our data highlight the important modulatory role of STAT1 in the signalling pathway activated by the mismatch repair system. This ability of STAT1 to favour resistance to MNNG indicates the targeting of STAT1 pathway as a therapeutic option for enhancing the efficacy of SN1 alkylating agent-based chemotherapy. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Knockdown of stat3 expression by RNAi inhibits in vitro growth of human ovarian cancer

International Nuclear Information System (INIS)

Zhao, Shu-Hua; Zhao, Fan; Zheng, Jing-Ying; Gao, Li-Fang; Zhao, Xue-Jian; Cui, Man-Hua

2011-01-01

The aim of the study was to investigate the suppressive effects of pSilencer2.1-U6-siRNA-stat3 recombinant plasmids on the growth of ovarian cancer in vitro. Three pairs of DNA template (stat3-1, stat3-2, stat3-3) specific for different target sites on stat3 mRNA were synthesized to reconstruct pSilencer2.1-U6-siRNA-stat3s, which were transfected into SKOV3 cells. The expressions of STAT3, BcL-2, cyclin D1 and C-myc in these cells were detected by Western blot and Northern blot. The cell cycle and the growth were determined by flow cytometry (FCM) and MTT assay, respectively. Cell apoptosis was determined by TUNEL staining. Of the three siRNAs, only siRNA targeting stat3-3 markedly suppressed the protein expression of stat3 in SKOV3 cells; MTT assay and FCM showed that transfection of stat3-3 siRNA could significantly suppress the growth of SKOV3 cells and arrest the cell cycle in vitro. TUNEL staining also showed massive apoptosis in SKOV3 cells transfected with stat3-3 siRNA. pSilencer2.1-U6-siRNA-stat3-3 can significantly inhibit the STAT3 expression in human ovarian cancer cells resulting in the inhibition of the cancer growth and the increase of apoptosis of cancer cells

The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling.

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Carina Michl

Full Text Available Sulforaphane (SFN and moringin (GMG-ITC are edible isothiocyanates present as glucosinolate precursors in cruciferous vegetables and in the plant Moringa oleifera respectively, and recognized for their chemopreventive and medicinal properties. In contrast to the well-studied SFN, little is known about the molecular pathways targeted by GMG-ITC. We investigated the ability of GMG-ITC to inhibit essential signaling pathways that are frequently upregulated in cancer and immune disorders, such as JAK/STAT and NF-κB. We report for the first time that, similarly to SFN, GMG-ITC in the nanomolar range suppresses IL-3-induced expression of STAT5 target genes. GMG-ITC, like SFN, does not inhibit STAT5 phosphorylation, suggesting a downstream inhibitory event. Interestingly, treatment with GMG-ITC or SFN had a limited inhibitory effect on IFNα-induced STAT1 and STAT2 activity, indicating that both isothiocyanates differentially target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar range is a more potent inhibitor of TNF-induced NF-κB activity than SFN. Finally, using a cellular system mimicking constitutive active STAT5-induced cell transformation, we demonstrated that SFN can reverse the survival and growth advantage mediated by oncogenic STAT5 and triggers cell death, therefore providing experimental evidence of a cancer chemopreventive activity of SFN. This work thus identified STAT5, and to a lesser extent STAT1/STAT2, as novel targets of moringin. It also contributes to a better understanding of the biological activities of the dietary isothiocyanates GMG-ITC and SFN and further supports their apparent beneficial role in the prevention of chronic illnesses such as cancer, inflammatory diseases and immune disorders.

STAT FAQs Part 2: Lifetime of PV Panels | State, Local, and Tribal

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Governments | NREL STAT FAQs Part 2: Lifetime of PV Panels STAT FAQs Part 2: Lifetime of PV Panels April 23, 2018 by Benjamin Mow The Solar Technical Assistance Team (STAT) receives many is the productive lifetime and degradation rate of solar PV panels. Question: What is the productive

Stat3 inhibition attenuates mechanical allodynia through transcriptional regulation of chemokine expression in spinal astrocytes.

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Xiaodong Liu

Full Text Available BACKGROUND: Signal transducer and activator of transcription 3 (Stat3 is known to induce cell proliferation and inflammation by regulating gene transcription. Recent studies showed that Stat3 modulates nociceptive transmission by reducing spinal astrocyte proliferation. However, it is unclear whether Stat3 also contributes to the modulation of nociceptive transmission by regulating inflammatory response in spinal astrocytes. This study aimed at investigating the role of Stat3 on neuroinflammation during development of pain in rats after intrathecal injection of lipopolysaccharide (LPS. METHODS: Stat3 specific siRNA oligo and synthetic selective inhibitor (Stattic were applied to block the activity of Stat3 in primary astrocytes or rat spinal cord, respectively. LPS was used to induce the expression of proinflammatory genes in all studies. Immunofluorescence staining of cells and slices of spinal cord was performed to monitor Stat3 activation. The impact of Stat3 inhibition on proinflammatory genes expression was determined by cytokine antibody array, enzyme-linked immunosorbent assay and real-time polymerase chain reaction. Mechanical allodynia, as determined by the threshold pressure that could induce hind paw withdrawal after application of standardized von Frey filaments, was used to detect the effects of Stat3 inhibition after pain development with intrathecal LPS injection. RESULTS: Intrathecal injection of LPS activated Stat3 in reactive spinal astrocytes. Blockade of Stat3 activity attenuated mechanical allodynia significantly and was correlated with a lower number of reactive astrocytes in the spinal dorsal horn. In vitro study demonstrated that Stat3 modulated inflammatory response in primary astrocytes by transcriptional regulation of chemokine expression including Cx3cl1, Cxcl5, Cxcl10 and Ccl20. Similarly, inhibition of Stat3 reversed the expression of these chemokines in the spinal dorsal horn. CONCLUSIONS: Stat3 acted as a

Constitutive STAT5 Activation Correlates With Better Survival in Cervical Cancer Patients Treated With Radiation Therapy

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Chen, Helen H.W. [Department of Radiation Oncology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Chou, Cheng-Yang [Department of Obstetrics and Gynecology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Wu, Yuan-Hua; Hsueh, Wei-Ting; Hsu, Chiung-Hui [Department of Radiation Oncology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Guo, How-Ran [Department of Environmental and Occupational Health, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Lee, Wen-Ying, E-mail: 7707@so-net.net.tw [Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan (China) and Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Su, Wu-Chou, E-mail: sunnysu@mail.ncku.edu.tw [Department of Internal Medicine, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China)

2012-02-01

Purpose: Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3, and STAT5, have been detected in a wide variety of human primary tumors and have been demonstrated to directly contribute to oncogenesis. However, the expression pattern of these STATs in cervical carcinoma is still unknown, as is whether or not they have prognostic significance. This study investigated the expression patterns of STAT1, STAT3, and STAT5 in cervical cancer and their associations with clinical outcomes in patients treated with radical radiation therapy. Methods and Materials: A total of 165 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) Stages IB to IVA cervical cancer underwent radical radiation therapy, including external beam and/or high-dose-rate brachytherapy between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and to evaluate the effects of these factors affecting patient survival. Results: Constitutive activations of STAT1, STAT3, and STAT5 were observed in 11%, 22%, and 61% of the participants, respectively. While STAT5 activation was associated with significantly better metastasis-free survival (p < 0.01) and overall survival (p = 0.04), STAT1 and STAT3 activation were not. Multivariate analyses showed that STAT5 activation, bulky tumor ({>=}4 cm), advanced stage (FIGO Stages III and IV), and brachytherapy (yes vs. no) were independent prognostic factors for cause-specific overall survival. None of the STATs was associated with local relapse. STAT5 activation (odds ratio = 0.29, 95% confidence interval = 0.13-0.63) and advanced stage (odds ratio = 2.54; 95% confidence interval = 1.03-6.26) were independent predictors of distant metastasis. Conclusions: This is the first report to provide the overall expression patterns and prognostic significance of

FastStats: Illegal Drug Use

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Interleukin-2 induces tyrosine phosphorylation and nuclear translocation of stat3 in human T lymphocytes

DEFF Research Database (Denmark)

Nielsen, M; Svejgaard, A; Skov, S

1994-01-01

that stimulation through the IL-2R induced tyrosine phosphorylation and subsequent nuclear translocation of stat3, a newly identified member of the signal transducers and activators of transcription (STAT) family of proteins. In contrast, stat1 proteins were not tyrosine phosphorylated after IL-2 ligation, whereas...... an apparent molecular mass of 84 kDa and was not recognized by stat3 or stat1 mAb or antisera. Since IL-2 induced nuclear translocation of the 84 kDa protein and stat3 followed identical kinetics, p84 is a candidate for a new, yet undefined, member of the STAT family. Taken together, we report that IL-2...... induces tyrosine phosphorylation and subsequent nuclear translocation of stat3 and an as yet undefined 84-kDa protein in antigen-specific human T cell lines....

Rac1 promotes chondrogenesis by regulating STAT3 signaling pathway.

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Kim, Hyoin; Sonn, Jong Kyung

2016-09-01

The small GTPase protein Rac1 is involved in a wide range of biological processes including cell differentiation. Previously, Rac1 was shown to promote chondrogenesis in micromass cultures of limb mesenchyme. However, the pathways mediating Rac1's role in chondrogenesis are not fully understood. This study aimed to explore the molecular mechanisms by which Rac1 regulates chondrogenic differentiation. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) was increased as chondrogenesis proceeded in micromass cultures of chick wing bud mesenchyme. Inhibition of Rac1 with NSC23766, janus kinase 2 (JAK2) with AG490, or STAT3 with stattic inhibited chondrogenesis and reduced phosphorylation of STAT3. Conversely, overexpression of constitutively active Rac1 (Rac L61) increased phosphorylation of STAT3. Rac L61 expression resulted in increased expression of interleukin 6 (IL-6), and treatment with IL-6 increased phosphorylation of STAT3. NSC23766, AG490, and stattic prohibited cell aggregation, whereas expression of Rac L61 increased cell aggregation, which was reduced by stattic treatment. Our studies indicate that Rac1 induces STAT3 activation through expression and action of IL-6. Overexpression of Rac L61 increased expression of bone morphogenic protein 4 (BMP4). BMP4 promoted chondrogenesis, which was inhibited by K02288, an activin receptor-like kinase-2 inhibitor, and increased phosphorylation of p38 MAP kinase. Overexpression of Rac L61 also increased phosphorylation of p38 MAPK, which was reduced by K02288. These results suggest that Rac1 activates STAT3 by expression of IL-6, which in turn increases expression and activity of BMP4, leading to the promotion of chondrogenesis. © 2016 International Federation for Cell Biology.

AC/TiO2/Rubber Composite Sheet Catalysts; Fabrication, Characterization and Photocatalytic Activities

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Sriwong Chaval

2015-01-01

Full Text Available The AC/TiO2/Rubber (ACTR composite sheets weresuccessfully fabricated by a simply mixing of fixed TiO2 suspension and natural rubber latex (60% HA contents withthe varyingamounts of activated carbon (AC suspension, followed by stirring, pouring into apetri dish mold, drying at room temperature (RT, after that taking out from a mold, reversing and drying again at RT. Then, the as-fabricated ACTR composite sheets were characterized by X-ray diffractometer (XRD, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR, energy dispersive X-ray spectroscopy (EDS and scanning electron microscopy (SEMtechniques. The photocatalytic efficiencies of all ACTR composite sheet samples were evaluated by photo degrading of methylene blue (MB dye solution under UV light irradiation. The results showed that the photocatalytic activity of ACTR sheet with10.0wt%AC loading has the highest efficiency for the photo degradation of MB dye than the other sheets. This is due to the fact that it is relatively with the synergistic effect of well-combined titanium dioxide catalyst and activated carbon adsorbent.

FastStats: A to Z

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Identification, gene expression and immune function of the novel Bm-STAT gene in virus-infected Bombyx mori.

Science.gov (United States)

Zhang, Xiaoli; Guo, Rui; Kumar, Dhiraj; Ma, Huanyan; Liu, Jiabin; Hu, Xiaolong; Cao, Guangli; Xue, Renyu; Gong, Chengliang

2016-02-10

Genes in the signal transducer and activator of transcription (STAT) family are vital for activities including gene expression and immune response. To investigate the functions of the silkworm Bombyx mori STAT (Bm-STAT) gene in antiviral immunity, two Bm-STAT gene isoforms, Bm-STAT-L for long form and Bm-STAT-S for short form, were cloned. Sequencing showed that the open reading frames were 2313 bp encoding 770 amino acid residues for Bm-STAT-L and 2202 bp encoding 734 amino acid residues for Bm-STAT-S. The C-terminal 42 amino acid residues of Bm-STAT-L were different from the last 7 amino acid residues of Bm-STAT-S. Immunofluorescence showed that Bm-STAT was primarily distributed in the nucleus. Transcription levels of Bm-STAT in different tissues were determined by quantitative PCR, and the results revealed Bm-STAT was mainly expressed in testes. Western blots showed two bands with molecular weights of 70 kDa and 130 kDa in testes, but no bands were detected in ovaries by using anti-Bm-STAT antibody as the primary antibody. Expression of Bm-STAT in hemolymph at 48 h post infection with B. mori macula-like virus (BmMLV) was slightly enhanced compared with controls, suggesting a weak response induced by infection with BmMLV. Hemocyte immunofluorescence showed that Bm-STAT expression was elevated in B. mori nucleopolyhedrovirus (BmNPV)-infected cells. Moreover, resistance of BmN cells to BmNPV was reduced by downregulation of Bm-STAT expression and increased by upregulation. Resistance of BmN cells to BmCPV was not significantly improved by upregulating Bm-STAT expression. Therefore, we concluded that Bm-STAT is a newly identified insect gene of the STAT family. The JAK-STAT pathway has a more specialized role in antiviral defense in silkworms, but JAK-STAT pathway is not triggered in response to all viruses. Copyright © 2015 Elsevier B.V. All rights reserved.

Activated STAT5 Confers Resistance to Intestinal Injury by Increasing Intestinal Stem Cell Proliferation and Regeneration

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Shila Gilbert

2015-02-01

Full Text Available Intestinal epithelial stem cells (IESCs control the intestinal homeostatic response to inflammation and regeneration. The underlying mechanisms are unclear. Cytokine-STAT5 signaling regulates intestinal epithelial homeostasis and responses to injury. We link STAT5 signaling to IESC replenishment upon injury by depletion or activation of Stat5 transcription factor. We found that depletion of Stat5 led to deregulation of IESC marker expression and decreased LGR5+ IESC proliferation. STAT5-deficient mice exhibited worse intestinal histology and impaired crypt regeneration after γ-irradiation. We generated a transgenic mouse model with inducible expression of constitutively active Stat5. In contrast to Stat5 depletion, activation of STAT5 increased IESC proliferation, accelerated crypt regeneration, and conferred resistance to intestinal injury. Furthermore, ectopic activation of STAT5 in mouse or human stem cells promoted LGR5+ IESC self-renewal. Accordingly, STAT5 promotes IESC proliferation and regeneration to mitigate intestinal inflammation. STAT5 is a functional therapeutic target to improve the IESC regenerative response to gut injury.

MSM enhances GH signaling via the Jak2/STAT5b pathway in osteoblast-like cells and osteoblast differentiation through the activation of STAT5b in MSCs.

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Youn Hee Joung

Full Text Available Methylsulfonylmethane (MSM is a naturally occurring sulfur compound with well-known anti-oxidant properties and anti-inflammatory activities. But, its effects on bone are unknown. Growth hormone (GH is regulator of bone growth and bone metabolism. GH activates several signaling pathways such as the Janus kinase (Jak/signal transducers and activators of transcription (STAT pathway, thereby regulating expression of genes including insulin-like growth factor (IGF-1. GH exerts effects both directly and via IGF-1, which signals by activating the IGF-1 receptor (IGF-1R. In this study, we investigated the effects of MSM on the GH signaling via the Jak/STAT pathway in osteoblasts and the differentiation of primary bone marrow mesenchymal stem cells (MSCs. MSM was not toxic to osteoblastic cells and MSCs. MSM increased the expression of GH-related proteins including IGF-1R, p-IGF-1R, STAT5b, p-STAT5b, and Jak2 in osteoblastic cells and MSCs. MSM increased IGF-1R and GHR mRNA expression in osteoblastic cells. The expression of MSM-induced IGF-1R and GHR was inhibited by AG490, a Jak2 kinase inhibitor. MSM induced binding of STAT5 to the IGF-1R and increased IGF-1 and IGF-1R promoter activities. Analysis of cell extracts by immunoprecipitation and Western blot showed that MSM enhanced GH-induced activation of Jak2/STAT5b. We found that MSM and GH, separately or in combination, activated GH signaling via the Jak2/STAT5b pathway in UMR-106 cells. Using siRNA analysis, we found that STAT5b plays an essential role in GH signaling activation in C3H10T1/2 cells. Osteogenic marker genes (ALP, ON, OCN, BSP, OSX, and Runx2 were activated by MSM, and siRNA-mediated STAT5b knockdown inhibited MSM-induced expression of osteogenic markers. Furthermore, MSM increased ALP activity and the mineralization of MSCs. Taken together, these results indicated that MSM can promote osteogenic differentiation of MSCs through activation of STAT5b.

Opposing roles of STAT4 and Dnmt3a in Th1 gene regulation

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Pham, Duy; Yu, Qing; Walline, Crystal C.; Muthukrishnan, Rajarajeswari; Blum, Janice S.; Kaplan, Mark H.

2013-01-01

The Signal Transducer and Activator of Transcription factor STAT4 is a critical regulator of Th1 differentiation and inflammatory disease. Yet, how STAT4 regulates gene expression is still unclear. In this report, we define a STAT4-dependent sequence of events including H3K4 methylation, Jmjd3 association with STAT4 target loci, and a Jmjd3-dependent decrease in H3K27 trimethylation and DNA methyltransferase (Dnmt) 3a association with STAT4 target loci. Dnmt3a has an obligate role in repressing Th1 gene expression, and in Th1 cultures deficient in both STAT4 and Dnmt3a, there is recovery in the expression of a subset of Th1 genes that is sufficient to increase IFNγ production. Moreover, although STAT4-deficient mice are protected from the development of EAE, mice deficient in STAT4 and conditionally-deficient in Dnmt3a in T cells develop paralysis. Th1 genes that are de-repressed in the absence of Dnmt3a have greater induction following the ectopic expression of the Th1-associated transcription factors T-bet and Hlx1. Together, these data demonstrate that STAT4 and Dnmt3a play opposing roles in regulating Th1 gene expression, and that one mechanism for STAT4-dependent gene programming is in establishing a de-repressed genetic state susceptible to transactivation by additional fate-determining transcription factors. PMID:23772023

Canonical and Non-Canonical Aspects of JAK-STAT Signaling: Lessons from Interferons for Cytokine Responses.

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Majoros, Andrea; Platanitis, Ekaterini; Kernbauer-Hölzl, Elisabeth; Rosebrock, Felix; Müller, Mathias; Decker, Thomas

2017-01-01

Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. In recent years, several deviations from this paradigm were reported. These include kinase-independent JAK functions as well as extra- and intranuclear activities of U-STATs without phosphotyrosines. Additionally, transcriptional control by STAT complexes resembling neither GAF nor ISGF3 contributes to transcriptome changes in IFN-treated cells. Our review summarizes the contribution of non-canonical JAK-STAT signaling to the innate antimicrobial immunity imparted by IFN. Moreover, we touch upon functions of IFN pathway proteins beyond the IFN response. These include metabolic functions of IRF9 as well as the regulation of natural killer cell activity by kinase-dead TYK2 and different phosphorylation isoforms of STAT1.

Differences in antiproliferative effect of STAT3 inhibition in HCC cells with versus without HBV expression

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Hong, Yun; Zhou, Lin; Xie, Haiyang; Wang, Weilin; Zheng, Shusen

2015-01-01

Chronic infection with hepatitis B virus (HBV) plays an important role in the etiology of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 3 (STAT3) inactivation could inhibit the tumor growth of HCC. In this study, differential antiproliferative effect of STAT3 inhibition was observed with HBV-related HCC cells being more resistant than non-HBV-related HCC cells. Resistance of HBV-related HCC cells to STAT3 inhibition was positively correlated to the expression of HBV. Enhanced ERK activation after STAT3 blockade was detected in HBV-related HCC cells but not in non-HBV-related HCC cells. Combined ERK and STAT3 inhibition eliminates the discrepancy between the two types of HCC cells. Moderate reduced HBV expression was found after STAT3 inhibition. These findings disclose a discrepancy in cellular response to STAT3 inhibition between non-HBV-related and HBV-related HCC cells and underscore the complexity of antiproliferative effect of STAT3 inactivation in HBV-related HCC cells. - Highlights: • HBV endows HCC cells with resistance to STAT3 inactivation on proliferation. • Abnormal ERK activation after STAT3 inhibition in HBV-related HCC cells. • Combined ERK and STAT3 inhibition eliminates the discrepancy. • STAT3 inhibition moderately reduces HBV expression

Differences in antiproliferative effect of STAT3 inhibition in HCC cells with versus without HBV expression

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Hong, Yun; Zhou, Lin; Xie, Haiyang; Wang, Weilin [Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou, Zhejiang 310003 (China); Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Qingchun Road 79, Hangzhou, Zhejiang 310003 (China); Zheng, Shusen, E-mail: shusenzheng@zju.edu.cn [Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Qingchun Road 79, Hangzhou, Zhejiang 310003 (China); Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Qingchun Road 79, Hangzhou, Zhejiang 310003 (China)

2015-06-05

Chronic infection with hepatitis B virus (HBV) plays an important role in the etiology of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 3 (STAT3) inactivation could inhibit the tumor growth of HCC. In this study, differential antiproliferative effect of STAT3 inhibition was observed with HBV-related HCC cells being more resistant than non-HBV-related HCC cells. Resistance of HBV-related HCC cells to STAT3 inhibition was positively correlated to the expression of HBV. Enhanced ERK activation after STAT3 blockade was detected in HBV-related HCC cells but not in non-HBV-related HCC cells. Combined ERK and STAT3 inhibition eliminates the discrepancy between the two types of HCC cells. Moderate reduced HBV expression was found after STAT3 inhibition. These findings disclose a discrepancy in cellular response to STAT3 inhibition between non-HBV-related and HBV-related HCC cells and underscore the complexity of antiproliferative effect of STAT3 inactivation in HBV-related HCC cells. - Highlights: • HBV endows HCC cells with resistance to STAT3 inactivation on proliferation. • Abnormal ERK activation after STAT3 inhibition in HBV-related HCC cells. • Combined ERK and STAT3 inhibition eliminates the discrepancy. • STAT3 inhibition moderately reduces HBV expression.

Screening for MPL mutations in essential thrombocythemia and primary myelofibrosis: normal Mpl expression and absence of constitutive STAT3 and STAT5 activation in MPLW515L-positive platelets.

Science.gov (United States)

Glembotsky, Ana C; Korin, Laura; Lev, Paola R; Chazarreta, Carlos D; Marta, Rosana F; Molinas, Felisa C; Heller, Paula G

2010-05-01

To evaluate the frequency of MPL W515L, W515K and S505N mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) and to determine whether MPLW515L leads to impaired Mpl expression, constitutive STAT3 and STAT5 activation and enhanced response to thrombopoietin (TPO). Mutation detection was performed by allele-specific PCR and sequencing. Platelet Mpl expression was evaluated by flow cytometry, immunoblotting and real-time RT-PCR. Activation of STAT3 and STAT5 before and after stimulation with increasing concentrations of TPO was studied by immunoblotting. Plasma TPO was measured by ELISA. MPLW515L was detected in 1 of 100 patients with ET and 1 of 11 with PMF. Platelets from the PMF patient showed 100% mutant allele, which was Mpl surface and total protein expression were normal, and TPO levels were mildly increased in the MPLW515L-positive ET patient, while MPL transcripts did not differ from controls in both MPLW515L-positive patients. Constitutive STAT3 and STAT5 phosphorylation was absent and dose response to TPO-induced phosphorylation was not enhanced. The low frequency of MPL mutations in this cohort is in agreement with previous studies. The finding of normal Mpl levels in MPLW515L-positive platelets indicates this mutation does not lead to dysregulated Mpl expression, as frequently shown for myeloproliferative neoplasms. The lack of spontaneous STAT3 and STAT5 activation and the normal response to TPO is unexpected as MPLW515L leads to constitutive receptor activation and hypersensitivity to TPO in experimental models.

PTP1B is a negative regulator of interleukin 4–induced STAT6 signaling

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Lu, Xiaoqing; Malumbres, Raquel; Shields, Benjamin; Jiang, Xiaoyu; Sarosiek, Kristopher A.; Natkunam, Yasodha

2008-01-01

Protein tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed enzyme shown to negatively regulate multiple tyrosine phosphorylation-dependent signaling pathways. PTP1B can modulate cytokine signaling pathways by dephosphorylating JAK2, TYK2, and STAT5a/b. Herein, we report that phosphorylated STAT6 may serve as a cytoplasmic substrate for PTP1B. Overexpression of PTP1B led to STAT6 dephosphorylation and the suppression of STAT6 transcriptional activity, whereas PTP1B knockdown or deficiency augmented IL-4–induced STAT6 signaling. Pretreatment of these cells with the PTK inhibitor staurosporine led to sustained STAT6 phosphorylation consistent with STAT6 serving as a direct substrate of PTP1B. Furthermore, PTP1B-D181A “substrate-trapping” mutants formed stable complexes with phosphorylated STAT6 in a cellular context and endogenous PTP1B and STAT6 interacted in an interleukin 4 (IL-4)–inducible manner. We delineate a new negative regulatory loop of IL-4–JAK-STAT6 signaling. We demonstrate that IL-4 induces PTP1B mRNA expression in a phosphatidylinositol 3-kinase–dependent manner and enhances PTP1B protein stability to suppress IL-4–induced STAT6 signaling. Finally, we show that PTP1B expression may be preferentially elevated in activated B cell–like diffuse large B-cell lymphomas. These observations identify a novel regulatory loop for the regulation of IL-4–induced STAT6 signaling that may have important implications in both neoplastic and inflammatory processes. PMID:18716132

Evaluation of STAT medication ordering process in a community hospital

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Abdelaziz H

2016-06-01

Full Text Available Background: In most health care facilities, problems related to delays in STAT medication order processing time are of common concern. Objective: The purpose of this study was to evaluate processing time for STAT orders at Kimball Medical Center. Methods: All STAT orders were reviewed to determine processing time; order processing time was also stratified by physician order entry (physician entered (PE orders vs. non-physician entered (NPE orders. Collected data included medication ordered, indication, time ordered, time verified by pharmacist, time sent from pharmacy, and time charted as given to the patient. Results: A total of 502 STAT orders were reviewed and 389 orders were included for analysis. Overall, median time was 29 minutes, IQR 16–63; p<0.0001. . The time needed to process NPE orders was significantly less than that needed for PE orders (median 27 vs. 34 minutes; p=0.026. In terms of NPE orders, the median total time required to process STAT orders for medications available in the Automated Dispensing Devices (ADM was within 30 minutes, while that required to process orders for medications not available in the ADM was significantly greater than 30 minutes. For PE orders, the median total time required to process orders for medications available in the ADM (i.e., not requiring pharmacy involvement was significantly greater than 30 minutes. [Median time = 34 minutes (p<0.001]. Conclusion: We conclude that STAT order processing time may be improved by increasing the availability of medications in ADM, and pharmacy involvement in the verification process.

Withaferin A Inhibits STAT3 and Induces Tumor Cell Death in Neuroblastoma and Multiple Myeloma

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Lisette P. Yco

2014-01-01

Full Text Available Signal transducer and activator of transcription 3 (STAT3 is an oncogenic transcription factor that has been implicated in many human cancers and has emerged as an ideal target for cancer therapy. Withaferin A (WFA is a natural product with promising antiproliferative properties through its association with a number of molecular targets including STAT3. However, the effect of WFA in pediatric neuroblastoma (NB and its interaction with STAT3 have not been reported. In this study, we found that WFA effectively induces dose-dependent cell death in high-risk and drug-resistant NB as well as multiple myeloma (MM tumor cells, prevented interleukin-6 (IL-6–mediated and persistently activated STAT3 phosphorylation at Y705, and blocked the transcriptional activity of STAT3. We further provide computational models that show that WFA binds STAT3 near the Y705 phosphotyrosine residue of the STAT3 Src homology 2 (SH2 domain, suggesting that WFA prevents STAT3 dimer formation similar to BP-1-102, a well-established STAT3 inhibitor. Our findings propose that the antitumor activity of WFA is mediated at least in part through inhibition of STAT3 and provide a rationale for further drug development and clinical use in NB and MM.

Stat3 Expression and Its Correlation with Proliferation and Apoptosis/Autophagy in Gliomas

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Valentina Caldera

2008-01-01

Full Text Available Signal transducer and activator of transcription-3 (Stat3 was studied along with several steps of the PI3/Akt pathway in a series of 64 gliomas that included both malignant and low-grade tumors, using quantitative immunohistochemistry, Western blotting, and molecular biology techniques. The goal of the study was to investigate whether activated Stat3 (phospho-Stat3 levels correlated with cell proliferation, apoptosis, and autophagy. Stat3 and activated Akt (phospho-Akt expression increased with malignancy grade, but did not correlate with proliferation and survival within the category of glioblastomas. A correlation of Stat3 with Akt was found, indicating a regulation of the former by the PI3/Akt pathway, which, in turn, was in relation with EGFR amplification. Stat3 and Akt did not show any correlation with apoptosis, whereas they showed an inverse correlation with Beclin 1, a stimulator of autophagy, which was rarely positive in glioblastomas. Autophagy seems then to be inactivated in malignant gliomas.

Decreased STAT3 Phosphorylation Mediates Cell Swelling in Ammonia-Treated Astrocyte Cultures

Directory of Open Access Journals (Sweden)

Arumugam R. Jayakumar

2016-12-01

Full Text Available Brain edema, due largely to astrocyte swelling, and the subsequent increase in intracranial pressure and brain herniation, are major complications of acute liver failure (ALF. Elevated level of brain ammonia has been strongly implicated in the development of astrocyte swelling associated with ALF. The means by which ammonia brings about astrocyte swelling, however, is incompletely understood. Recently, oxidative/nitrosative stress and associated signaling events, including activation of mitogen-activated protein kinases (MAPKs, as well as activation of the transcription factor, nuclear factor-kappaB (NF-κB, have been implicated in the mechanism of ammonia-induced astrocyte swelling. Since these signaling events are known to be regulated by the transcription factor, signal transducer and activator of transcription 3 (STAT3, we examined the state of STAT3 activation in ammonia-treated cultured astrocytes, and determined whether altered STAT3 activation and/or protein expression contribute to the ammonia-induced astrocyte swelling. STAT3 was found to be dephosphorylated (inactivated at Tyrosine705 in ammonia-treated cultured astrocytes. Total STAT3 protein level was also reduced in ammonia-treated astrocytes. We also found a significant increase in protein tyrosine phosphatase receptor type-1 (PTPRT-1 protein expression in ammonia-treated cultured astrocytes, and that inhibition of PTPRT-1 enhanced the phosphorylation of STAT3 after ammonia treatment. Additionally, exposure of cultured astrocytes to inhibitors of protein tyrosine phosphatases diminished the ammonia-induced cell swelling, while cultured astrocytes over-expressing STAT3 showed a reduction in the astrocyte swelling induced by ammonia. Collectively, these studies strongly suggest that inactivation of STAT3 represents a critical event in the mechanism of the astrocyte swelling associated with acute liver failure.

DemandStat

International Nuclear Information System (INIS)

2003-01-01

DemandStat is an accurate and up-to-date international statistics database dedicated to energy demand, with an unrivaled level of details for powerful market analysis. It provides detailed consumption statistics (30 sectors) on all energies, detailed 2003 data and historical annual data since 1970, frequent data revision and update (2 updates options), 150 data sources gathered and expertized, all data on a single database Consistent and homogeneous statistics, in line with all major data providers (IEA, Eurostat, ADB, OLADE, etc), no ruptures in time-series with easy request building and data analysis and reactive support from data experts. (A.L.B.)

Facts and figures in 2004

International Nuclear Information System (INIS)

Lavergne, R.; Meuric, L.; Scherrer, S.; Paquel, V.; Louati, S.; Thienard, H.

2005-01-01

This document gathers a series of articles dedicated to the situation of the energy sector in France at the end of 2004: -) the energy balance sheet, -) the trend concerning energy consumption since 1973, -) the energy bill, -) figures about electrical power, -) figures about natural gas, -) figures about solid fossil fuels, -) figures about oil, and -) figures about renewable energies. The important fact to note is that the energy bill has soared by 24.1% to reach 28.35 milliard euros which represents 1.75% of the gross national product (PIB). The evolution over the year 2004 of the factors that contribute to the level of the energy bill is: - the import-export energy quantity differential: +7.5%, - the import-export energy cost differential (in Usa dollar): +27.1%, and - the fall of the dollar: -9.1%. (A.C.)

Canonical and Non-Canonical Aspects of JAK–STAT Signaling: Lessons from Interferons for Cytokine Responses

Science.gov (United States)

Majoros, Andrea; Platanitis, Ekaterini; Kernbauer-Hölzl, Elisabeth; Rosebrock, Felix; Müller, Mathias; Decker, Thomas

2017-01-01

Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. In recent years, several deviations from this paradigm were reported. These include kinase-independent JAK functions as well as extra- and intranuclear activities of U-STATs without phosphotyrosines. Additionally, transcriptional control by STAT complexes resembling neither GAF nor ISGF3 contributes to transcriptome changes in IFN-treated cells. Our review summarizes the contribution of non-canonical JAK–STAT signaling to the innate antimicrobial immunity imparted by IFN. Moreover, we touch upon functions of IFN pathway proteins beyond the IFN response. These include metabolic functions of IRF9 as well as the regulation of natural killer cell activity by kinase-dead TYK2 and different phosphorylation isoforms of STAT1. PMID:28184222

Electronic work sheets for nuclear equipment dimensioning according to AD-Merkblaetter

International Nuclear Information System (INIS)

Rodrigues, P.R.B.

1994-01-01

The purpose of this paper is to show the capability of Work sheet applications in solving engineering problems in a much easier way than by using languages such as Fortran, BASIC etc., once many routines that would have to be developed in these languages for printing and display on screen, just to give a few instances, are already included in the Work sheet application. It is also worth mentioning the fact the never version of the Excel, version 5,0, includes the Object-oriented language Visual Basic, thus making it possible to develop routines for customization as well as compiling interactive routines speeding up the program. (author). 2 refs, 8 figs, 2 tabs

Essential role of Stat6 in IL-4 signalling.

Science.gov (United States)

Takeda, K; Tanaka, T; Shi, W; Matsumoto, M; Minami, M; Kashiwamura, S; Nakanishi, K; Yoshida, N; Kishimoto, T; Akira, S

1996-04-18

Interleukin-4 (IL-4) is a pleiotropic lymphokine which plays an important role in the immune system. IL-4 activates two distinct signalling pathways through tyrosine phosphorylation of Stat6, a signal transducer and activator of transcription, and of a 170K protein called 4PS. To investigate the functional role of Stat6 in IL-4 signalling, we generated mice deficient in Stat6 by gene targeting. We report here that in the mutant mice, expression of CD23 and major histocompatibility complex (MHC) class II in resting B cells was not enhanced in response to IL-4. IL-4 induced B-cell proliferation costimulated by anti-IgM antibody was abolished. The T-cell proliferative response was also notably reduced. Furthermore, production of Th2 cytokines from T cells as well as IgE and IgG1 responses after nematode infection were profoundly reduced. These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses.

Rupture of nanoscaled water sheets in the presence of an applied electric field

Energy Technology Data Exchange (ETDEWEB)

Gopan, Nandu, E-mail: nandug@jncasr.ac.in [Engineering Mechanics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore-560 064 (India)

2016-12-15

Understanding the behaviour of water sheets is relevant in numerous areas, such as thin film coating and atomisation. The rupture of planar liquid sheets are interesting due to the fact that they are objects of co-dimension 1. Previous work seems to suggest that a generic route to liquid structure fragmentation is via liquid sheets. The interplay between inertia, surface tension and viscosity is crucial in determining the dynamics of liquid sheets at a macro scale. At the nanoscale, where thermal fluctuations are expected to play a dominant role, the dynamics become more interesting. The stability and rupture dynamics of nanoscaled water sheets, at constant temperature, are studied using constrained molecular dynamics (MD) simulations. The SPC/E potential with long range electrostatics is used to simulate water molecules. The effect of an applied electric field on the stability of the nanoscaled water sheet forms the focus of this study. The effect of the initial configuration is studied by changing the random seed values used for velocity initialisation. The effect of sheet thickness on the rupture dynamics is also explored. It is seen that when large electric fields (5 V/nm) act across very thin sheets (1 layer), then breakup into multiple ellipsoidal structures is a possibility, and the response of the fluid structure to the applied electric field is non-linear. Furthermore, it is seen that Taylor's predictions for the critical electric field intensity, based on classical electro-hydrodynamics for the onset of instability in macroscopic drops, scales surprisingly well for the case of nanoscaled sheets. (paper)

Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth

Directory of Open Access Journals (Sweden)

Florian M. Corvinus

2005-06-01

Full Text Available Colorectal carcinoma (CRC is a major cause of morbidity and mortality in Western countries. It has so far been molecularly defined mainly by alterations of the Wnt pathway. We show here for the first time that aberrant activities of the signal transducer and activator of transcription STAT3 actively contribute to this malignancy and, thus, are a potential therapeutic target for CRC. Constitutive STAT3 activity was found to be abundant in dedifferentiated cancer cells and infiltrating lymphocytes of CRC samples, but not in non-neoplastic colon epithelium. Cell lines derived from malignant colorectal tumors lost persistent STAT3 activity in culture. However, implantation of colon carcinoma cells into nude mice resulted in restoration of STAT3 activity, suggesting a role of an extracellular stimulus within the tumor microenvironment as a trigger for STAT activation. STAT3 activity in CRC cells triggered through interleukin-6 or through a constitutively active STAT3 mutant promoted cancer cell multiplication, whereas STAT3 inhibition through a dominant-negative variant impaired IL-6-driven proliferation. Blockade of STAT3 activation in CRCderived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.

Leptin Suppresses the Rewarding Effects of Running via STAT3 Signaling in Dopamine Neurons.

Science.gov (United States)

Fernandes, Maria Fernanda A; Matthys, Dominique; Hryhorczuk, Cécile; Sharma, Sandeep; Mogra, Shabana; Alquier, Thierry; Fulton, Stephanie

2015-10-06

The adipose hormone leptin potently influences physical activity. Leptin can decrease locomotion and running, yet the mechanisms involved and the influence of leptin on the rewarding effects of running ("runner's high") are unknown. Leptin receptor (LepR) signaling involves activation of signal transducer and activator of transcription-3 (STAT3), including in dopamine neurons of the ventral tegmental area (VTA) that are essential for reward-relevant behavior. We found that mice lacking STAT3 in dopamine neurons exhibit greater voluntary running, an effect reversed by viral-mediated STAT3 restoration. STAT3 deletion increased the rewarding effects of running whereas intra-VTA leptin blocked it in a STAT3-dependent manner. Finally, STAT3 loss-of-function reduced mesolimbic dopamine overflow and function. Findings suggest that leptin influences the motivational effects of running via LepR-STAT3 modulation of dopamine tone. Falling leptin is hypothesized to increase stamina and the rewarding effects of running as an adaptive means to enhance the pursuit and procurement of food. Copyright © 2015 Elsevier Inc. All rights reserved.

JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana.

Science.gov (United States)

Geng, Tao; Lv, Ding-Ding; Huang, Yu-Xia; Hou, Cheng-Xiang; Qin, Guang-Xing; Guo, Xi-Jie

2016-12-20

Innate immunity was critical in insects defensive system and able to be induced by Janus kinase/signal transducer and activator of transcription cascade transduction (JAK/STAT) signaling pathway. Currently, it had been identified many JAK/STAT signaling pathway-related genes in silkworm, but little function was known on insect innate immunity. To explore the roles of JAK/STAT pathway in antifungal immune response in silkworm (Bombyx mori) against Beauveria bassiana infection, the expression patterns of B. mori C-type lectin 5 (BmCTL5) and genes encoding 6 components of JAK/STAT signaling pathway in silkworm challenged by B. bassiana were analyzed using quantitative real time PCR. Meanwhile the activation of JAK/STAT signaling pathway by various pathogenic micro-organisms and the affect of JAK/STAT signaling pathway inhibitors on antifungal activity in silkworm hemolymph was also detected. Moreover, RNAi assay of BmCTL5 and the affect on expression levels of signaling factors were also analyzed. We found that JAK/STAT pathway could be obviously activated in silkworm challenged with B. bassiana and had no response to bacteria and B. mori cytoplasmic polyhedrosis virus (BmCPV). However, the temporal expression patterns of JAK/STAT signaling pathway related genes were significantly different. B. mori downstream receptor kinase (BmDRK) might be a positive regulator of JAK/STAT signaling pathway in silkworm against B. bassiana infection. Moreover, antifungal activity assay showed that the suppression of JAK/STAT signaling pathway by inhibitors could significantly inhibit the antifungal activity in hemolymph and resulted in increased sensitivity of silkworm to B. bassiana infection, indicating that JAK/STAT signaling pathway might be involved in the synthesis and secretion of antifungal substances. The results of RNAi assays suggested that BmCTL5 might be one pattern recognition receptors for JAK/STAT signaling pathway in silkworm. These findings yield insights for better

Variants within STAT genes reveal association with anticitrullinated protein antibody-negative rheumatoid arthritis in 2 European populations.

Science.gov (United States)

Seddighzadeh, Maria; Gonzalez, Antonio; Ding, Bo; Ferreiro-Iglesias, Aida; Gomez-Reino, Juan J; Klareskog, Lars; Alfredsson, Lars; Dunussi-Joannopoulos, Kyri; Clark, James D; Padyukov, Leonid

2012-08-01

STAT3 and 4 are, among other factors, critical for the interleukin 12 (IL-12)-mediated Th1 response, for transfer of IL-23 signals, and for survival and expansion of Th17 cells. We investigated the association of STAT3 and STAT4 polymorphisms with serologically distinct subgroups of rheumatoid arthritis (RA). A total of 41 single-nucleotide polymorphisms (SNP) within STAT3 and STAT1-STAT4 loci were investigated in a Swedish cohort of 2043 RA cases and 1115 controls. Nine of the associated SNP were tested in a Spanish cohort of 1223 RA cases and 1090 controls. Fourteen SNP in the STAT3 and STAT1-STAT4 loci were associated with anticitrullinated protein antibody (ACPA)-negative RA in the Swedish cohort. Three of the SNP in STAT4 and 2 SNP in STAT3 remained associated with ACPA-negative RA after considering the Spanish results. In addition, rs7574865 and rs10181656, in STAT4, were associated with ACPA-positive RA in the Swedish study. One of these SNP, rs7574865, showed a similar pattern of the association in serologically distinct subgroups of RA in a metaanalysis of all 7 published studies. Our findings suggest that variants in STAT genes may contribute differentially to susceptibility to RA in seropositive and in seronegative patients.

Stat5 signaling specifies basal versus stress erythropoietic responses through distinct binary and graded dynamic modalities.

Directory of Open Access Journals (Sweden)

Ermelinda Porpiglia

2012-08-01

Full Text Available Erythropoietin (Epo-induced Stat5 phosphorylation (p-Stat5 is essential for both basal erythropoiesis and for its acceleration during hypoxic stress. A key challenge lies in understanding how Stat5 signaling elicits distinct functions during basal and stress erythropoiesis. Here we asked whether these distinct functions might be specified by the dynamic behavior of the Stat5 signal. We used flow cytometry to analyze Stat5 phosphorylation dynamics in primary erythropoietic tissue in vivo and in vitro, identifying two signaling modalities. In later (basophilic erythroblasts, Epo stimulation triggers a low intensity but decisive, binary (digital p-Stat5 signal. In early erythroblasts the binary signal is superseded by a high-intensity graded (analog p-Stat5 response. We elucidated the biological functions of binary and graded Stat5 signaling using the EpoR-HM mice, which express a "knocked-in" EpoR mutant lacking cytoplasmic phosphotyrosines. Strikingly, EpoR-HM mice are restricted to the binary signaling mode, which rescues these mice from fatal perinatal anemia by promoting binary survival decisions in erythroblasts. However, the absence of the graded p-Stat5 response in the EpoR-HM mice prevents them from accelerating red cell production in response to stress, including a failure to upregulate the transferrin receptor, which we show is a novel stress target. We found that Stat5 protein levels decline with erythroblast differentiation, governing the transition from high-intensity graded signaling in early erythroblasts to low-intensity binary signaling in later erythroblasts. Thus, using exogenous Stat5, we converted later erythroblasts into high-intensity graded signal transducers capable of eliciting a downstream stress response. Unlike the Stat5 protein, EpoR expression in erythroblasts does not limit the Stat5 signaling response, a non-Michaelian paradigm with therapeutic implications in myeloproliferative disease. Our findings show how the

Lactococcus lactis KR-050L inhibit IL-6/STAT3 activation.

Science.gov (United States)

Hwang, J T; Jang, H-J; Kim, J H; Park, C S; Kim, Y; Lim, C-H; Lee, S W; Rho, M-C

2017-05-01

The purpose of this study was to investigate IL-6/STAT3 inhibitory activity using lactic acid bacteria (LABs) isolated from Gajuknamu kimchi. Six LABs were isolated from Gajuknamu kimchi and identified through 16S rRNA sequencing. Among them, the culture broth of Lactococcus lactis KR-050L inhibited IL-6-induced STAT3 luciferase activity. Fifteen compounds were isolated from the EtOAc extract of culture broth though column chromatography and preparative high-performance liquid chromatography, and they were identified as 2,5-diketopipperazine structures by spectroscopic analyses (MS, 1 H- and 13 C-NMR). They also showed inhibitory activities on IL-6-induced STAT3 activation, and showed the different in activity according to the presence of a phenylalanine residue, hydroxyl groups and isometric structure. The six new LABs isolated from Gajuknamu kimchi, and Lc. lactis KR-050L was selected as candidate IL-6/STAT3 inhibitors. The activity levels of 15 2,5-DKPs isolated from Lc. lactis KR-050L were verified. This study constitutes the first attempt to isolate various LABs from Gajuknamu kimchi and to discover IL-6/STAT3 inhibitors in the EtOAc extract of Lc. lactis KR-050L culture broth. Moreover, our data provide useful biochemical information regarding the commercialization of Lc. lactis isolated from Gajuknamu kimchi as an approach to use functional foods for the treatment of various diseases via IL-6/STAT3 activation. © 2017 The Society for Applied Microbiology.

Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma

DEFF Research Database (Denmark)

Sibbesen, Nina A; Kopp, Katharina L; Litvinov, Ivan V

2015-01-01

the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection...

Decontamination sheet

International Nuclear Information System (INIS)

Hirose, Emiko; Kanesaki, Ken.

1995-01-01

The decontamination sheet of the present invention is formed by applying an adhesive on one surface of a polymer sheet and releasably appending a plurality of curing sheets. In addition, perforated lines are formed on the sheet, and a decontaminating agent is incorporated in the adhesive. This can reduce the number of curing operation steps when a plurality steps of operations for radiation decontamination equipments are performed, and further, the amount of wastes of the cured sheets, and operator's exposure are reduced, as well as an efficiency of the curing operation can be improved, and propagation of contamination can be prevented. (T.M.)

Mutually exclusive STAT1 modifications identified by Ubc9/substrate dimerization-dependent SUMOylation.

Science.gov (United States)

Zimnik, Susan; Gaestel, Matthias; Niedenthal, Rainer

2009-03-01

Post-translational modifications control the physiological activity of the signal transducer and activator of transcription STAT1. While phosphorylation at tyrosine Y701 is a prerequisite for STAT1 dimerization, its SUMOylation represses the transcriptional activity. Recently, we have demonstrated that SUMOylation at lysine K703 inhibits the phosphorylation of nearby localized Y701 of STAT1. Here, we analysed the influence of phosphorylation of Y701 on SUMOylation of K703 in vivo. For that reason, an Ubc9/substrate dimerization-dependent SUMOylation (USDDS) system was developed, which consists of fusions of the SUMOylation substrate and of the SUMO-conjugating enzyme Ubc9 to the chemically activatable heterodimerization domains FKBP and FRB, respectively. When FKBP fusion proteins of STAT1, p53, CRSP9, FOS, CSNK2B, HES1, TCF21 and MYF6 are coexpressed with Ubc9-FRB, treatment of HEK293 cells with the rapamycin-related dimerizer compound AP21967 induces SUMOylation of these proteins in vivo. For STAT1-FKBP and p53-FKBP we show that this SUMOylation takes place at their specific SUMOylation sites in vivo. Using USDDS, we then demonstrate that STAT1 phosphorylation at Y701 induced by interferon-beta treatment inhibits SUMOylation of K703 in vivo. Thus, pY701 and SUMO-K703 of STAT1 represent mutually exclusive modifications, which prevent signal integration at this molecule and probably ensure the existence of differentially modified subpopulations of STAT1 necessary for its regulated nuclear cytoplasmic activation/inactivation cycle.

Unphosphorylated STAT3 modulates alpha7 nicotinic receptor signaling and cytokine production in sepsis

NARCIS (Netherlands)

Peña, Geber; Cai, Bolin; Liu, Jun; van der Zanden, Esmerij P.; Deitch, Edwin A.; de Jonge, Wouter J.; Ulloa, Luis

2010-01-01

The role of STAT3 in infectious diseases remains undetermined, in part because unphosphorylated STAT3 has been considered an inactive protein. Here, we report that unphosphorylated STAT3 contributes to cholinergic anti-inflammation, prevents systemic inflammation, and improves survival in sepsis.

Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and migration

International Nuclear Information System (INIS)

Arulanandam, Rozanne; Geletu, Mulu; Feracci, Helene; Raptis, Leda

2010-01-01

Rac1 (Rac) is a member of the Rho family of small GTPases which controls cell migration by regulating the organization of actin filaments. Previous results suggested that mutationally activated forms of the Rho GTPases can activate the Signal Transducer and Activator of Transcription-3 (Stat3), but the exact mechanism is a matter of controversy. We recently demonstrated that Stat3 activity of cultured cells increases dramatically following E-cadherin engagement. To better understand this pathway, we now compared Stat3 activity levels in mouse HC11 cells before and after expression of the mutationally activated Rac1 (Rac V12 ), at different cell densities. The results revealed for the first time a dramatic increase in protein levels and activity of both the endogenous Rac and Rac V12 with cell density, which was due to inhibition of proteasomal degradation. In addition, Rac V12 -expressing cells had higher Stat3, tyrosine-705 phosphorylation and activity levels at all densities, indicating that Rac V12 is able to activate Stat3. Further examination of the mechanism of Stat3 activation showed that Rac V12 expression caused a surge in mRNA of Interleukin-6 (IL6) family cytokines, known potent Stat3 activators. Knockdown of gp130, the common subunit of this family reduced Stat3 activity, indicating that these cytokines may be responsible for the Stat3 activation by Rac V12 . The upregulation of IL6 family cytokines was required for cell migration and proliferation induced by Rac V12 , as shown by gp130 knockdown experiments, thus demonstrating that the gp130/Stat3 axis represents an essential effector of activated Rac for the regulation of key cellular functions.

Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and migration

Energy Technology Data Exchange (ETDEWEB)

Arulanandam, Rozanne; Geletu, Mulu [Departments of Microbiology and Immunology and Pathology and Molecular Medicine, and Queen' s University Cancer Institute, Queen' s University, Botterell Hall, Rm. 713, Kingston, Ontario, Canada K7L 3N6 (Canada); Feracci, Helene [Universite Bordeaux 1, Centre de Recherche Paul Pascal, CNRS UPR 8641, 33600 Pessac (France); Raptis, Leda, E-mail: raptisl@queensu.ca [Departments of Microbiology and Immunology and Pathology and Molecular Medicine, and Queen' s University Cancer Institute, Queen' s University, Botterell Hall, Rm. 713, Kingston, Ontario, Canada K7L 3N6 (Canada)

2010-03-10

Rac1 (Rac) is a member of the Rho family of small GTPases which controls cell migration by regulating the organization of actin filaments. Previous results suggested that mutationally activated forms of the Rho GTPases can activate the Signal Transducer and Activator of Transcription-3 (Stat3), but the exact mechanism is a matter of controversy. We recently demonstrated that Stat3 activity of cultured cells increases dramatically following E-cadherin engagement. To better understand this pathway, we now compared Stat3 activity levels in mouse HC11 cells before and after expression of the mutationally activated Rac1 (Rac{sup V12}), at different cell densities. The results revealed for the first time a dramatic increase in protein levels and activity of both the endogenous Rac and Rac{sup V12} with cell density, which was due to inhibition of proteasomal degradation. In addition, Rac{sup V12}-expressing cells had higher Stat3, tyrosine-705 phosphorylation and activity levels at all densities, indicating that Rac{sup V12} is able to activate Stat3. Further examination of the mechanism of Stat3 activation showed that Rac{sup V12} expression caused a surge in mRNA of Interleukin-6 (IL6) family cytokines, known potent Stat3 activators. Knockdown of gp130, the common subunit of this family reduced Stat3 activity, indicating that these cytokines may be responsible for the Stat3 activation by Rac{sup V12}. The upregulation of IL6 family cytokines was required for cell migration and proliferation induced by Rac{sup V12}, as shown by gp130 knockdown experiments, thus demonstrating that the gp130/Stat3 axis represents an essential effector of activated Rac for the regulation of key cellular functions.

Functions of the Drosophila JAK-STAT pathway

Science.gov (United States)

Amoyel, Marc; Bach, Erika A.

2012-01-01

JAK-STAT signaling has been proposed to act in numerous stem cells in a variety of organisms. Here we provide an overview of its roles in three well characterized stem cell populations in Drosophila, in the intestine, lymph gland and testis. In flies, there is a single JAK and a single STAT, which has made the genetic dissection of pathway function considerably easier and facilitated the analysis of communication between stem cells, their niches and offspring. Studies in flies have revealed roles for this pathway as diverse as regulating bona fide intrinsic self-renewal, integrating response to environmental cues that control quiescence and promoting mitogenic responses to stress. PMID:24058767

[Study on the correlation between EGFR-STAT3 signal pathway and laryngeal papilloma].

Science.gov (United States)

Wang, Xinhua; Sun, Jingwu

2009-09-01

To explore the relationship between the expression of EGFR and STAT3 in human laryngeal papilloma and its biological behavior. Reverse transcription polymerase chain reaction(RT-PCR), immunohistochemical staining and Western blot were used to evaluate the mRNA and protein expression of EGFR and STAT3 (p-STAT3) in 42 laryngeal papilloma tissues and 15 samples of normal laryngeal tissue, and the relationship between the protein expression of them and clinic pathological parameters was also analyzed. The mRNA expression levels of EGFR and STAT3 in laryngeal papilloma tissue were significantly higher than that in normal laryngeal tissue (P papilloma than normal laryngeal tissue by immunohistochemistry and western blot (P papilloma (P papilloma (P papilloma,, and the persistent activation of STAT3 gene plays an important role in the recurrence and canceration of laryngeal papilloma.

Signal Transducer and Activator of Transcription 1 (STAT1) Knock-down Induces Apoptosis in Malignant Pleural Mesothelioma.

Science.gov (United States)

Arzt, Lisa; Halbwedl, Iris; Gogg-Kamerer, Margit; Popper, Helmut H

2017-07-01

Malignant pleural mesothelioma (MPM) is the most common primary tumor of the pleura. Its incidence is still increasing in Europe and the prognosis remains poor. We investigated the oncogenic function of signal transducer and activator of transcription 1 (STAT1) in MPM in more detail. A miRNA profiling was performed on 52 MPM tissue samples. Upregulated miRNAs (targeting SOCS1/3) were knocked-down using miRNA inhibitors. mRNA expression levels of STAT1/3, SOCS1/3 were detected in MPM cell lines. STAT1 has been knocked-down using siRNA and qPCR was used to detect mRNA expression levels of all JAK/STAT family members and genes that regulate them. An immunohistochemical staining was performed to detect the expression of caspases. STAT1 was upregulated and STAT3 was downregulated, SOCS1/3 protein was not detected but it was possible to detect SOCS1/3 mRNA in MPM cell lines. The upregulated miRNAs were successfully knocked-down, however the expected effect on SOCS1 expression was not detected. STAT1 knock-down had different effects on STAT3/5 expression. Caspase 3a and 8 expression was found to be increased after STAT1 knock-down. The physiologic regulation of STAT1 via SOCS1 is completely lost in MPM and it does not seem that the miRNAs identified by now, do inhibit the expression of SOCS1. MPM cell lines compensate STAT1 knock-down by increasing the expression of STAT3 or STAT5a, two genes which are generally considered to be oncogenes. And much more important, STAT1 knock-down induces apoptosis in MPM cell lines and STAT1 might therefore be a target for therapeutic intervention.

Inborn errors of human STAT1: allelic heterogeneity governs the diversity of immunological and infectious phenotypes

Science.gov (United States)

Boisson-Dupuis, Stephanie; Kong, Xiao-Fei; Okada, Satoshi; Cypowyj, Sophie; Puel, Anne; Abel, Laurent; Casanova, Jean-Laurent

2012-01-01

The genetic dissection of various human infectious diseases has led to the definition of inborn errors of human STAT1 immunity of four types, including (i) autosomal recessive (AR) complete STAT1 deficiency, (ii) AR partial STAT1 deficiency, (iii) autosomal dominant (AD) STAT1 deficiency, and (iv) AD gain of STAT1 activity. The two types of AR STAT1 defect give rise to a broad infectious phenotype with susceptibility to intramacrophagic bacteria (mostly mycobacteria) and viruses (herpes viruses at least), due principally to the impairment of IFN-γ-mediated and IFN-α/β-mediated immunity, respectively. Clinical outcome depends on the extent to which the STAT1 defect decreases responsiveness to these cytokines. AD STAT1 deficiency selectively predisposes individuals to mycobacterial disease, owing to the impairment of IFN-γ-mediated immunity, as IFN-α/β-mediated immunity is maintained. Finally, AD gain of STAT1 activity is associated with autoimmunity, probably owing to an enhancement of IFN-α/β-mediated immunity. More surprisingly, it is also associated with chronic mucocutaneous candidiasis, through as yet undetermined mechanisms involving an inhibition of the development of IL-17-producing T cells. Thus, germline mutations in human STAT1 define four distinct clinical disorders. Various combinations of viral, mycobacterial and fungal infections are therefore allelic at the human STAT1 locus. These experiments of Nature neatly highlight the clinical and immunological impact of the human genetic dissection of infectious phenotypes. PMID:22651901

Three STATs are involved in the regulation of the expression of antimicrobial peptides in the triangle sail mussel, Hyriopsis cumingii.

Science.gov (United States)

Dai, Yun-Jia; Hui, Kai-Min; Zhang, Ying-Hao; Liu, Yan; Wang, Yu-Qing; Zhao, Li-Juan; Lin, Li; Chai, Lian-Qin; Wei, Shun; Lan, Jiang-Feng

2017-04-01

Janus kinase (Jak) and signal transducers and activators of transcription (STAT) signaling pathway is associated in antiviral and antibacterial immune response. Previous studies primarily investigated the function of STATs in mammals. For most invertebrates, only one STAT was found in each species, such as STAT92E was found in Drosophila melanogaster. The studies, which focus on the functional difference between various STATs in the same species of invertebrate, are limited. In the present study, three STATs (HcSTAT1, HcSTAT2 and HcSTAT3) were identified in triangle shell pearl mussel, Hyriopsis cumingii. Phylogenetic analysis showed that HcSTAT1 and HcSTAT3 were clustered with Homo sapiens STAT5, and HcSTAT2 was clustered with Pinctada fucata STAT and Crassostea gigas STAT6. All three STATs could be detected in all tested tissues (hemocytes, hepatopancreas, gill, mantle and foot), and were induced expression when challenged with Staphylococcus aureus or Aeromonas hydrophilia in hemocytes and hepatopancreas. HcSTAT1 regulated the expression of HcDef, HcWAP, HcThe and HcTNF. The expression of HcWAP and HcTNF was down-regulated in HcSTAT2-RNAi mussel. And HcSTAT3 affected the expression of HcTNF. The study is the first report of different functions in antibacterial immune responses between STATs in mollusks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lung Adenocarcinomas and Lung Cancer Cell Lines Show Association of MMP-1 Expression With STAT3 Activation

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Alexander Schütz

2015-04-01

Full Text Available Signal transducer and activator of transcription 3 (STAT3 is constitutively activated in the majority of lung cancer. This study aims at defining connections between STAT3 function and the malignant properties of non–small cell lung carcinoma (NSCLC cells. To address possible mechanisms by which STAT3 influences invasiveness, the expression of matrix metalloproteinase-1 (MMP-1 was analyzed and correlated with the STAT3 activity status. Studies on both surgical biopsies and on lung cancer cell lines revealed a coincidence of STAT3 activation and strong expression of MMP-1. MMP-1 and tyrosine-phosphorylated activated STAT3 were found co-localized in cancer tissues, most pronounced in tumor fronts, and in particular in adenocarcinomas. STAT3 activity was constitutive, although to different degrees, in the lung cancer cell lines investigated. Three cell lines (BEN, KNS62, and A549 were identified in which STAT3 activitation was inducible by Interleukin-6 (IL-6. In A549 cells, STAT3 activity enhanced the level of MMP-1 mRNA and stimulated transcription from the MMP-1 promoter in IL-6–stimulated A549 cells. STAT3 specificity of this effect was confirmed by STAT3 knockdown through RNA interference. Our results link aberrant activity of STAT3 in lung cancer cells to malignant tumor progression through up-regulation of expression of invasiveness-associated MMPs.

Bayesian Inversion for Large Scale Antarctic Ice Sheet Flow

KAUST Repository

Ghattas, Omar

2015-01-07

The flow of ice from the interior of polar ice sheets is the primary contributor to projected sea level rise. One of the main difficulties faced in modeling ice sheet flow is the uncertain spatially-varying Robin boundary condition that describes the resistance to sliding at the base of the ice. Satellite observations of the surface ice flow velocity, along with a model of ice as a creeping incompressible shear-thinning fluid, can be used to infer this uncertain basal boundary condition. We cast this ill-posed inverse problem in the framework of Bayesian inference, which allows us to infer not only the basal sliding parameters, but also the associated uncertainty. To overcome the prohibitive nature of Bayesian methods for large-scale inverse problems, we exploit the fact that, despite the large size of observational data, they typically provide only sparse information on model parameters. We show results for Bayesian inversion of the basal sliding parameter field for the full Antarctic continent, and demonstrate that the work required to solve the inverse problem, measured in number of forward (and adjoint) ice sheet model solves, is independent of the parameter and data dimensions

Bayesian Inversion for Large Scale Antarctic Ice Sheet Flow

KAUST Repository

Ghattas, Omar

2015-01-01

The flow of ice from the interior of polar ice sheets is the primary contributor to projected sea level rise. One of the main difficulties faced in modeling ice sheet flow is the uncertain spatially-varying Robin boundary condition that describes the resistance to sliding at the base of the ice. Satellite observations of the surface ice flow velocity, along with a model of ice as a creeping incompressible shear-thinning fluid, can be used to infer this uncertain basal boundary condition. We cast this ill-posed inverse problem in the framework of Bayesian inference, which allows us to infer not only the basal sliding parameters, but also the associated uncertainty. To overcome the prohibitive nature of Bayesian methods for large-scale inverse problems, we exploit the fact that, despite the large size of observational data, they typically provide only sparse information on model parameters. We show results for Bayesian inversion of the basal sliding parameter field for the full Antarctic continent, and demonstrate that the work required to solve the inverse problem, measured in number of forward (and adjoint) ice sheet model solves, is independent of the parameter and data dimensions

Inhibition of STAT-3 results in greater cetuximab sensitivity in head and neck squamous cell carcinoma

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Bonner, James A.; Yang, Eddy S.; Trummell, Hoa Q.; Nowsheen, Somaira; Willey, Christopher D.; Raisch, Kevin P.

2011-01-01

Objective: The inhibition of epidermal growth factor receptor (EGFr) with the monoclonal antibody cetuximab reduces cell proliferation and survival which correlates with increased DNA damage. Since the signal transducer and activator of transcription-3 (STAT-3) is involved in the EGFr-induced signaling pathway, we hypothesized that depletion of STAT-3 may augment cetuximab-induced processes in human head and neck cancer cells. Materials and methods: Human head and neck squamous carcinoma cells (UM-SCC-5) were transfected with short hairpin RNA (shRNA) against STAT-3 (STAT3-2.4 and 2.9 cells). A mutated form of this shRNA was transfected for a control (NEG4.17 cells). Radiosensitivity was assessed by a standard colony formation assay. Proliferation was assessed by daily cell counts following treatment and apoptosis was assessed by an annexin V-FITC assay. The alkaline comet assay was used to assess DNA damage. Results: The STAT-3 knockdown cells (STAT3-2.4 and STAT3-2.9 cells) demonstrated enhanced radiosensitivity compared to control NEG4.17 cells, which correlated with increased apoptosis. Also, the STAT-3 knockdown cells demonstrated decreased proliferation with cetuximab treatments compared to control cells (NEG4.17). The increased cetuximab sensitivity of the STAT-3 knockdown cells correlated with increased apoptosis and DNA damage compared to control cells (NEG4.17). Conclusion: These studies revealed that the greater anti-proliferative effects and increased cytotoxicity of cetuximab in the STAT3-2.4 and STAT3-2.9 cells compared to control NEG4.17 cells, may be a result of STAT3-mediated effects on cellular apoptosis and DNA damage.

STAT3 Regulates Proliferation and Immunogenicity of the Ewing Family of Tumors In Vitro

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Sam Behjati

2012-01-01

Full Text Available The Ewing sarcoma family of tumors (ESFT represents an aggressive spectrum of malignant tumour types with common defining histological and cytogenetic features. To evaluate the functional activation of signal transducer and activator of transcription 3 (STAT3 in ESFT, we evaluated its activation in primary tissue sections and observed the functional consequences of its inhibition in ESFT cell lines. STAT3 was activated (tyrosine 705-phosphorylated in 18 out of 31 primary tumours (58%, either diffusely (35% or focally (23%. STAT3 was constitutively activated in 3 out of 3 ESFT cell lines tested, and its specific chemical inhibition resulted in complete loss of cell viability. STAT3 inhibition in ESFT cell lines was associated with several consistent changes in chemokine profile suggesting a role of STAT3 in ESFT in both cell survival and modification of the cellular immune environment. Together these data support the investigation of STAT3 inhibitors for the Ewing family of tumors.

Activation of intestinal epithelial Stat3 orchestrates tissue defense during gastrointestinal infection.

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Nadine Wittkopf

Full Text Available Gastrointestinal infections with EHEC and EPEC are responsible for outbreaks of diarrheal diseases and represent a global health problem. Innate first-line-defense mechanisms such as production of mucus and antimicrobial peptides by intestinal epithelial cells are of utmost importance for host control of gastrointestinal infections. For the first time, we directly demonstrate a critical role for Stat3 activation in intestinal epithelial cells upon infection of mice with Citrobacter rodentium - a murine pathogen that mimics human infections with attaching and effacing Escherichia coli. C. rodentium induced transcription of IL-6 and IL-22 in gut samples of mice and was associated with activation of the transcription factor Stat3 in intestinal epithelial cells. C. rodentium infection induced expression of several antimicrobial peptides such as RegIIIγ and Pla2g2a in the intestine which was critically dependent on Stat3 activation. Consequently, mice with specific deletion of Stat3 in intestinal epithelial cells showed increased susceptibility to C. rodentium infection as indicated by high bacterial load, severe gut inflammation, pronounced intestinal epithelial cell death and dissemination of bacteria to distant organs. Together, our data implicate an essential role for Stat3 activation in intestinal epithelial cells during C. rodentium infection. Stat3 concerts the host response to bacterial infection by controlling bacterial growth and suppression of apoptosis to maintain intestinal epithelial barrier function.

FastStats: Accidents or Unintentional Injuries

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... Women’s Health State and Territorial Data Reproductive Health Contraceptive Use Infertility Reproductive Health Notice Regarding FastStats Mobile ... PDF – 2.3 MB] Drug Overdose Deaths Among Adolescents Aged 15-19 in the United States: 1999- ...

FastStats: Whooping Cough or Pertussis

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... Women’s Health State and Territorial Data Reproductive Health Contraceptive Use Infertility Reproductive Health Notice Regarding FastStats Mobile ... DT/DTaP vaccination: 84.6% (2015) Percent of adolescents aged 13-17 years with 1 dose or ...

Analysis of STAT1 activation by six FGFR3 mutants associated with skeletal dysplasia undermines dominant role of STAT1 in FGFR3 signaling in cartilage.

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Pavel Krejci

Full Text Available Activating mutations in FGFR3 tyrosine kinase cause several forms of human skeletal dysplasia. Although the mechanisms of FGFR3 action in cartilage are not completely understood, it is believed that the STAT1 transcription factor plays a central role in pathogenic FGFR3 signaling. Here, we analyzed STAT1 activation by the N540K, G380R, R248C, Y373C, K650M and K650E-FGFR3 mutants associated with skeletal dysplasias. In a cell-free kinase assay, only K650M and K650E-FGFR3 caused activatory STAT1(Y701 phosphorylation. Similarly, in RCS chondrocytes, HeLa, and 293T cellular environments, only K650M and K650E-FGFR3 caused strong STAT1 activation. Other FGFR3 mutants caused weak (HeLa or no activation (293T and RCS. This contrasted with ERK MAP kinase activation, which was strongly induced by all six mutants and correlated with the inhibition of proliferation in RCS chondrocytes. Thus the ability to activate STAT1 appears restricted to the K650M and K650E-FGFR3 mutants, which however account for only a small minority of the FGFR3-related skeletal dysplasia cases. Other pathways such as ERK should therefore be considered as central to pathological FGFR3 signaling in cartilage.

Overload-mediated skeletal muscle hypertrophy is not impaired by loss of myofiber STAT3.

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Pérez-Schindler, Joaquín; Esparza, Mary C; McKendry, James; Breen, Leigh; Philp, Andrew; Schenk, Simon

2017-09-01

Although the signal pathways mediating muscle protein synthesis and degradation are well characterized, the transcriptional processes modulating skeletal muscle mass and adaptive growth are poorly understood. Recently, studies in mouse models of muscle wasting or acutely exercised human muscle have suggested a potential role for the transcription factor signal transducer and activator of transcription 3 (STAT3), in adaptive growth. Hence, in the present study we sought to define the contribution of STAT3 to skeletal muscle adaptive growth. In contrast to previous work, two different resistance exercise protocols did not change STAT3 phosphorylation in human skeletal muscle. To directly address the role of STAT3 in load-induced (i.e., adaptive) growth, we studied the anabolic effects of 14 days of synergist ablation (SA) in skeletal muscle-specific STAT3 knockout (mKO) mice and their floxed, wild-type (WT) littermates. Plantaris muscle weight and fiber area in the nonoperated leg (control; CON) was comparable between genotypes. As expected, SA significantly increased plantaris weight, muscle fiber cross-sectional area, and anabolic signaling in WT mice, although interestingly, this induction was not impaired in STAT3 mKO mice. Collectively, these data demonstrate that STAT3 is not required for overload-mediated hypertrophy in mouse skeletal muscle. Copyright © 2017 the American Physiological Society.

Fact Sheet: Trigeminal Neuralgia

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Cerebral Aneurysms Fact Sheet

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Marketing Transformation (Fact Sheet)

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DOE Solar Energy Technologies Program

2011-10-13

Through the SunShot Initiative, the U.S. Department of Energy (DOE) works with manufacturers, communities, states, utilities, and other partners to enable the solar market by reducing non-hardware balance-of-system (BOS) costs, developing a skilled workforce, and eliminating market barriers to widespread adoption of solar technologies.

Adolescent Literacy. Fact Sheet

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2011-01-01

The nation's workforce is demanding ever more literate workers and citizens. As technology advances and the American economy grows increasingly knowledge based, individuals must be able to read, write, and communicate at higher levels in order to remain economic and social contributors. A student's level of literacy is a critical determinant of…

Environmental Management Fact Sheets.

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In recent years, the need for nuclear materials has decreased and the Department of Energy (DOE) has focused greater attention on cleaning up contamination left from past activities. The Office of Environmental Management (EM) within DOE is responsible for managing waste and cleaning up contamination at DOE sites across the nation. This collection…

Children's Toys Fact Sheet

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Bremmer HJ; Veen MP van; LMB

2002-01-01

Mathematical models are available for the exposure assessment of compounds in consumer products. The computer program CONSEXPO is used for the calculations. Since the huge number of consumer products does not allow exposure assessment of every product separately, a limited number of main categories

Myasthenia Gravis Fact Sheet

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... or duplicated without permission of the Office on Women’s Health in the U.S. Department of Health and Human Services. Citation of the source is appreciated. Page last updated: March 14, 2018. About Us Who we are What ...

Zika Virus Fact Sheet

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... is caused by a virus transmitted primarily by Aedes mosquitoes. People with Zika virus disease can have symptoms including mild fever, skin ... framework. Q&A: Zika virus and complication ... mosquito from the Aedes genus, mainly Aedes aegypti in tropical regions. Aedes ...

Dietary Supplement Fact Sheets

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Buffer Zone Fact Sheets

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New requirements for buffer zones and sign posting contribute to soil fumigant mitigation and protection for workers and bystanders. The buffer provides distance between the pesticide application site and bystanders, reducing exposure risk.

Ovarian Cancer Fact Sheet

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Uterine Fibroids Fact Sheet

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HSP90 is essential for Jak-STAT signaling in classical Hodgkin lymphoma cells

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Kube Dieter

2009-07-01

Full Text Available Abstract In classical Hodgkin lymphoma (cHL chemotherapeutic regimens are associated with stagnant rates of secondary malignancies requiring the development of new therapeutic strategies. We and others have shown that permanently activated Signal Transducer and Activator of Transcription (STAT molecules are essential for cHL cells. Recently an overexpression of heat-shock protein 90 (HSP90 in cHL cells has been shown and inhibition of HSP90 seems to affect cHL cell survival. Here we analysed the effects of HSP90 inhibition by geldanamycin derivative 17-AAG or RNA interference (RNAi on aberrant Jak-STAT signaling in cHL cells. Treatment of cHL cell lines with 17-AAG led to reduced cell proliferation and a complete inhibition of STAT1, -3, -5 and -6 tyrosine phosphorylation probably as a result of reduced protein expression of Janus kinases (Jaks. RNAi-mediated inhibition of HSP90 showed similar effects on Jak-STAT signaling in L428 cHL cells. These results suggest a central role of HSP90 in permanently activated Jak-STAT signaling in cHL cells. Therapeutics targeting HSP90 may be a promising strategy in cHL and other cancer entities associated with deregulated Jak-STAT pathway activation.

The Role of Epithelial Stat3 in Amelogenesis during Mouse Incisor Renewal.

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Zhang, Bin; Meng, Bo; Viloria, Edward; Naveau, Adrien; Ganss, Bernhard; Jheon, Andrew H

2018-03-16

The aim of this study was to evaluate the role of epithelial signal transducer and activator of transcription 3 (STAT3) in mouse incisor amelogenesis. Since Stat3 is expressed in the epithelial component of developing and adult mouse teeth, we generated and analyzed Krt14Cre/+;Stat3fl/fl mutant mice in which Stat3 was inactivated in epithelia including ameloblast progenitors and ameloblasts, the cells responsible for enamel formation. Histological analysis showed little enamel matrix in mutant incisors compared to controls. Delayed incisor enamel mineralization was demonstrated using micro-computed X-ray tomography analysis and was supported by an increase in the pre-expression distance of enamel-enriched proteins such as amelogenin, ameloblastin, and kallikrein-4. Lastly, scanning electron microscopy analysis showed little enamel mineralization in mutant incisors underneath the mesial root of the 1st molar; however, the micro-architecture of enamel mineralization was similar in the erupted portion of control and mutant incisors. Taken together, our findings demonstrate for the first time that the absence of epithelial Stat3 in mice leads to delayed incisor amelogenesis. © 2018 S. Karger AG, Basel.

The role of STAT3 in leading the crosstalk between human cancers and the immune system.

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Wang, Yu; Shen, Yicheng; Wang, Sinan; Shen, Qiang; Zhou, Xuan

2018-02-28

The development and progression of human cancers are continuously and dynamically regulated by intrinsic and extrinsic factors. As a converging point of multiple oncogenic pathways, signal transducer and activator of transcription 3 (STAT3) is constitutively activated both in tumor cells and tumor-infiltrated immune cells. Activated STAT3 persistently triggers tumor progression through direct regulation of oncogenic gene expression. Apart from its oncogenic role in regulating gene expression in tumor cells, STAT3 also paves the way for human cancer growth through immunosuppression. Activated STAT3 in immune cells results in inhibition of immune mediators and promotion of immunosuppressive factors. Therefore, STAT3 modulates the interaction between tumor cells and host immunity. Accumulating evidence suggests that targeting STAT3 may enhance anti-cancer immune responses and rescue the suppressed immunologic microenvironment in tumors. Taken together, STAT3 has emerged as a promising target in cancer immunotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Inactivation of STAT3 Signaling Impairs Hair Cell Differentiation in the Developing Mouse Cochlea.

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Chen, Qianqian; Quan, Yizhou; Wang, Naitao; Xie, Chengying; Ji, Zhongzhong; He, Hao; Chai, Renjie; Li, Huawei; Yin, Shankai; Chin, Y Eugene; Wei, Xunbin; Gao, Wei-Qiang

2017-07-11

Although STAT3 signaling is demonstrated to regulate sensory cell differentiation and regeneration in the zebrafish, its exact role is still unclear in mammalian cochleae. Here, we report that STAT3 and its activated form are specifically expressed in hair cells during mouse cochlear development. Importantly, conditional cochlear deletion of Stat3 leads to an inhibition on hair cell differentiation in mice in vivo and in vitro. By cell fate analysis, inactivation of STAT3 signaling shifts the cell division modes from asymmetric to symmetric divisions from supporting cells. Moreover, inhibition of Notch signaling stimulates STAT3 phosphorylation, and inactivation of STAT3 signaling attenuates production of supernumerary hair cells induced by a Notch pathway inhibitor. Our findings highlight an important role of the STAT3 signaling during mouse cochlear hair cell differentiation and may have clinical implications for the recovery of hair cell loss-induced hearing impairment. Copyright © 2017 International Society for Stem Cell Research. Published by Elsevier Inc. All rights reserved.

Inactivation of STAT3 Signaling Impairs Hair Cell Differentiation in the Developing Mouse Cochlea

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Qianqian Chen

2017-07-01

Full Text Available Although STAT3 signaling is demonstrated to regulate sensory cell differentiation and regeneration in the zebrafish, its exact role is still unclear in mammalian cochleae. Here, we report that STAT3 and its activated form are specifically expressed in hair cells during mouse cochlear development. Importantly, conditional cochlear deletion of Stat3 leads to an inhibition on hair cell differentiation in mice in vivo and in vitro. By cell fate analysis, inactivation of STAT3 signaling shifts the cell division modes from asymmetric to symmetric divisions from supporting cells. Moreover, inhibition of Notch signaling stimulates STAT3 phosphorylation, and inactivation of STAT3 signaling attenuates production of supernumerary hair cells induced by a Notch pathway inhibitor. Our findings highlight an important role of the STAT3 signaling during mouse cochlear hair cell differentiation and may have clinical implications for the recovery of hair cell loss-induced hearing impairment.

Influence of genetic polymorphisms of IL23R, STAT3, IL12B, and STAT4 on the risk of aplastic anemia and the effect of immunosuppressive therapy.

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Zhao, Li; Zhu, Huanling; Han, Bing; Wang, Lixin; Sun, Yuming; Lu, Xiaojun; Huang, Chunyan; Tan, Bin; Chen, Chunxia; Qin, Li

2018-04-01

Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related genes may contribute to AA risk. In the current study, we investigated the association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. In the current 164 AA cases and 211 controls study, we found T allele and TT genotype of rs7574865 were more frequent in the cases than that in the controls. In the additive model, individual carrying rs7574865 T allele demonstrated a 37% (OR (95% CI) = 1.37 (1.02-1.85), Pper = 0.036) increased AA risk. In the recessive model, carrier with rs7574865 TT genotype showed a 2.08-fold increased AA risk (OR (95% CI) = 2.08 (1.14-3.70), Pper = 0.017). Additionally, we showed that G allele and GG genotype of rs11209032 were more frequent in the 88 non-severe AA cases than that in the 76 severe AA ones. Our study also found G allele and GG genotype of rs11209032, and GG-genotype of rs744166 associated with the immunosuppressive therapy outcome in AA patients. Current study results support that functional STAT4 (rs7574865), IL23R (rs11209032), and STAT3 (rs744166) variants may associate with occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China.

Regulation of c–myc expression by IFN–γ through Stat1-dependent and -independent pathways

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Ramana, Chilakamarti V.; Grammatikakis, Nicholas; Chernov, Mikhail; Nguyen, Hannah; Goh, Kee Chuan; Williams, Bryan R.G.; Stark, George R.

2000-01-01

Interferons (IFNs) inhibit cell growth in a Stat1-dependent fashion that involves regulation of c–myc expression. IFN–γ suppresses c–myc in wild-type mouse embryo fibroblasts, but not in Stat1-null cells, where IFNs induce c–myc mRNA rapidly and transiently, thus revealing a novel signaling pathway. Both tyrosine and serine phosphorylation of Stat1 are required for suppression. Induced expression of c–myc is likely to contribute to the proliferation of Stat1-null cells in response to IFNs. IFNs also suppress platelet-derived growth factor (PDGF)-induced c–myc expression in wild-type but not in Stat1-null cells. A gamma-activated sequence element in the promoter is necessary but not sufficient to suppress c–myc expression in wild-type cells. In PKR-null cells, the phosphorylation of Stat1 on Ser727 and transactivation are both defective, and c–myc mRNA is induced, not suppressed, in response to IFN–γ. A role for Raf–1 in the Stat1-independent pathway is revealed by studies with geldanamycin, an HSP90-specific inhibitor, and by expression of a mutant of p50cdc37 that is unable to recruit HSP90 to the Raf–1 complex. Both agents abrogated the IFN–γ-dependent induction of c–myc expression in Stat1-null cells. PMID:10637230

A meta-analysis of the association of STAT4 polymorphism with systemic lupus erythematosus.

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Yuan, Hui; Feng, Jin-Bao; Pan, Hai-Feng; Qiu, Li-Xin; Li, Lian-Hong; Zhang, Ning; Ye, Dong-Qing

2010-06-01

STAT4 has been newly identified as a susceptibility gene for systemic lupus erythematosus (SLE) in recent reports. To more precisely estimate the association between STAT4 polymorphism and SLE risk, a meta-analysis was performed. Studies on the association of STAT4 rs7574865 or rs7601754 with SLE were fully considered and carefully selected using three electronic databases (PubMed, Embase, and Web of Science). A total of 17 comparisons from 8 relevant studies involving 7,381 patients and 11,431 controls were included to analyze the association between STAT4 rs7574865 and SLE risk. The pooled OR for the minor T allele of STAT4 rs7574865 was 1.65 (95% CI 1.56-1.75, P rs7574865 with SLE susceptibility was similar in populations of European or Asian origin, although significant differences in the minor T allele frequencies were observed in the two population controls. As for rs7601754, there were five comparisons from four relevant studies involving 2,498 patients and 4,825 controls in this meta-analysis. The pooled OR for the minor C allele of STAT4 rs7601754 was 0.67 (95% CI 0.59-0.75, P rs7574865 polymorphism as a susceptibility factor for SLE in populations of European and Asian origin. Our results also suggest that STAT4 rs7601754 polymorphism might be associated with SLE risk.