AVIATION COMPETITION: Regional Jet Service Yet to Reach Many Small Communities

DTIC Science & Technology

2001-02-01

1997), AA (2000), NW (2000) Colorado Springs CO DL (1997), CO (1999), HP (1999) Columbia SC DL (1997), CO (1998), UA (1999), US (1999) Corpus...DL (1999) Small cities Bangor ME DL (1999) Bozeman MT DL (1997), UA (2000) Butte MT DL (1997) Casper WY DL (1997) Durango CO HP (1999) Grand Forks ND

77 FR 9839 - Amendment of Class D and Class E Airspace, and Establishment of Class E Airspace; Bozeman, MT

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-21

..., to accommodate aircraft using Instrument Landing System (ILS) Localizer (LOC) standard instrument... 6005 Class E airspace areas extending upward from 700 feet or more above the surface of the earth...

A Proven Method for Cooperative Teaching Model between Universities and Public School Partnership Programs.

ERIC Educational Resources Information Center

Herbster, Douglas L.; And Others

A partnership was developed between the Bozeman (Montana) Public School District (BPSD) and the Montana State University (MSU) College of Education, Health, and Human Development. The purpose of the partnership was to foster collaboration between the two groups to improve the quality of K-12 education in the Bozeman District and to improve the…

75 FR 32738 - Gallatin National Forest-Hebgen Lake Ranger District; MT; Lonesome Wood Vegetation Management...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-09

...; Lonesome Wood Vegetation Management Project 2 AGENCY: Forest Service, USDA. ACTION: Notice of Intent to prepare an Environmental Impact Statement. SUMMARY: This integrated forest vegetation management project... comments to Gallatin National Forest, Attn: Lonesome Wood Vegetation Management Project 2, Bozeman Ranger...

Proceedings-symposium on whitebark pine ecosystems: Ecology and management of a high-mountain resource; 1989 March 29-31; Bozeman, MT

Treesearch

Wyman C. Schmidt; Kathy J. McDonald

1990-01-01

Includes 52 papers and 14 poster synopses that present current knowledge about ecosystems where whitebark pine and associated flora and fauna predominate. This was the first symposium to explore the ecology and management of these ecosystems, which are becoming increasingly important.

Proceedings of the 15th wildland shrub symposium; June 17-19, 2008; Bozeman, MT

Treesearch

Carl L. Wambolt; Stanley G. Kitchen; Michael R. Fisina; Bok Sowell; Richard B. Keigley; Patsy Palacios; Jill Robinson

2011-01-01

The 35 papers in this proceedings are divided into four sections; the first includes an introduction to the symposium theme of Shrublands as wildlands and wildlife habitat, along with keynote addresses discussing geographic affiliations of eastern Montana's "great Plains Flora" and methodology for surveying mule deer winter range habitat use and...

Small Business Innovations (Crystal Components)

NASA Technical Reports Server (NTRS)

1991-01-01

Scientific Materials Corporation, Bozeman, MT developed the SciMax line of improved Nd:Yag crystals under an Small Business Innovation Research (SBIR) contract with Langley Research Center. They reduced the amount of water trapped in the crystals during growth to improve the optical quality and efficiency. Applications of the crystals include fiber optics, telecommunications, welding, drilling, eye surgery and medical instrumentation.

76 FR 35098 - Standard Instrument Approach Procedures, and Takeoff Minimums and Obstacle Departure Procedures...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-16

... North Bend Southwest Rgnl...... 1/9838 5/2/11 RNAV (RNP) Z RWY 4, Orig 30-Jun-11 MT Bozeman Gallatin... City, OK. 73169 (Mail Address: P.O. Box 25082 Oklahoma City, OK 73125) telephone: (405) 954-4164... appropriate FAA Form 8260, as modified by the National Flight Data Center (FDC)/Permanent Notice to Airmen (P...

Oversight Hearings on the Rehabilitation Act. Hearing before the Subcommittee on Select Education of the Committee on Education and Labor, House of Representatives, Ninety-Ninth Congress, First Session (Washington, DC, June 11, June 25, and July 17; Bozeman, MT, August 27; and Honolulu, HI, November 26, 1985).

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Education and Labor.

The transcript of the 1985 House of Representatives hearings on reauthorization of the Rehabilitation Act of 1973 contains verbatim testimony and committee questions, prepared statements, letters, and supplemental material. Organizations providing testimony or statements include the following: Council of State Administrators of Vocational…

Out of the Lab...Into the Real World

NASA Technical Reports Server (NTRS)

1999-01-01

Big Sky Laser Technologies of Bozeman, MT is a developer of compact, ruggedized commercial and developmental laser systems, including small medical lasers and Lidars used in NASA tracking applications. Company engineers developing new laser products determined that NASA technology for detection and control of prelasing in a Q-switched laser would be of value to them in at least two of their product lines. Big Sky Laser's CFR-800 unit is based on NASA technology to which they obtained a non-exclusive patent.

Faculty Handbook -- 1974-1976. Montana State University, Bozeman.

ERIC Educational Resources Information Center

Montana State Univ., Bozeman.

The Montana State University's 1974 faculty handbook outlines the history and scope of the university within the Montana state higher education system. The document details the administrative organization; the faculty organization and operation; personnel policies including appointments, tenure, rank and titles, faculty review, promotions,…

Creating Educational Pathways: A Montana University Teams Up with Tribal Colleges.

ERIC Educational Resources Information Center

Trinity, Annette

1990-01-01

Describes programs at Montana State University, Bozeman, that cooperate with tribally controlled community colleges to provide opportunities for American Indian transfer students. Focuses on training in health sciences, engineering, public service, and educational administration and on efforts to ease students' transition to university life. (SV)

Bozeman Pass post-fencing wildlife monitoring.

DOT National Transportation Integrated Search

2010-12-01

The Bozeman Pass transportation corridor between Bozeman and Livingston, Montana, includes Interstate 90 (I-90), frontage roads, : and a railroad. The highway was a suspected barrier and hazard to animal movement in the Bozeman Pass area, which is co...

Reauthorization of the Discretionary Programs under the Education of the Handicapped Act. Hearings before the Subcommittee on Select Education of the Committee on Education and Labor. House of Representatives, Ninety-Ninth Congress, First Session (Bozeman, MT, August 27; Washington, DC, October 22-23; and Honolulu, HI, November 26, 1985).

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Education and Labor.

The transcript of the 1985 hearings contains testimony and prepared statements on reauthorization of the discretionary programs under P.L. 94-142, the Education for All Handicapped Children Act (Part B of the Education of the Handicapped Act). The discretionary programs section of the law authorizes federal assistance to support such programs as…

A Response to "A Description of Merger Applied to the Montana State University Context."

ERIC Educational Resources Information Center

Sexton, Ronald P.; And Others

1996-01-01

Contains three responses to Stephen L. Coffman's article appearing in the same issue, "A Description of Merger Applied to the Montana State University Context": one from the chancellor of Montana State University-Billings, one from the president of Montana State University-Bozeman, and one from the commissioner of the Montana State University…

Annual Report to the Board of Regents of the Montana University System, 1973-74.

ERIC Educational Resources Information Center

Montana Univ. System, Helena.

This is the first annual report to the Board of Regents from the Commissioner of Higher Education. The purpose of the report is to provide the Board of Regents with comprehensive information on programs and policies of the six institutions of the Montana University System: University of Montana at Missoula, Montana State University at Bozeman,…

Following Their Dreams: Native American Students Pursuing Medical School.

ERIC Educational Resources Information Center

Boswell, Evelyn

1997-01-01

Four Native American first-year medical school students from Montana discuss their career choice and their goals for establishing medical practices in Native American communities. A regional program has enabled the students to take their first year of classes at Montana State University-Bozeman and to complete their studies at the University of…

Academic Success of Suspended Students. AIR 2001 Annual Forum Paper.

ERIC Educational Resources Information Center

Howard, Richard D.; Borland, Ken; Johnson, Cel; Baker, Larry J.

Cohorts of entering freshmen were tracked over time to determine whether the suspension policy at Montana State University (MSU), Bozeman was having the intended effect on academic success, defined as degree completion. The university's current policy requires students to be suspended after receiving grade point averages (GPAs) of lower than 2.00…

American Indian Education Option in the Elementary Teacher Training Program at Montana State University at Bozeman.

ERIC Educational Resources Information Center

Old Coyote, Elnora A.; Chesarek, John Stephen

A description of the history and development of the University of Montana's American Indian education option in elementary teacher education is presented. Objectives and goals for the federally funded project are given, and the core personnel involved in the program are introduced. Budgeting procedures for the implementation of the option are…

Collaborative Inquiry into a Partnership Community.

ERIC Educational Resources Information Center

Noel, Jana R.

1996-01-01

Describes a school/college partnership between the Bozeman (Montana) School District and the Montana State University, concentrating on the program documenter's role in critical analysis. The documenter helps a partnership community by summarizing activities, providing a contextual framework for activities, encouraging completion of the…

Reflections on Tribal Governance in Montana.

ERIC Educational Resources Information Center

Weaver, Kenneth L., Ed.

This document discusses tribal governance as part of the "Native American Week" on Montana State University's Bozeman campus. The document contains a commissioned paper, a panel discussion, a speech, and a list of legal documents of tribal governments in Montana. The commissioned paper, "Federal Indian Policy: A Summary," by…

Promoting U.S. Census Data in an Academic Environment: Opportunities and Challenges.

ERIC Educational Resources Information Center

Ragains, Patrick

1995-01-01

Discusses efforts at the Montana State University (Bozeman) library to promote use of census data. Describes instructional sessions, and budgetary and service issues faced by depository libraries providing access to census data in electronic formats. Also includes copies of handouts from the instructional sessions. (Author/AEF)

A Model Instructional Computing Course for Preservice Teachers.

ERIC Educational Resources Information Center

Cimikowski, Linda; Cook, Joan

Foundations of Instructional Computing is a required one-semester, two credit course in the Education Department of Montana State University (Bozeman). The major objective of the course is to help preservice teachers develop use of computer technology that is confident, thoughtful, and integrated into their individual teaching philosophy and…

Approaches to Changing the Physical Attributes of the Adult Learning Environment: A Preliminary Investigation.

ERIC Educational Resources Information Center

Fulton, Rodney D.

A study surveyed 139 individuals to determine if differences in the way they approached the physical attributes of various learning environments could be attributed to either gender or age. Participants were Montana State University graduate students in education; adult basic education students in Bozeman, Montana; adult basic education faculty…

A shallow subsurface controlled release facility in Bozeman, Montana, USA, for testing near surface CO2 detection techniques and transport models

USGS Publications Warehouse

Spangler, L.H.; Dobeck, L.M.; Repasky, K.S.; Nehrir, A.R.; Humphries, S.D.; Keith, C.J.; Shaw, J.A.; Rouse, J.H.; Cunningham, A.B.; Benson, S.M.; Oldenburg, C.M.; Lewicki, J.L.; Wells, A.W.; Diehl, J.R.; Strazisar, B.R.; Fessenden, J.E.; Rahn, T.A.; Amonette, J.E.; Barr, J.L.; Pickles, W.L.; Jacobson, J.D.; Silver, E.A.; Male, E.J.; Rauch, H.W.; Gullickson, K.S.; Trautz, R.; Kharaka, Y.; Birkholzer, J.; Wielopolski, L.

2010-01-01

A controlled field pilot has been developed in Bozeman, Montana, USA, to study near surface CO2 transport and detection technologies. A slotted horizontal well divided into six zones was installed in the shallow subsurface. The scale and CO2 release rates were chosen to be relevant to developing monitoring strategies for geological carbon storage. The field site was characterized before injection, and CO2 transport and concentrations in saturated soil and the vadose zone were modeled. Controlled releases of CO2 from the horizontal well were performed in the summers of 2007 and 2008, and collaborators from six national labs, three universities, and the U.S. Geological Survey investigated movement of CO2 through the soil, water, plants, and air with a wide range of near surface detection techniques. An overview of these results will be presented. ?? 2009 The Author(s).

Evaluation of Personal Response Systems from a Teaching Perspective

ERIC Educational Resources Information Center

Dailey, Rocky Allan

2012-01-01

The purpose of this qualitative transcendental phenomenological study was to examine the usage, attitudes, and perceptions of personal response system (PRS) use by teaching faculty who had used the technology in at least one course at Montana State University (MSU) in Bozeman in the past six years. Fifteen faculty members who had used PRS in their…

Proceedings of the 1984 Conference on Outdoor Recreation: A Landmark Conference in the Outdoor Recreation Field (1st, Bozeman, Montana, November 1-4, 1984).

ERIC Educational Resources Information Center

Miles, John C., Ed.; Watters, Ron, Ed.

This document consists of materials presented at a conference organized by representatives of university outdoor programs to discuss issues and exchange ideas about outdoor topics. Twenty-six papers were presented: (1) "Conference on Outdoor Recreation for the Disabled: Breaking the Stereotype" (Tom Whittaker and Sheila Brashear); (2)…

Data Rights for Science and Technology Projects

DTIC Science & Technology

2014-04-01

disclose the data. Conversely, the data may be withheld from delivery or specified via form, fit, and function information only ( Bozeman , 2000). These...Processes, 163(9), 41–43. Retrieved from http:// search.ebscohost.com/login.aspx?direct=true&db=a9h&AN=18215906& site=ehost-live Bozeman , B. (2000

Can You Hear Us Now? A White Paper on Connecting Minority-Serving Institutions in the West to U.S. Advanced Cyberinfrastructure. Lariat Summit on Minority Institutions and Cyberinfrastructure in the West (Bozeman, Montana, August 14-15, 2006)

ERIC Educational Resources Information Center

Fox, Louis

2007-01-01

Advanced information, communication, computation and collaboration technologies, known as "cyberinfrastructure," have become essential elements for research, education, and innovation in the 21st century. A major challenge confronting the United States today is how to ensure that all colleges and universities, including those that have…

The Montana ALE (Autonomous Lunar Excavator) Systems Engineering Report

NASA Technical Reports Server (NTRS)

Hull, Bethanne J.

2012-01-01

On May 2 1-26, 20 12, the third annual NASA Lunabotics Mining Competition will be held at the Kennedy Space Center in Florida. This event brings together student teams from universities around the world to compete in an engineering challenge. Each team must design, build and operate a robotic excavator that can collect artificial lunar soil and deposit it at a target location. Montana State University, Bozeman, is one of the institutions selected to field a team this year. This paper will summarize the goals of MSU's lunar excavator project, known as the Autonomous Lunar Explorer (ALE), along with the engineering process that the MSU team is using to fulfill these goals, according to NASA's systems engineering guidelines.

On transferring the grid technology to the biomedical community.

PubMed

Mohammed, Yassene; Sax, Ulrich; Dickmann, Frank; Lippert, Joerg; Solodenko, Juri; von Voigt, Gabriele; Smith, Matthew; Rienhoff, Otto

2010-01-01

Natural scientists such as physicists pioneered the sharing of computing resources, which resulted in the Grid. The inter domain transfer process of this technology has been an intuitive process. Some difficulties facing the life science community can be understood using the Bozeman's "Effectiveness Model of Technology Transfer". Bozeman's and classical technology transfer approaches deal with technologies that have achieved certain stability. Grid and Cloud solutions are technologies that are still in flux. We illustrate how Grid computing creates new difficulties for the technology transfer process that are not considered in Bozeman's model. We show why the success of health Grids should be measured by the qualified scientific human capital and opportunities created, and not primarily by the market impact. With two examples we show how the Grid technology transfer theory corresponds to the reality. We conclude with recommendations that can help improve the adoption of Grid solutions into the biomedical community. These results give a more concise explanation of the difficulties most life science IT projects are facing in the late funding periods, and show some leveraging steps which can help to overcome the "vale of tears".

Reaching for the cloud: on the lessons learned from grid computing technology transfer process to the biomedical community.

PubMed

Mohammed, Yassene; Dickmann, Frank; Sax, Ulrich; von Voigt, Gabriele; Smith, Matthew; Rienhoff, Otto

2010-01-01

Natural scientists such as physicists pioneered the sharing of computing resources, which led to the creation of the Grid. The inter domain transfer process of this technology has hitherto been an intuitive process without in depth analysis. Some difficulties facing the life science community in this transfer can be understood using the Bozeman's "Effectiveness Model of Technology Transfer". Bozeman's and classical technology transfer approaches deal with technologies which have achieved certain stability. Grid and Cloud solutions are technologies, which are still in flux. We show how Grid computing creates new difficulties in the transfer process that are not considered in Bozeman's model. We show why the success of healthgrids should be measured by the qualified scientific human capital and the opportunities created, and not primarily by the market impact. We conclude with recommendations that can help improve the adoption of Grid and Cloud solutions into the biomedical community. These results give a more concise explanation of the difficulties many life science IT projects are facing in the late funding periods, and show leveraging steps that can help overcoming the "vale of tears".

Celebrating Einstein

NASA Astrophysics Data System (ADS)

Key, Joey; Yunes, Nicolas

2013-04-01

The Gravity Group at Montana State University (MSU) hosted Celebrating Einstein, a free public arts and multimedia event celebrating Einstein and his ideas in Bozeman, Montana April 2-6, 2013. The products of our efforts are now available to any party interested in hosting a similar event. Celebrating Einstein is a truly interdisciplinary effort including art, film, dance, music, physics, history, and education. Events included a black hole immersive art installation, a series of public talks by physicists, and Einstein lessons in the public schools leading up to a live free public multimedia performance including a professional dance company, a live interview with a renowned physicist, and an original score composed for the MSU student symphony to be performed with an original film produced by the Science and Natural History film program at MSU. This project is funded by the Montana Space Grant Consortium, Montana State University, and the National Science Foundation.

Multi-channel Auto-dilution System for Remote Continuous Monitoring of High Soil-CO2 Fluxes

NASA Astrophysics Data System (ADS)

Barr, J. L.; Amonette, J. E.

2008-12-01

We describe a novel field instrument that takes input from up to 27 soil flux chambers and measures flux using the steady-state method. CO2 concentrations are determined with an infrared gas analyzer (IRGA, 0- 3000 ppmv range) with corrections for temperature, barometric pressure, and moisture content. The concentrations are monitored during data collection and, if they exceed the range of the IRGA, a stepped dilution program is automatically implemented that allows up to 50-fold dilution of the incoming gas stream with N2 supplied by boil-off from a large dewar. The upper concentration limit of the system with dilution is extended to at least 150,000 ppmv CO2. The data are stored on a datalogger having a cellular modem connection that allows remote control of the system as well as transmittal of data. The system is designed to operate for six weeks with no on-site maintenance required. Longer periods are possible with modifications to allow on-site generation of N2 from air. Example data from a recent CO2 test injection at the Zero- Emission Research and Technology (ZERT) field site in Bozeman, MT are presented.

75 FR 58430 - Notice of Inventory Completion: University of Montana, Missoula, MT

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... DEPARTMENT OF THE INTERIOR National Park Service Notice of Inventory Completion: University of... University of Montana, Missoula, MT. The human remains and associated funerary object were removed from a... made by University of Montana, Department of Anthropology, professional staff in consultation with...

77 FR 42509 - Notice of Inventory Completion: The University of Montana, Missoula, MT

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-19

... Thompson, Department of Anthropology, University of Montana, Missoula, MT 59812, telephone (406) 243-5525... over to the University of Montana, Department of Anthropology. The remains were discovered in the... White, contacted Carling Malouf of the University of Montana, Department of Anthropology, and the...

77 FR 74873 - Notice of Inventory Completion: University of Montana, Missoula, MT; Museum of the Rockies at...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-18

... Inventory Completion: University of Montana, Missoula, MT; Museum of the Rockies at Montana State University... Service, Interior. ACTION: Notice. SUMMARY: The University of Montana, the Museum of the Rockies at... contact the University of Montana, which is acting on its own behalf and for the Museum of the Rockies and...

75 FR 45658 - Notice of Inventory Completion: Museum of Cultural and Natural History, Central Michigan...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... Cultural and Natural History, Central Michigan University, Mt. Pleasant, MI; Correction AGENCY: National... Natural History, Central Michigan University, Mt. Pleasant, MI. The human remains and associated funerary... History professional staff and physical anthropologists from Western Michigan University, Kalamazoo, MI...

Bozeman Pass wildlife channelization ITS project.

DOT National Transportation Integrated Search

2006-06-01

Animal-vehicle collisions (AVCs) are a growing concern as vehicle miles traveled and human encroachment into wildlife habitat : continues to increase throughout the United States. Few studies have examined the application of intelligent transportatio...

Bozeman Pass wildlife channelization ITS project : executive summary.

DOT National Transportation Integrated Search

2006-05-31

Animal-vehicle collisions (AVCs) are a growing concern as vehicle miles traveled and : human encroachment into wildlife habitat continues to increase throughout the United : States. Measures to prevent AVCs such as wildlife exclusion fencing and wild...

77 FR 43116 - Notice of Inventory Completion: The University of Montana, Missoula, MT; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-23

... and associated funerary objects in the possession of The University of Montana, Missoula, MT. The human remains and associated funerary objects were removed from various locations in western Montana... objects. The National Park Service is not responsible for the determinations in this notice. This notice...

Taming a wandering attention: short-form mindfulness training in student cohorts.

PubMed

Morrison, Alexandra B; Goolsarran, Merissa; Rogers, Scott L; Jha, Amishi P

2014-01-06

Mindfulness training (MT) is a form of mental training in which individuals engage in exercises to cultivate an attentive, present centered, and non-reactive mental mode. The present study examines the putative benefits of MT in University students for whom mind wandering can interfere with learning and academic success. We tested the hypothesis that short-form MT (7 h over 7 weeks) contextualized for the challenges and concerns of University students may reduce mind wandering and improve working memory. Performance on the sustained attention to response task (SART) and two working memory tasks (operation span, delayed-recognition with distracters) was indexed in participants assigned to a waitlist control group or the MT course. Results demonstrated MT-related benefits in SART performance. Relative to the control group, MT participants had higher task accuracy and self-reported being more "on-task" after the 7-week training period. MT did not significantly benefit the operation span task or accuracy on the delayed-recognition task. Together these results suggest that while short-form MT did not bolster working memory task performance, it may help curb mind wandering and should, therefore, be further investigated for its use in academic contexts.

The Story of Story Mill-A Montana Community Working to Restore Wetlands

EPA Pesticide Factsheets

Story Mill, a 55-acre site on the outskirts of Bozeman, Montana, has undergone several transformations in recent history. The place is virtually a “mill of stories” with respect to land use, but originally it was a wetland.

77 FR 64334 - Environmental Impacts Statements; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-19

..., Jack Rabbit to Big Sky Meadow Village 161 kV Transmission Line Upgrade, Bozeman Ranger District..., Lakewood Southeast Project, Proposes to Manage Vegetation and Habitat, Lakewood-Laona Ranger District... Interchange Project, Improvements, Solano County, CA, Review Period Ends: 11/19/2012, Contact: Melanie Brent...

Assessing human metal accumulations in an urban superfund site.

PubMed

Hailer, M Katie; Peck, Christopher P; Calhoun, Michael W; West, Robert F; James, Kyle J; Siciliano, Steven D

2017-09-01

Butte, Montana is part of the largest superfund site in the continental United States. Open-pit mining continues in close proximity to Butte's urban population. This study seeks to establish baseline metal concentrations in the hair and blood of individuals living in Butte, MT and possible routes of exposure. Volunteers from Butte (n=116) and Bozeman (n=86) were recruited to submit hair and blood samples and asked to complete a lifestyle survey. Elemental analysis of hair and blood samples was performed by ICP-MS. Three air monitors were stationed in Butte to collect particulate and filters were analyzed by ICP-MS. Soil samples from the yards of Butte volunteers were quantified by ICP-MS. Hair analysis revealed concentrations of Al, As, Cd, Cu, Mn, Mo, and U to be statistically elevated in Butte's population. Blood analysis revealed that the concentration of As was also statistically elevated in the Butte population. Multiple regression analysis was performed for the elements As, Cu, and Mn for hair and blood samples. Soil samples revealed detectable levels of As, Pb, Cu, Mn, and Cd, with As and Cu levels being higher than expected in some of the samples. Air sampling revealed consistently elevated As and Mn levels in the larger particulate sampled as compared to average U.S. ambient air data. Copyright © 2017 Elsevier B.V. All rights reserved.

Construct Validity of the MMPI-2 College Maladjustment (Mt) Scale

ERIC Educational Resources Information Center

Barthlow, Deanna L.; Graham, John R.; Ben-Porath, Yossef S.; McNulty, John L

2004-01-01

The construct validity of the MMPI-2 (Minnesota Multiphasic Personality Inventory-2) College Maladjustment (Mt) Scale was examined using 376 student clients at a university psychological clinic. A principal components analysis and correlations of Mt scale scores with clients' and therapists' ratings of symptoms and functioning showed that the Mt…

District-Owned vs Contracted Bus Service.

ERIC Educational Resources Information Center

Lehman, Tom; Harkin, Gary

1979-01-01

A synopsis of the results of a study conducted for the Bozeman, Montana, Public Schools. The study evaluated the feasibility of a district-owned vs a contracted pupil transportation system. Various aspects of school transportation were analyzed by their relationship to safety, control, service, and cost. (Author/MLF)

Report of Ninth Biennial Conference on Chemical Education.

ERIC Educational Resources Information Center

Journal of Chemical Education, 1987

1987-01-01

Provides a summary of the events occurring at the Ninth Biennial Conference on Chemical Education, held in Bozeman, Montana, on July 27-August 2, 1986. Contains brief descriptions of sessions on the role of chemists, demonstrations of laboratory experiences, learning chemistry with computers, teacher training, and chemistry for elementary school…

Use of a School Referendum to Deter Teen-Age Tobacco Use.

ERIC Educational Resources Information Center

Males, Mike

1992-01-01

Montana's school tobacco referendum includes youth in decisions regarding tobacco and health, demonstrating peer disapproval of tobacco use. The referendum, which asked students whether vendors should refuse tobacco sales to minors, follows the example of the Bozeman, Montana, school district in which secondary students and staff supported tobacco…

Human Resource Management, Computers, and Organization Theory.

ERIC Educational Resources Information Center

Garson, G. David

In an attempt to provide a framework for research and theory building in public management information systems (PMIS), state officials responsible for computing in personnel operations were surveyed. The data were applied to hypotheses arising from a recent model by Bozeman and Bretschneider, attempting to relate organization theory to management…

Biennial Conference on Chemical Education: Abstracts of Papers (9th, Bozeman, Montana, July 27-August 2, 1986).

ERIC Educational Resources Information Center

1986

This document includes summaries of conference presentations dealing with a wide variety of topics, including chemistry units for the elementary classroom, science experimentation in the secondary school, computer simulations, computer interfaces, videodisc technology, correspondence teaching of general chemistry, interdisciplinary energy courses,…

Acute Effects of an Alternative Electronic-Control-Device Waveform in Swine

DTIC Science & Technology

2009-03-01

sequences in a normal individual. Bozeman [32] suggested that lethality due to ECD impact could be due to hyperkalemia related to muscle contraction...and our previous investigations [1, 2], there may be a wide margin of safety, relative to hyperkalemia , for most ECD applications. The increase in

Functional and nutritional characteristics of wheat grown in organic and conventional cropping systems

USDA-ARS?s Scientific Manuscript database

The effects of organic vs. conventional farming practices on wheat functional and nutritional characteristics were compared. Soft white winter wheat and hard red spring wheat were obtained from long-term replicated field plots near Pullman, Washington and Bozeman, Montana. Test weight, kernel weight...

A test of the transcription model for biased inheritance of yeast mitochondrial DNA.

PubMed

Lorimer, H E; Brewer, B J; Fangman, W L

1995-09-01

Two strand-specific origins of replication appear to be required for mammalian mitochondrial DNA (mtDNA) replication. Structural equivalents of these origins are found in the rep sequences of Saccharomyces cerevisiae mtDNA. These striking similarities have contributed to a universal model for the initiation of mtDNA replication in which a primer is created by cleavage of an origin region transcript. Consistent with this model are the properties of deletion mutants of yeast mtDNA ([rho-]) with a high density of reps (HS [rho-]). These mutant mtDNAs are preferentially inherited by the progeny resulting from the mating of HS [rho-] cells with cells containing wild-type mtDNA ([rho+]). This bias is presumed to result from a replication advantage conferred on HS [rho-] mtDNA by the high density of rep sequences acting as origins. To test whether transcription is indeed required for the preferential inheritance of HS [rho-] mtDNA, we deleted the nuclear gene (RPO41) for the mitochondrial RNA polymerase, reducing transcripts by at least 1000-fold. Since [rho-] genomes, but not [rho+] genomes, are stable when RPO41 is deleted, we examined matings between HS [rho-] and neutral [rho-] cells. Neutral [rho-] mtDNAs lack rep sequences and are not preferentially inherited in [rho-] x [rho+] crosses. In HS [rho-] x neutral [rho-] matings, the HS [rho-] mtDNA was preferentially inherited whether both parents were wild type or both were deleted for RPO41. Thus, transcription from the rep promoter does not appear to be necessary for biased inheritance. Our results, and analysis of the literature, suggest that priming by transcription is not a universal mechanism for mtDNA replication initiation.

MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features

PubMed Central

Li, Xiaoran; Zhong, Yali; Lu, Jie; Axcrona, Karol; Eide, Lars; Syljuåsen, Randi G.; Peng, Qian; Wang, Junbai; Zhang, Hongquan; Goscinski, Mariusz Adam; Kvalheim, Gunnar; Nesland, Jahn M.; Suo, Zhenhe

2016-01-01

Reducing mtDNA content was considered as a critical step in the metabolism restructuring for cell stemness restoration and further neoplastic development. However, the connections between mtDNA depletion and metabolism reprograming-based cancer cell stemness in prostate cancers are still lack of studies. Here, we demonstrated that human CRPC cell line PC3 tolerated high concentration of the mtDNA replication inhibitor ethidium bromide (EtBr) and the mtDNA depletion triggered a universal metabolic remodeling process. Failure in completing that process caused lethal consequences. The mtDNA depleted (MtDP) PC3 cells could be steadily maintained in the special medium in slow cycling status. The MtDP PC3 cells contained immature mitochondria and exhibited Warburg effect. Furthermore, the MtDP PC3 cells were resistant to therapeutic treatments and contained greater cancer stem cell-like subpopulations: CD44+, ABCG2+, side-population and ALDHbright. In conclusion, these results highlight the association of mtDNA content, mitochondrial function and cancer cell stemness features. PMID:27248169

Storymakers: Hopa Mountain's Early Literacy Program

ERIC Educational Resources Information Center

Templin, Patricia A.

2013-01-01

Hopa Mountain's StoryMakers program is an innovative, research-based program for donating high quality young children's books to parents. Hopa Mountain is a nonprofit organization based in Bozeman, Montana. Hopa Mountain works with groups of rural and tribal citizen leaders who form StoryMakers Community Teams to talk one-on-one with local parents…

Public Value Mapping of Equity in Emerging Nanomedicine

ERIC Educational Resources Information Center

Slade, Catherine P.

2011-01-01

Public values failure occurs when the market and the public sector fail to provide goods and services required to achieve the core values of society such as equity (Bozeman 2007). That public policy for emerging health technologies should address intrinsic societal values such as equity is not a novel concept. However, the ways that the public…

Construct validity of the MMPI-2 College Maladjustment (Mt) Scale.

PubMed

Barthlow, Deanna L; Graham, John R; Ben-Porath, Yossef S; McNulty, John L

2004-09-01

The construct validity of the MMPI-2 (Minnesota Multiphasic Personality Inventory-2) College Maladjustment (Mt) Scale was examined using 376 student clients at a university psychological clinic. A principal components analysis and correlations of Mt scale scores with clients' and therapists' ratings of symptoms and functioning showed that the Mt scale identifies the presence of maladjustment as defined in terms of depressive and anxious symptoms. There is no evidence to show that the scale is specific to college students or that it is sensitive to severe psychological disturbance. The Mt scale does not inform the clinician as to why a person is distressed. In addition, there is no evidence from this study to suggest the superiority of the Mt scale over other MMPI-2 maladjustment measures. Therapists should use the entire MMPI-2 profile, not just the Mt scale, to gain the most comprehensive and specific understanding of clients.

PreliminaryEquatorial Paleomagnetic results from Mt Kenya lavas. Neil D Opdyke, 1, Dennis V Kent, 2, Kainian Huang ,1, J.P. Patel , 3

NASA Astrophysics Data System (ADS)

Opdyke, N. D.; Kent, D. V.; Huang, K.; Patel, J. P.

2007-12-01

Field work on this study was carried out in August of 2006 by field parties from the University of Florida and Rutgers University. Mt Kenya is believed to be Plio-Pleistocene in age and an Argon dating survey is underway Ten samples were taken at each site consisting of one exposure in individual lava Flows. These exposures are usually in road cuts, streambeds and in some cases roadbeds. We sampled 100 sites distributed around the Mt Kenya Massif and to the northeast along the Nyambini range. The equator bisex's Mt Kenya and all sites were sampled within 40" north or south of the equator . The samples were returned to the US and processed at the University of Florida paleomagnetic laboratory. Many sites were severely affected by lightning however after demagnetization 68 sites yielded directions with alpha 95's equal to or less than 10°. Normal magnetized sites dominate, with N=58 (Dec=1°,Inc -0.1°,α95=2.6°) whereas only 10 reverse sites(Dec. =181.9,Inc. .6°α 95=8°) were identified. The combined site mean direction is Dec=1.1°, Inc..= -0.2° and α 95=3.2°. This result is not significantly different from what is expected from the geocentric axial dipole. VGP's were calculated from each site and the dispersion is low with the ASD = 11° which is in agreement with model "G" of MacFadden and McElhinny .No transitional directions were identified . Quadrupole components are not resolved. 1 Department of geological Sciences, the University of Florida , 2 Dept of Geology, Rutgers University,3,dept of Physics ,The University of Nairobi

Clinical Gestalt and the Prediction of Massive Transfusion after Trauma

PubMed Central

Pommerening, Matthew J.; Goodman, Michael D.; Holcomb, John B.; Wade, Charles E.; Fox, Erin E.; del Junco, Deborah J.; Brasel, Karen J.; Bulger, Eileen M.; Cohen, Mitch J.; Alarcon, Louis H.; Schreiber, Martin A.; Myers, John G.; Phelan, Herb A.; Muskat, Peter; Rahbar, Mohammad; Cotton, Bryan A.

2016-01-01

Introduction Early recognition and treatment of trauma patients requiring massive transfusion (MT) has been shown to reduce mortality. While many risk factors predicting MT have been demonstrated, there is no universally accepted method or algorithm to identify these patients. We hypothesized that even among experienced trauma surgeons, the clinical gestalt of identifying patients who will require MT is unreliable. Methods Transfusion and mortality outcomes after trauma were observed at 10 U.S. Level-1 trauma centers in patients who survived ≥30 minutes after admission and received ≥1 unit of RBC within 6 hours of arrival. Subjects who received ≥ 10 units within 24 hours of admission were classified as MT patients. Trauma surgeons were asked the clinical gestalt question “Is the patient likely to be massively transfused?” ten minutes after the patients arrival. The performance of clinical gestalt to predict MT was assessed using chi-square tests and ROC analysis to compare gestalt to previously described scoring systems. Results Of the 1,245 patients enrolled, 966 met inclusion criteria and 221 (23%) patients received MT. 415 (43%) were predicted to have a MT and 551(57%) were predicted to not have MT. Patients predicted to have MT were younger, more often sustained penetrating trauma, had higher ISS scores, higher heart rates, and lower systolic blood pressures (all p < 0.05). Gestalt sensitivity was 65.6% and specificity was 63.8%. PPV and NPV were 34.9% and 86.2% respectively. Conclusion Data from this large multicenter trial demonstrates that predicting the need for MT continues to be a challenge. Because of the increased mortality associated with delayed therapy, a more reliable algorithm is needed to identify and treat these severely injured patients earlier. Level of Evidence II; Diagnostic study - Development of diagnostic criteria on basis of consecutive patients (with universally applied reference standard) PMID:25682314

76 FR 27914 - Television Broadcasting Services; Kalispell, MT

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [MB Docket No. 11-20; RM-11619, DA 11-750] Television Broadcasting Services; Kalispell, MT AGENCY: Federal Communications Commission. ACTION: Final rule... rulemaking filed by Montana State University (``MSU'') requesting that channel *46 be transferred from the...

KSC-2015-1222

NASA Image and Video Library

2015-01-28

VANDENBERG AIR FORCE BASE, Calif. – From left, John Bellardo, co-principal investigator Cubesat at California Polytechnic, San Luis Obispo, David Rider, GRIFEX principal investigator at Jet Propulsion Laboratory, Pasadena, California, and Dave Klumpar, Firebird-II principal investigator and director of the Space Science and Engineering Laboratory at Montana State University in Bozeman, Montana, discuss three Educational Launch of Nanosatellites ELaNa CubeSat that are being flown as auxiliary payloads on NASA's Soil Moisture Active Passive mission, or SMAP, with the audience of a NASA Social held for at Vandenberg Air Force Base in California. This NASA Social brought together mission scientists and engineers with an audience of 70 students, educators, social media managers, bloggers, photographers and videographers who were selected from a pool of 325 applicants from 45 countries to participate in launch activities and communicate their experience with social media followers. The SMAP mission is scheduled to launch from Vandenberg on Jan. 29. To learn more about SMAP, visit http://www.nasa.gov/smap. Photo credit: NASA/Kim Shiflett

From Threshers to Thrashers: In Montana, 4-H Takes a Modern Spin To Engage "Blue-Ribbon Kids."

ERIC Educational Resources Information Center

Linik, Joyce Riha

2002-01-01

A 4-H skateboard club in Bozeman, Montana offers kids community service and educational opportunities as well as something to do after school. Adult and college-student volunteers teach a skateboarding curriculum and help kids fix boards and design ramps. Club members have learned public speaking, fundraising, city planning, and civic involvement…

A Research Study to Determine the Effects of Early Keyboard Use upon Student Development in Occupational Keyboarding. Final Report of Research.

ERIC Educational Resources Information Center

Warwood, Byrdeen; And Others

Before students can use microcomputers effectively, they need keyboarding skills. A project was conducted in Montana to teach keyboarding to fourth-grade children using computer-assisted instruction. Two fourth-grade classes at Hawthorne Elementary School, Bozeman, Montana, participated in an 8-week, 32-session elementary keyboarding pilot…

77 FR 73310 - Technical Amendment to List of User Fee Airports: Addition of Bozeman Yellowstone International...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-10

..., local, and tribal governments, in the aggregate, or by the private sector, of $100 million or more in... that landing rights airport. Section 236 of Public Law 98-573 (the Trade and Tariff Act of 1984... airport and shall be in the amount equal to the expenses incurred by the Commissioner of CBP in providing...

Health-hazard evaluation report HETA 91-298-2182, Gibson Flatiron, Erica Shell Manufacturing, Bozeman, Montana

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCammon, C.S.

1992-02-01

In response to a request from the Montana State Health Department, an evaluation was undertaken of exposures to wood dust and lacquer vapors at the Gibson Flatiron/Erica Shell Manufacturing Companies (SIC-3931), Bozeman, Montana. Gibson Flatiron manufactured mandolins and banjoes. Erica Shell Manufacturing Company cuts and grinds abalone and other sea shells into small pieces to be used in designs inlayed into mandolins and banjos. Measured wood dust levels ranged from 0.8 to 32mg/cu m with an 8 hour time weighted average (TWA) of 1.2 to 30mg/cu m. Rib construction and assembly, and planing bulk ebony wood had TWA exposures abovemore » the OSHA permissible exposure limit of 5mg/cu m for wood dust. Application of dyes and finishes resulted in low exposures to acetone (67641), toluene (108883), xylene (1330207), and butyl-acetate (123864). No solvent air concentrations were above 10% of their respective PELs. The author concludes that a health hazard existed for exposure to wood dusts. The author recommends the establishment of a respiratory protection program and a hearing conservation program. Emergency egress routes should be marked in the buildings.« less

XML Storage for Magnetotelluric Transfer Functions: Towards a Comprehensive Online Reference Database

NASA Astrophysics Data System (ADS)

Kelbert, A.; Blum, C.

2015-12-01

Magnetotelluric Transfer Functions (MT TFs) represent most of the information about Earth electrical conductivity found in the raw electromagnetic data, providing inputs for further inversion and interpretation. To be useful for scientific interpretation, they must also contain carefully recorded metadata. Making these data available in a discoverable and citable fashion would provide the most benefit to the scientific community, but such a development requires that the metadata is not only present in the file but is also searchable. The most commonly used MT TF format to date, the historical Society of Exploration Geophysicists Electromagnetic Data Interchange Standard 1987 (EDI), no longer supports some of the needs of modern magnetotellurics, most notably accurate error bars recording. Moreover, the inherent heterogeneity of EDI's and other historic MT TF formats has mostly kept the community away from healthy data sharing practices. Recently, the MT team at Oregon State University in collaboration with IRIS Data Management Center developed a new, XML-based format for MT transfer functions, and an online system for long-term storage, discovery and sharing of MT TF data worldwide (IRIS SPUD; www.iris.edu/spud/emtf). The system provides a query page where all of the MT transfer functions collected within the USArray MT experiment and other field campaigns can be searched for and downloaded; an automatic on-the-fly conversion to the historic EDI format is also included. To facilitate conversion to the new, more comprehensive and sustainable, XML format for MT TFs, and to streamline inclusion of historic data into the online database, we developed a set of open source format conversion tools, which can be used for rotation of MT TFs as well as a general XML <-> EDI converter (https://seiscode.iris.washington.edu/projects/emtf-fcu). Here, we report on the newly established collaboration between the USGS Geomagnetism Program and the Oregon State University to gather and convert both historic and modern-day MT or related transfer functions into the searchable database at the IRIS DMC. The more complete and free access to these previously collected MT TFs will be of great value to MT scientists both in planning future surveys, and then to leverage the value of the new data at the inversion and interpretation stage.

XMAP215 is a microtubule nucleation factor that functions synergistically with the γ-tubulin ring complex.

PubMed

Thawani, Akanksha; Kadzik, Rachel S; Petry, Sabine

2018-05-01

How microtubules (MTs) are generated in the cell is a major question in understanding how the cytoskeleton is assembled. For several decades, γ-tubulin has been accepted as the universal MT nucleator of the cell. Although there is evidence that γ-tubulin complexes are not the sole MT nucleators, identification of other nucleation factors has proven difficult. Here, we report that the well-characterized MT polymerase XMAP215 (chTOG/Msps/Stu2p/Alp14/Dis1 homologue) is essential for MT nucleation in Xenopus egg extracts. The concentration of XMAP215 determines the extent of MT nucleation. Even though XMAP215 and the γ-tubulin ring complex (γ-TuRC) possess minimal nucleation activity individually, together, these factors synergistically stimulate MT nucleation in vitro. The amino-terminal TOG domains 1-5 of XMAP215 bind to αβ-tubulin and promote MT polymerization, whereas the conserved carboxy terminus is required for efficient MT nucleation and directly binds to γ-tubulin. In summary, XMAP215 and γ-TuRC together function as the principal nucleation module that generates MTs in cells.

Multiple ways to prevent transmission of paternal mitochondrial DNA for maternal inheritance in animals.

PubMed

Sato, Ken; Sato, Miyuki

2017-10-01

Mitochondria contain their own DNA (mtDNA). In most sexually reproducing organisms, mtDNA is inherited maternally (uniparentally); this type of inheritance is thus referred to as 'maternal (uniparental) inheritance'. Recent studies have revealed various mechanisms to prevent the transmission of sperm-derived paternal mtDNA to the offspring, thereby ensuring maternal inheritance of mtDNA. In the nematode Caenorhabditis elegans, paternal mitochondria and their mtDNA degenerate almost immediately after fertilization and are selectively degraded by autophagy, which is referred to as 'allophagy' (allogeneic [non-self] organelle autophagy). In the fruit fly Drosophila melanogaster, paternal mtDNA is largely eliminated by an endonuclease G-mediated mechanism. Paternal mitochondria are subsequently removed by endocytic and autophagic pathways after fertilization. In many mammals, including humans, paternal mitochondria enter fertilized eggs. However, the fate of paternal mitochondria and their mtDNA in mammals is still a matter of debate. In this review, we will summarize recent knowledge on the molecular mechanisms underlying the prevention of paternal mtDNA transmission, which ensures maternal mtDNA inheritance in animals. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Serum Metallothioneins in Childhood Tumours—A Potential Prognostic Marker

PubMed Central

Kruseova, Jarmila; Hynek, David; Adam, Vojtech; Kizek, Rene; Prusa, Richard; Hrabeta, Jan; Eckschlager, Tomas

2013-01-01

Metallothioneins (MT) are low molecular weight, cysteine-rich proteins maintaining metal ions homeostasis. They play a role in carcinogenesis and may also cause chemoresistance. The aim of the study was to explore the importance of MT serum levels in children suffering from malignant tumours. This prospective study involves examination of 865 samples from 172 patients with malignant tumours treated from 2008 to 2011 at University Hospital Motol. MT serum levels were determined using differential pulse voltammetry–Brdicka reaction. Mean MT level was 2.7 ± 0.5 μM. There was no statistically significant difference between MT levels in different tumours. We also did not find any correlation between MT levels and response to therapy or clinical stages. However, we found a positive correlation between MT levels and age (p = 0.009) and a negative correlation with absolute lymphocyte number (p = 0.001). The fact that patients who had early disease recurrence had lower MT levels during the treatment (complete remission 2.67 vs. recurring 2.34, p = 0.001) seems to be important for clinical practice. Accordingly we believe that there is benefit in further studies of serum MT levels in tumours. PMID:23743828

Google Mercury: The Launch of a New Planet

NASA Astrophysics Data System (ADS)

Hirshon, B.; Chapman, C. R.; Edmonds, J.; Goldstein, J.; Hallau, K. G.; Solomon, S. C.; Vanhala, H.; Weir, H. M.; Messenger Education; Public Outreach Epo Team

2010-12-01

The NASA MESSENGER mission’s Education and Public Outreach (EPO) Team, in cooperation with Google, Inc., has launched Google Mercury, an immersive new environment on the Google Earth platform. Google Mercury features hundreds of surface features, most of them newly revealed by the three flybys of the innermost planet by the MESSENGER spacecraft. As with Google Earth, Google Mercury is available on line at no cost. This presentation will demonstrate how our team worked with Google staff, features we incorporated, how games can be developed within the Google Earth platform, and how others can add tours, games, and other educational features. Finally, we will detail new enhancements to be added once MESSENGER enters into orbit about Mercury in March 2011 and begins sending back compelling images and other global data sets on a daily basis. The MESSENGER EPO Team comprises individuals from the American Association for the Advancement of Science (AAAS); Carnegie Academy for Science Education (CASE); Center for Educational Resources (CERES) at Montana State University (MSU) - Bozeman; National Center for Earth and Space Science Education (NCESSE); Johns Hopkins University Applied Physics Laboratory (JHU/APL); National Air and Space Museum (NASM); Science Systems and Applications, Inc. (SSAI); and Southwest Research Institute (SwRI). Screen shot of Google Mercury as a work in progress

Evaluation of Investments in Science, Technology and Innovation: Applying Scientific and Technical Human Capital Framework for Assessment of Doctoral Students in Cooperative Research Centers

ERIC Educational Resources Information Center

Leonchuk, Olena

2016-01-01

This dissertation builds on an alternative framework for evaluation of science, technology and innovation (STI) outcomes--the scientific & technical (S&T) human capital which was developed by Bozeman, Dietz and Gaughan (2001). At its core, this framework looks beyond simple economic and publication metrics and instead focuses on…

MtMAPKK4 is an essential gene for growth and reproduction of Medicago truncatula.

PubMed

Chen, Tao; Zhou, Bo; Duan, Liujian; Zhu, Hui; Zhang, Zhongming

2017-04-01

Mitogen-activated protein kinase (MAPK) cascades are universal signaling modules in eukaryotes, including yeasts, animals and plants. They are involved in responses to various biotic and abiotic stresses, hormones, cell division and developmental processes. A MAPK cascade is composed of three functionally tiered protein kinases, namely MAPK, MAPK kinases (MAPKKs) and MAPK kinase kinases (MAPKKKs). These kinases have been intensively studied for their roles in developmental and physiological processes in various organisms. In this study, a Medicago truncatula MtMAPKK4 mutant with the tobacco retrotransposon Tnt1 insertion was identified using reverse genetics methods. No homozygous progeny could be produced by self-pollination of mapkk4/+ heterozygotes for 5 generations. Heterozygous mapkk4/+ mutant plants exhibited growth retardation, chlorosis symptoms and significantly reduced numbers of infection threads and nodules. The interaction between MtMAPKK4 and MtMAPK3/6 occurred both in yeast and in planta. Green fluorescent protein-tagged MtMAPKK4, MtMAPK3 and MtMAPK6 were all localized to membranes, cytoplasm and nuclei. Expression of MtMAPKK4, MtMAPK3 and MtMAPK6 was detected in various tissues of M. truncatula plants at the nodule maturation stage. Transcript levels of these genes were decreased in roots at the early symbiotic stage. © 2016 Scandinavian Plant Physiology Society.

Deep sequencing shows that oocytes are not prone to accumulate mtDNA heteroplasmic mutations during ovarian ageing.

PubMed

Boucret, L; Bris, C; Seegers, V; Goudenège, D; Desquiret-Dumas, V; Domin-Bernhard, M; Ferré-L'Hotellier, V; Bouet, P E; Descamps, P; Reynier, P; Procaccio, V; May-Panloup, P

2017-10-01

Does ovarian ageing increase the number of heteroplasmic mitochondrial DNA (mtDNA) point mutations in oocytes? Our results suggest that oocytes are not subject to the accumulation of mtDNA point mutations during ovarian ageing. Ageing is associated with the alteration of mtDNA integrity in various tissues. Primary oocytes, present in the ovary since embryonic life, may accumulate mtDNA mutations during the process of ovarian ageing. This was an observational study of 53 immature oocyte-cumulus complexes retrieved from 35 women undergoing IVF at the University Hospital of Angers, France, from March 2013 to March 2014. The women were classified in two groups, one including 19 women showing signs of ovarian ageing objectified by a diminished ovarian reserve (DOR), and the other, including 16 women with a normal ovarian reserve (NOR), which served as a control group. mtDNA was extracted from isolated oocytes, and from their corresponding cumulus cells (CCs) considered as a somatic cell compartment. The average mtDNA content of each sample was assessed by using a quantitative real-time PCR technique. Deep sequencing was performed using the Ion Torrent Proton for Next-Generation Sequencing. Signal processing and base calling were done by the embedded pre-processing pipeline and the variants were analyzed using an in-house workflow. The distribution of the different variants between DOR and NOR patients, on one hand, and oocyte and CCs, on the other, was analyzed with the generalized mixed linear model to take into account the cluster of cells belonging to a given mother. There were no significant differences between the numbers of mtDNA variants between the DOR and the NOR patients, either in the oocytes (P = 0.867) or in the surrounding CCs (P = 0.154). There were also no differences in terms of variants with potential functional consequences. De-novo mtDNA variants were found in 28% of the oocytes and in 66% of the CCs with the mean number of variants being significantly different (respectively 0.321, SD = 0.547 and 1.075, SD = 1.158) (P < 0.0001). Variants with a potential functional consequence were also overrepresented in CCs compared with oocytes (P = 0.0019). N/A. Limitations may be due to the use of immature oocytes discarded during the assisted reproductive technology procedure, the small size of the sample, and the high-throughput sequencing technology that might not have detected heteroplasmy levels lower than 2%. The alteration of mtDNA integrity in oocytes during ovarian ageing is a recurring question to which our pilot study suggests a reassuring answer. This work was supported by the University Hospital of Angers, the University of Angers, France, and the French national research centers, INSERM and the CNRS. There are nocompeting interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Single Event Effect Testing of the Micron MT46V128M8

NASA Technical Reports Server (NTRS)

Stansberry, Scott; Campola, Michael; Wilcox, Ted; Seidleck, Christina; Phan, Anthony

2017-01-01

The Micron MT46V128M8 was tested for single event effects (SEE) at the Texas AM University Cyclotron Facility (TAMU) in June of 2017. Testing revealed a sensitivity to device hang-ups classified as single event functional interrupts (SEFI) and possible soft data errors classified as single event upsets (SEU).

Guidelines and Criteria to Assess Singing and Music Training in Baccalaureate Music Theater Programs

ERIC Educational Resources Information Center

Fleming-DeBerger, Rachelle

2011-01-01

Within the last twenty years there have been a growing number of prospective students interested in pursuing musical theater (MT) training in colleges and universities throughout the United States. To meet this demand, the number of schools offering baccalaureate MT degrees has also grown. However, information on how to assess the music and…

Association Between Chloroplast DNA and Mitochondrial DNA Haplotypes in Prunus spinosa L. (Rosaceae) Populations across Europe

PubMed Central

MOHANTY, APARAJITA; MARTÍN, JUAN PEDRO; GONZÁLEZ, LUIS MIGUEL; AGUINAGALDE, ITZIAR

2003-01-01

Chloroplast DNA (cpDNA) and mitochondrial DNA (mtDNA) were studied in 24 populations of Prunus spinosa sampled across Europe. The cpDNA and mtDNA fragments were amplified using universal primers and subsequently digested with restriction enzymes to obtain the polymorphisms. Combinations of all the polymorphisms resulted in 33 cpDNA haplotypes and two mtDNA haplotypes. Strict association between the cpDNA haplotypes and the mtDNA haplotypes was detected in most cases, indicating conjoint inheritance of the two genomes. The most frequent and abundant cpDNA haplotype (C20; frequency, 51 %) is always associated with the more frequent and abundant mtDNA haplotype (M1; frequency, 84 %). All but two of the cpDNA haplotypes associated with the less frequent mtDNA haplotype (M2) are private haplotypes. These private haplotypes are phylogenetically related but geographically unrelated. They form a separate cluster on the minimum‐length spanning tree. PMID:14534199

Atmospheric ions and germination of uredospores of Puccinia striiformis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharp, E.L.

1967-06-09

Atmospheric ions, identified by mobility characteristics, were associated with germination of lyophilized uredospores of Puccinia striiformis West. at Bozeman, Montana. Ions of intermediate size were highest in concentration, and percentage germination of spores was lowest during periods conducive to air pollution. In duplicate experiments at an isolated site near Barrow, Alaska, essentially all atmospheric ions were small ions and the fungus spores were consistently germinated near maximum.

Genome-Wide Identification of TCP Family Transcription Factors in Medicago truncatula Reveals Significant Roles of miR319-Targeted TCPs in Nodule Development

PubMed Central

Wang, Hongfeng; Wang, Hongwei; Liu, Rong; Xu, Yiteng; Lu, Zhichao; Zhou, Chuanen

2018-01-01

TCP proteins, the plant-specific transcription factors, are involved in the regulation of multiple aspects of plant development among different species, such as leaf development, branching, and flower symmetry. However, thus far, the roles of TCPs in legume, especially in nodulation are still not clear. In this study, a genome-wide analysis of TCP genes was carried out to discover their evolution and function in Medicago truncatula. In total, 21 MtTCPs were identified and classified into class I and class II, and the class II MtTCPs were further divided into two subclasses, CIN and CYC/TB1. The expression profiles of MtTCPs are dramatically different. The universal expression of class I MtTCPs was detected in all organs. However, the MtTCPs in CIN subclass were highly expressed in leaf and most of the members in CYC/TB1 subclass were highly expressed in flower. Such organ-specific expression patterns of MtTCPs suggest their different roles in plant development. In addition, most MtTCPs were down-regulated during the nodule development, except for the putative MtmiR319 targets, MtTCP3, MtTCP4, and MtTCP10A. Overexpression of MtmiR319A significantly reduced the expression level of MtTCP3/4/10A/10B and resulted in the decreased nodule number, indicating the important roles of MtmiR319-targeted MtTCPs in nodulation. Taken together, this study systematically analyzes the MtTCP gene family at a genome-wide level and their possible functions in nodulation, which lay the basis for further explorations of MtmiR319/MtTCPs module in association with nodule development in M. truncatula.

Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family.

PubMed

Kullar, Peter J; Gomez-Duran, Aurora; Gammage, Payam A; Garone, Caterina; Minczuk, Michal; Golder, Zoe; Wilson, Janet; Montoya, Julio; Häkli, Sanna; Kärppä, Mikko; Horvath, Rita; Majamaa, Kari; Chinnery, Patrick F

2018-01-01

The m.1555A>G mtDNA variant causes maternally inherited deafness, but the reasons for the highly variable clinical penetrance are not known. Exome sequencing identified a heterozygous start loss mutation in SSBP1, encoding the single stranded binding protein 1 (SSBP1), segregating with hearing loss in a multi-generational family transmitting m.1555A>G, associated with mtDNA depletion and multiple deletions in skeletal muscle. The SSBP1 mutation reduced steady state SSBP1 levels leading to a perturbation of mtDNA metabolism, likely compounding the intra-mitochondrial translation defect due to m.1555A>G in a tissue-specific manner. This family demonstrates the importance of rare trans-acting genetic nuclear modifiers in the clinical expression of mtDNA disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Altered mitochondrial genome content signals worse pathology and prognosis in prostate cancer.

PubMed

Kalsbeek, Anton M F; Chan, Eva K F; Grogan, Judith; Petersen, Desiree C; Jaratlerdsiri, Weerachai; Gupta, Ruta; Lyons, Ruth J; Haynes, Anne-Maree; Horvath, Lisa G; Kench, James G; Stricker, Phillip D; Hayes, Vanessa M

2018-01-01

Mitochondrial genome (mtDNA) content is depleted in many cancers. In prostate cancer, there is intra-glandular as well as inter-patient mtDNA copy number variation. In this study, we determine if mtDNA content can be used as a predictor for prostate cancer staging and outcomes. Fresh prostate cancer biopsies from 115 patients were obtained at time of surgery. All cores underwent pathological review, followed by isolation of cancer and normal tissue. DNA was extracted and qPCR performed to quantify the total amount of mtDNA as a ratio to genomic DNA. Differences in mtDNA content were compared for prostate cancer pathology features and disease outcomes. We showed a significantly reduced mtDNA content in prostate cancer compared with normal adjacent prostate tissue (mean difference 1.73-fold, P-value <0.001). Prostate cancer with increased mtDNA content showed unfavorable pathologic characteristics including, higher disease stage (PT2 vs PT3 P-value = 0.018), extracapsular extension (P-value = 0.02) and a trend toward an increased Gleason score (P-value = 0.064). No significant association was observed between changes in mtDNA content and biochemical recurrence (median follow up of 107 months). Contrary to other cancer types, prostate cancer tissue shows no universally depleted mtDNA content. Rather, the change in mtDNA content is highly variable, mirroring known prostate cancer genome heterogeneity. Patients with high mtDNA content have an unfavorable pathology, while a high mtDNA content in normal adjacent prostate tissue is associated with worse prognosis. © 2017 Wiley Periodicals, Inc.

A reduced number of mtSNPs saturates mitochondrial DNA haplotype diversity of worldwide population groups.

PubMed

Salas, Antonio; Amigo, Jorge

2010-05-03

The high levels of variation characterising the mitochondrial DNA (mtDNA) molecule are due ultimately to its high average mutation rate; moreover, mtDNA variation is deeply structured in different populations and ethnic groups. There is growing interest in selecting a reduced number of mtDNA single nucleotide polymorphisms (mtSNPs) that account for the maximum level of discrimination power in a given population. Applications of the selected mtSNP panel range from anthropologic and medical studies to forensic genetic casework. This study proposes a new simulation-based method that explores the ability of different mtSNP panels to yield the maximum levels of discrimination power. The method explores subsets of mtSNPs of different sizes randomly chosen from a preselected panel of mtSNPs based on frequency. More than 2,000 complete genomes representing three main continental human population groups (Africa, Europe, and Asia) and two admixed populations ("African-Americans" and "Hispanics") were collected from GenBank and the literature, and were used as training sets. Haplotype diversity was measured for each combination of mtSNP and compared with existing mtSNP panels available in the literature. The data indicates that only a reduced number of mtSNPs ranging from six to 22 are needed to account for 95% of the maximum haplotype diversity of a given population sample. However, only a small proportion of the best mtSNPs are shared between populations, indicating that there is not a perfect set of "universal" mtSNPs suitable for all population contexts. The discrimination power provided by these mtSNPs is much higher than the power of the mtSNP panels proposed in the literature to date. Some mtSNP combinations also yield high diversity values in admixed populations. The proposed computational approach for exploring combinations of mtSNPs that optimise the discrimination power of a given set of mtSNPs is more efficient than previous empirical approaches. In contrast to precedent findings, the results seem to indicate that only few mtSNPs are needed to reach high levels of discrimination power in a population, independently of its ancestral background.

Learner Resistance in Metacognition Training? An Exploration of Mismatches between Learner and Teacher Agendas

ERIC Educational Resources Information Center

Jing, Huang

2006-01-01

This paper examines how and why learner resistance (to the teacher's goals and expectations) occurred in a metacognition-training (MT) project, which aimed to enhance reflection and autonomy in EFL learning. MT was integrated into a regular EFL reading course for second-year BA TEFL undergraduates at a Chinese university. Learner resistance in the…

Mt. Druitt Early Childhood Project. Third, Fourth, and Fifth Annual Reports to Bernard Van Leer Foundation.

ERIC Educational Resources Information Center

Macquarie Univ., North Ryde (Australia). School of Education.

This series of the third, fourth, and fifth annual reports to the Bernard Van Leer Foundation on the Mt. Druitt Early Childhood Project of Macquarie University, Australia, describes the general activities, program developments, and research activities of the project for the period 1977-1979. The main objective of the project is to develop,…

Species Profiles: Life Histories and Environmental Requirements of Coastal Fishes and Invertebrates (South Atlantic): Bluefish

DTIC Science & Technology

1989-04-01

Invertebrates (South Atlantic) BLUEFISH AA I.,,bWU . . Coastal Ecology Group *Fish and Wildlife Service Waterways Experiment Station U.S. Department of the...Requirements of Coastal Fishes and Invertebrates (South Atlantic) BLUEFISH by J. Douglas Oliver, Michael J. Van Den Avyle, and Earl L. Bozeman, Jr. Georgia...Marine Fisheries Service, Panama City, Florida,for reviewing this manuscript. vi Figure 1. Bluefish . BLUEFISH NOMENCLATURE/TAXONOMY/RANGE westward to

Conflict, Culture, and History Regional Dimensions

DTIC Science & Technology

1993-01-01

actuality or the threat of civil and international war; the destinies of all peoples in the vast Southeast Asian region have long been molded by war, whether...denoting the embryo of a future Palestinian state . Each of these organizational types is mobile and fluid in the sense that it has ’no fixed territorial...time until a solution is reached . As Professor Bozeman observes, increasingly, movements claiming to be states in embryo , operating transnationally

Perception of the Professional Knowledge of and Education on the Medical Technology Products among the Pharmacists in the Baltic and Nordic Countries-A Cross-Sectional Exploratory Study.

PubMed

Volmer, Daisy; Sokirskaja, Aleksandra; Laaksonen, Raisa; Vainio, Kirsti; Sandler, Niklas; Halvorsen, Kjell H; Kjome, Reidun Lisbet Skeide; Gizurarson, Sveinbjörn; Muceniece, Ruta; Maurina, Baiba; Dauksiene, Jurgita; Ruuben, Lilian; Björnsdottir, Ingunn; Ratassepp, Tagne; Heinämäki, Jyrki

2016-10-13

With increased development of medical technology (MT), new challenges emerge related to education and training of pharmacists and other healthcare specialists. Currently, only a few universities in the EU promote MT education and research. The aim of this study was to evaluate the current status, views on, and need for the education on MT for the pharmacy students and practicing pharmacists in the Baltic and Nordic countries. The representatives of higher education institutions and community/hospital pharmacists from six Baltic and Nordic countries participated in a qualitative cross-sectional exploratory internet-based study from May to October 2014. Approximately two-third of the respondents considered professional knowledge about MT products important for pharmacists, but half of them had never participated in any MT courses. More practicing pharmacists than representatives of academia underlined the need for increased MT education for pharmacy students in the future. The pharmacists in the Baltic and Nordic countries consider the professional knowledge about MT as pertinent in their education and work. The limited number and status of MT courses available today, however, is a major concern among both pharmacy students and practicing pharmacists in these countries. In the future, increasing education combining theory and practice about MT products would be one possible solution to overcome this challenge.

Perception of the Professional Knowledge of and Education on the Medical Technology Products among the Pharmacists in the Baltic and Nordic Countries—A Cross-Sectional Exploratory Study

PubMed Central

Volmer, Daisy; Sokirskaja, Aleksandra; Laaksonen, Raisa; Vainio, Kirsti; Sandler, Niklas; Halvorsen, Kjell H.; Kjome, Reidun Lisbet Skeide; Gizurarson, Sveinbjörn; Muceniece, Ruta; Maurina, Baiba; Dauksiene, Jurgita; Ruuben, Lilian; Björnsdottir, Ingunn; Ratassepp, Tagne; Heinämäki, Jyrki

2016-01-01

With increased development of medical technology (MT), new challenges emerge related to education and training of pharmacists and other healthcare specialists. Currently, only a few universities in the EU promote MT education and research. Objectives: The aim of this study was to evaluate the current status, views on, and need for the education on MT for the pharmacy students and practicing pharmacists in the Baltic and Nordic countries. Methods: The representatives of higher education institutions and community/hospital pharmacists from six Baltic and Nordic countries participated in a qualitative cross-sectional exploratory internet-based study from May to October 2014. Results: Approximately two-third of the respondents considered professional knowledge about MT products important for pharmacists, but half of them had never participated in any MT courses. More practicing pharmacists than representatives of academia underlined the need for increased MT education for pharmacy students in the future. Conclusions: The pharmacists in the Baltic and Nordic countries consider the professional knowledge about MT as pertinent in their education and work. The limited number and status of MT courses available today, however, is a major concern among both pharmacy students and practicing pharmacists in these countries. In the future, increasing education combining theory and practice about MT products would be one possible solution to overcome this challenge. PMID:28970402

Evidence for double-strand break mediated mitochondrial DNA replication in Saccharomyces cerevisiae.

PubMed

Prasai, Kanchanjunga; Robinson, Lucy C; Scott, Rona S; Tatchell, Kelly; Harrison, Lynn

2017-07-27

The mechanism of mitochondrial DNA (mtDNA) replication in Saccharomyces cerevisiae is controversial. Evidence exists for double-strand break (DSB) mediated recombination-dependent replication at mitochondrial replication origin ori5 in hypersuppressive ρ- cells. However, it is not clear if this replication mode operates in ρ+ cells. To understand this, we targeted bacterial Ku (bKu), a DSB binding protein, to the mitochondria of ρ+ cells with the hypothesis that bKu would bind persistently to mtDNA DSBs, thereby preventing mtDNA replication or repair. Here, we show that mitochondrial-targeted bKu binds to ori5 and that inducible expression of bKu triggers petite formation preferentially in daughter cells. bKu expression also induces mtDNA depletion that eventually results in the formation of ρ0 cells. This data supports the idea that yeast mtDNA replication is initiated by a DSB and bKu inhibits mtDNA replication by binding to a DSB at ori5, preventing mtDNA segregation to daughter cells. Interestingly, we find that mitochondrial-targeted bKu does not decrease mtDNA content in human MCF7 cells. This finding is in agreement with the fact that human mtDNA replication, typically, is not initiated by a DSB. Therefore, this study provides evidence that DSB-mediated replication is the predominant form of mtDNA replication in ρ+ yeast cells. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Mechanism of homologous recombination and implications for aging-related deletions in mitochondrial DNA.

PubMed

Chen, Xin Jie

2013-09-01

Homologous recombination is a universal process, conserved from bacteriophage to human, which is important for the repair of double-strand DNA breaks. Recombination in mitochondrial DNA (mtDNA) was documented more than 4 decades ago, but the underlying molecular mechanism has remained elusive. Recent studies have revealed the presence of a Rad52-type recombination system of bacteriophage origin in mitochondria, which operates by a single-strand annealing mechanism independent of the canonical RecA/Rad51-type recombinases. Increasing evidence supports the notion that, like in bacteriophages, mtDNA inheritance is a coordinated interplay between recombination, repair, and replication. These findings could have profound implications for understanding the mechanism of mtDNA inheritance and the generation of mtDNA deletions in aging cells.

Mechanism of Homologous Recombination and Implications for Aging-Related Deletions in Mitochondrial DNA

PubMed Central

2013-01-01

SUMMARY Homologous recombination is a universal process, conserved from bacteriophage to human, which is important for the repair of double-strand DNA breaks. Recombination in mitochondrial DNA (mtDNA) was documented more than 4 decades ago, but the underlying molecular mechanism has remained elusive. Recent studies have revealed the presence of a Rad52-type recombination system of bacteriophage origin in mitochondria, which operates by a single-strand annealing mechanism independent of the canonical RecA/Rad51-type recombinases. Increasing evidence supports the notion that, like in bacteriophages, mtDNA inheritance is a coordinated interplay between recombination, repair, and replication. These findings could have profound implications for understanding the mechanism of mtDNA inheritance and the generation of mtDNA deletions in aging cells. PMID:24006472

Contrasting population structure from nuclear intron sequences and mtDNA of humpback whales.

PubMed

Palumbi, S R; Baker, C S

1994-05-01

Powerful analyses of population structure require information from multiple genetic loci. To help develop a molecular toolbox for obtaining this information, we have designed universal oligonucleotide primers that span conserved intron-exon junctions in a wide variety of animal phyla. We test the utility of exon-primed, intron-crossing amplifications by analyzing the variability of actin intron sequences from humpback, blue, and bowhead whales and comparing the results with mitochondrial DNA (mtDNA) haplotype data. Humpback actin introns fall into two major clades that exist in different frequencies in different oceanic populations. It is surprising that Hawaii and California populations, which are very distinct in mtDNAs, are similar in actin intron alleles. This discrepancy between mtDNA and nuclear DNA results may be due either to differences in genetic drift in mitochondrial and nuclear genes or to preferential movement of males, which do not transmit mtDNA to offspring, between separate breeding grounds. Opposing mtDNA and nuclear DNA results can help clarify otherwise hidden patterns of structure in natural populations.

Digital PCR Quantitation of Muscle Mitochondrial DNA: Age, Fiber Type, and Mutation-Induced Changes.

PubMed

Herbst, Allen; Widjaja, Kevin; Nguy, Beatrice; Lushaj, Entela B; Moore, Timothy M; Hevener, Andrea L; McKenzie, Debbie; Aiken, Judd M; Wanagat, Jonathan

2017-10-01

Definitive quantitation of mitochondrial DNA (mtDNA) and mtDNA deletion mutation abundances would help clarify the role of mtDNA instability in aging. To more accurately quantify mtDNA, we applied the emerging technique of digital polymerase chain reaction to individual muscle fibers and muscle homogenates from aged rodents. Individual fiber mtDNA content correlated with fiber type and decreased with age. We adapted a digital polymerase chain reaction deletion assay that was accurate in mixing experiments to a mutation frequency of 0.03% and quantitated an age-induced increase in deletion frequency from rat muscle homogenates. Importantly, the deletion frequency measured in muscle homogenates strongly correlated with electron transport chain-deficient fiber abundance determined by histochemical analyses. These data clarify the temporal accumulation of mtDNA deletions that lead to electron chain-deficient fibers, a process culminating in muscle fiber loss. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Comprehensive study of mtDNA among Southwest Asian dogs contradicts independent domestication of wolf, but implies dog–wolf hybridization

PubMed Central

Ardalan, Arman; Kluetsch, Cornelya F C; Zhang, Ai-bing; Erdogan, Metin; Uhlén, Mathias; Houshmand, Massoud; Tepeli, Cafer; Ashtiani, Seyed Reza Miraei; Savolainen, Peter

2011-01-01

Studies of mitochondrial DNA (mtDNA) diversity indicate explicitly that dogs were domesticated, probably exclusively, in southern East Asia. However, Southwest Asia (SwAsia) has had poor representation and geographical coverage in these studies. Other studies based on archaeological and genome-wide SNP data have suggested an origin of dogs in SwAsia. Hence, it has been suspected that mtDNA evidence for this scenario may have remained undetected. In the first comprehensive investigation of genetic diversity among SwAsian dogs, we analyzed 582 bp of mtDNA for 345 indigenous dogs from across SwAsia, and compared with 1556 dogs across the Old World. We show that 97.4% of SwAsian dogs carry haplotypes belonging to a universal mtDNA gene pool, but that only a subset of this pool, five of the 10 principal haplogroups, is represented in SwAsia. A high frequency of haplogroup B, potentially signifying a local origin, was not paralleled with the high genetic diversity expected for a center of origin. Meanwhile, 2.6% of the SwAsian dogs carried the rare non-universal haplogroup d2. Thus, mtDNA data give no indication that dogs originated in SwAsia through independent domestication of wolf, but dog–wolf hybridization may have formed the local haplogroup d2 within this region. Southern East Asia remains the only region with virtually full extent of genetic variation, strongly indicating it to be the primary and probably sole center of wolf domestication. An origin of dogs in southern East Asia may have been overlooked by other studies due to a substantial lack of samples from this region. PMID:22393507

Alternative Programs and the Reform of Teacher Education.

ERIC Educational Resources Information Center

Wisniewski, Richard

1986-01-01

Characteristics of professionally sound alternative preparation programs are discussed in terms of admissions, core courses, faculty and student time, simulation activities, and academic preparation. The Lyndhurst Fellowship Program at the University of Tennessee-Knoxville and Memphis State University is described. (MT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dobler, Jeremy; Zaccheo, T. Scott; Blume, Nathan

This report describes the development and testing of a novel system, the Greenhouse gas Laser Imaging Tomography Experiment (GreenLITE), for Monitoring, Reporting and Verification (MRV) of CO 2 at Geological Carbon Storage (GCS) sites. The system consists of a pair of laser based transceivers, a number of retroreflectors, and a set of cloud based data processing, storage and dissemination tools, which enable 2-D mapping of the CO 2 in near real time. A system was built, tested locally in New Haven, Indiana, and then deployed to the Zero Emissions Research and Technology (ZERT) facility in Bozeman, MT. Testing at ZERTmore » demonstrated the ability of the GreenLITE system to identify and map small underground leaks, in the presence of other biological sources and with widely varying background concentrations. The system was then ruggedized and tested at the Harris test site in New Haven, IN, during winter time while exposed to temperatures as low as -15 °CºC. Additional testing was conducted using simulated concentration enhancements to validate the 2-D retrieval accuracy. This test resulted in a high confidence in the reconstruction ability to identify sources to tens of meters resolution in this configuration. Finally, the system was deployed for a period of approximately 6 months to an active industrial site, Illinois Basin – Decatur Project (IBDP), where >1M metric tons of CO 2 had been injected into an underground sandstone basin. The main objective of this final deployment was to demonstrate autonomous operation over a wide range of environmental conditions with very little human interaction, and to demonstrate the feasibility of the system for long term deployment in a GCS environment.« less

Plasmid Detection in Legionella pneumophila and Legionella-like Organisms.

DTIC Science & Technology

1980-04-30

in view of the narrow spectrum of antibiotics effective in the treatment of legionellosis and Legionella-like diseases , the acquisition of drug...pneumonia. Ann. Intern. Med. 91:831-834. 15. McDade, J. E., D. J. Brenner, and F. M. Bozeman. 1979. Legionnaires ’ disease bacterium isolated in 1947...AD-ASM 700 ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FR--ETC F/6 6/5 PLASNIC DETECTION IN LEGIONELLA PNEUNOPHILA ND LESIONELLA-LIKE--ETe(U

Shielding analysis of the Microtron MT-25 bunker using the MCNP-4C code and NCRP Report 51.

PubMed

Casanova, A O; López, N; Gelen, A; Guevara, M V Manso; Díaz, O; Cimino, L; D'Alessandro, K; Melo, J C

2004-01-01

A cyclic electron accelerator Microtron MT-25 will be installed in Havana, Cuba. Electrons, neutrons and gamma radiation up to 25 MeV can be produced in the MT-25. A detailed shielding analysis for the bunker is carried out using two ways: the NCRP-51 Report and the Monte Carlo Method (MCNP-4C Code). The walls and ceiling thicknesses are estimated with dose constraints of 0.5 and 20 mSv y(-1), respectively, and an area occupancy factor of 1/16. Both results are compared and a preliminary bunker design is shown. Copyright 2004 Oxford University Press

Distribution of the coenzyme M pathway of epoxide metabolism among ethene- and vinyl chloride-degrading Mycobacterium strains.

PubMed

Coleman, Nicholas V; Spain, Jim C

2003-10-01

An epoxyalkane:coenzyme M (CoM) transferase (EaCoMT) enzyme was recently found to be active in the aerobic vinyl chloride (VC) and ethene assimilation pathways of Mycobacterium strain JS60. In the present study, EaCoMT activity and genes were investigated in 10 different mycobacteria isolated on VC or ethene from diverse environmental samples. In all cases, epoxyethane metabolism in cell extracts was dependent on CoM, with average specific activities of EaCoMT between 380 and 2,910 nmol/min/mg of protein. PCR with primers based on conserved regions of EaCoMT genes from Mycobacterium strain JS60 and the propene oxidizers Xanthobacter strain Py2 and Rhodococcus strain B-276 yielded fragments (834 bp) of EaCoMT genes from all of the VC- and ethene-assimilating isolates. The Mycobacterium EaCoMT genes form a distinct cluster and are more closely related to the EaCoMT of Rhodococcus strain B-276 than that of Xanthobacter strain Py2. The incongruence of the EaCoMT and 16S rRNA gene trees and the fact that isolates from geographically distant locations possessed almost identical EaCoMT genes suggest that lateral transfer of EaCoMT among the Mycobacterium strains has occurred. Pulsed-field gel electrophoresis revealed large linear plasmids (110 to 330 kb) in all of the VC-degrading strains. In Southern blotting experiments, the strain JS60 EaCoMT gene hybridized to many of the plasmids. The CoM-mediated pathway of epoxide metabolism appears to be universal in alkene-assimilating mycobacteria, possibly because of plasmid-mediated lateral gene transfer.

mtDNA-Server: next-generation sequencing data analysis of human mitochondrial DNA in the cloud.

PubMed

Weissensteiner, Hansi; Forer, Lukas; Fuchsberger, Christian; Schöpf, Bernd; Kloss-Brandstätter, Anita; Specht, Günther; Kronenberg, Florian; Schönherr, Sebastian

2016-07-08

Next generation sequencing (NGS) allows investigating mitochondrial DNA (mtDNA) characteristics such as heteroplasmy (i.e. intra-individual sequence variation) to a higher level of detail. While several pipelines for analyzing heteroplasmies exist, issues in usability, accuracy of results and interpreting final data limit their usage. Here we present mtDNA-Server, a scalable web server for the analysis of mtDNA studies of any size with a special focus on usability as well as reliable identification and quantification of heteroplasmic variants. The mtDNA-Server workflow includes parallel read alignment, heteroplasmy detection, artefact or contamination identification, variant annotation as well as several quality control metrics, often neglected in current mtDNA NGS studies. All computational steps are parallelized with Hadoop MapReduce and executed graphically with Cloudgene. We validated the underlying heteroplasmy and contamination detection model by generating four artificial sample mix-ups on two different NGS devices. Our evaluation data shows that mtDNA-Server detects heteroplasmies and artificial recombinations down to the 1% level with perfect specificity and outperforms existing approaches regarding sensitivity. mtDNA-Server is currently able to analyze the 1000G Phase 3 data (n = 2,504) in less than 5 h and is freely accessible at https://mtdna-server.uibk.ac.at. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cosmic Ray research in Armenia

NASA Astrophysics Data System (ADS)

Chilingarian, A.; Mirzoyan, R.; Zazyan, M.

2009-11-01

Cosmic Ray research on Mt. Aragats began in 1934 with the measurements of East-West anisotropy by the group from Leningrad Physics-Technical Institute and Norair Kocharian from Yerevan State University. Stimulated by the results of their experiments in 1942 Artem and Abraham Alikhanyan brothers organized a scientific expedition to Aragats. Since that time physicists were studying Cosmic Ray fluxes on Mt. Aragats with various particle detectors: mass spectrometers, calorimeters, transition radiation detectors, and huge particle detector arrays detecting protons and nuclei accelerated in most violent explosions in Galaxy. Latest activities at Mt. Aragats include Space Weather research with networks of particle detectors located in Armenia and abroad, and detectors of Space Education center in Yerevan.

Report on National Collegiate Alcohol Awareness Week, Fall 1988.

ERIC Educational Resources Information Center

Rapaport, Ross J.

This document presents a report of the education and prevention activities undertaken at Central Michigan University in Mt. Pleasant, Michiagn, during the fall semester of 1988, in recognition of National Collegiate Alcohol Awareness Week (NCAAW). The document begins with a brief review of the university's campus-wide programs, goals, and…

Drug Testing in a University Athletic Program: Protocol and Implementation.

ERIC Educational Resources Information Center

Rovere, George D.; And Others

1986-01-01

An athletic drug education, counseling, and screening program at Wake Forest University is described. Decisions regarding which athletes to test, which drugs to test for and how to test for them, how to collect urine samples, and measures taken for a positive result are discussed. (MT)

A Computer Aided Statistical Covariance Program for Missile System Analysis

DTIC Science & Technology

1974-04-01

the example (rl) on the IBM 360/65 at Oklahoma State University. REFERENCES Euler 40 (r=l) (1) James R. R^wland and Willard M. Holmes,"Stochastic...B21P 1PIt RK 1, PYAK ItP YBK1 PYIKI, 144 2W01 DQ1 ,PYLI MtRLI MtGBI AStQBIAS , RBIAS PB, QBt RBtUEvVEWEt 145 3THETAt PHI tPS I t X tY ,Z SD. XTCGt YTC3

Mitochondrial DNA mutations and cognition: a case-series report.

PubMed

Inczedy-Farkas, Gabriella; Trampush, Joey W; Perczel Forintos, Dora; Beech, Danielle; Andrejkovics, Monika; Varga, Zsofia; Remenyi, Viktoria; Bereznai, Benjamin; Gal, Aniko; Molnar, Maria Judit

2014-06-01

Mutations in the mitochondrial genome can impair normal metabolic function in the central nervous system (CNS) where cellular energy demand is high. Primary mitochondrial DNA (mtDNA) mutations have been linked to several mitochondrial disorders that have comorbid psychiatric, neurologic, and cognitive sequelae. Here, we present a series of cases with primary mtDNA mutations who were genotyped and evaluated across a common neuropsychological battery. Nineteen patients with mtDNA mutations were genotyped and clinically and cognitively evaluated. Pronounced deficits in nonverbal/visuoperceptual reasoning, verbal recall, semantic word generativity, and processing speed were evident and consistent with a "mitochondrial dementia" that has been posited. However, variation in cognitive performance was noteworthy, suggesting that the phenotypic landscape of cognition linked to primary mtDNA mutations is heterogeneous. Our patients with mtDNA mutations evidenced cognitive deficits quite similar to those commonly seen in Alzheimer's disease and could have clinical relevance to the evaluation of dementia. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The ecological significance of biofilm formation by plant-associated bacteria.

PubMed

Morris, Cindy E; Monier, Jean-Michel

2003-01-01

Bacteria associated with plants have been observed frequently to form assemblages referred to as aggregates, microcolonies, symplasmata, or biofilms on leaves and on root surfaces and within intercellular spaces of plant tissues. In a wide range of habitats, biofilms are purported to be microniches of conditions markedly different from those of the ambient environment and drive microbial cells to effect functions not possible alone or outside of biofilms. This review constructs a portrait of how biofilms associated with leaves, roots and within intercellular spaces influence the ecology of the bacteria they harbor and the relationship of bacteria with plants. We also consider how biofilms may enhance airborne dissemination, ubiquity and diversification of plant-associated bacteria and may influence strategies for biological control of plant disease and for assuring food safety. Trapped by a nexus, coordinates uncertain Ever expanding or contracting Cannibalistic and scavenging sorties Excavations through signs of past alliances Consensus signals sound revelry Then time warped by viscosity Genomes showing codependence A virtual microbial beach party With no curfew and no time-out A few estranged cells seeking exit options, Looking for another menagerie. David Sands, Montana State University, Bozeman, February 2003

Multispectral imaging of plant stress for detection of CO2 leaking from underground

NASA Astrophysics Data System (ADS)

Rouse, J.; Shaw, J. A.; Repasky, K. S.; Lawrence, R. L.

2008-12-01

Multispectral imaging of plant stress is a potentially useful method of detecting CO2 leaking from underground. During the summers of 2007 and 2008, we deployed a multispectral imager for vegetation sensing as part of an underground CO2 release experiment conducted at the Zero Emission Research and Technology (ZERT) field site near the Montana State University campus in Bozeman, Montana. The imager was mounted on a low tower and observed the vegetation in a region near an underground pipe during a multi-week CO2 release. The imager was calibrated to measure absolute reflectance, from which vegetation indices were calculated as a measure of vegetation health. The temporal evolution of these indices over the course of the experiment show that the vegetation nearest the pipe exhibited more stress than the vegetation located further from the pipe. The imager observed notably increased stress in vegetation at locations exhibiting particularly high flux of CO2 from the ground into the atmosphere. These data from the 2007 and 2008 experiments will be used to demonstrate the utility of a tower-mounted multispectral imaging system for detecting CO2 leakage from below ground with the ability to operate continuously during clear and cloudy conditions.

Molecular regulation of sex change induced by methyltestosterone -feeding and methyltestosterone -feeding withdrawal in the protogynous orange-spotted grouper.

PubMed

Wang, Qing; Liu, Yun; Peng, Cheng; Wang, Xiang; Xiao, Ling; Wang, Dengdong; Chen, Jiaxing; Zhang, Haifa; Zhao, Huihong; Li, Shuisheng; Zhang, Yong; Lin, Haoran

2017-08-01

The sex identity of fish can be easily manipulated by exogenous hormones. Treatment with 17-methyltestosterone (MT) has been widely used to induce a male fate, but the molecular and cellular processes underlying sex changes induced by MT treatments and the withdrawal of MT are not well studied. In this study, we systematically investigated gonadal histology, gene expression profiles, sex steroid hormone levels, and cellular changes during sex changes induced by MT-feeding and MT-feeding withdrawal in the protogynous orange-spotted grouper, Epinephelus coioides. Based on gonadal histology, we demonstrated that MT-feeding-induced sex reversal can be divided into early and late phases: in the early phase, male and female germ cells coexist, and MT-feeding withdrawal leads to a female fate; in the late phase, only male germ cells are observed, and MT-feeding withdrawal does not reverse the process, leading to a male fate. In both the early and late phases, cytochrome P450 family19 subfamily A member 1 (cyp19a1a) gene expression increased in response to MT-feeding withdrawal. Finally, by tracing doublesex- and Mab-3-related transcription factor 1 (dmrt1)-expressing cells, we found that gonia-like cells in the germinal epithelium might be the major germ cell sources for developing testes during sex reversal. Collectively, our findings provide insights into the molecular and cellular mechanisms underlying sex changes induced by exogenous hormones. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Missing genes, multiple ORFs, and C-to-U type RNA editing in Acrasis kona (Heterolobosea, Excavata) mitochondrial DNA.

PubMed

Fu, Cheng-Jie; Sheikh, Sanea; Miao, Wei; Andersson, Siv G E; Baldauf, Sandra L

2014-08-21

Discoba (Excavata) is an ancient group of eukaryotes with great morphological and ecological diversity. Unlike the other major divisions of Discoba (Jakobida and Euglenozoa), little is known about the mitochondrial DNAs (mtDNAs) of Heterolobosea. We have assembled a complete mtDNA genome from the aggregating heterolobosean amoeba, Acrasis kona, which consists of a single circular highly AT-rich (83.3%) molecule of 51.5 kb. Unexpectedly, A. kona mtDNA is missing roughly 40% of the protein-coding genes and nearly half of the transfer RNAs found in the only other sequenced heterolobosean mtDNAs, those of Naegleria spp. Instead, over a quarter of A. kona mtDNA consists of novel open reading frames. Eleven of the 16 protein-coding genes missing from A. kona mtDNA were identified in its nuclear DNA and polyA RNA, and phylogenetic analyses indicate that at least 10 of these 11 putative nuclear-encoded mitochondrial (NcMt) proteins arose by direct transfer from the mitochondrion. Acrasis kona mtDNA also employs C-to-U type RNA editing, and 12 homologs of DYW-type pentatricopeptide repeat (PPR) proteins implicated in plant organellar RNA editing are found in A. kona nuclear DNA. A mapping of mitochondrial gene content onto a consensus phylogeny reveals a sporadic pattern of relative stasis and rampant gene loss in Discoba. Rampant loss occurred independently in the unique common lineage leading to Heterolobosea + Tsukubamonadida and later in the unique lineage leading to Acrasis. Meanwhile, mtDNA gene content appears to be remarkably stable in the Acrasis sister lineage leading to Naegleria and in their distant relatives Jakobida. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

MSeqDR mvTool: A mitochondrial DNA Web and API resource for comprehensive variant annotation, universal nomenclature collation, and reference genome conversion.

PubMed

Shen, Lishuang; Attimonelli, Marcella; Bai, Renkui; Lott, Marie T; Wallace, Douglas C; Falk, Marni J; Gai, Xiaowu

2018-06-01

Accurate mitochondrial DNA (mtDNA) variant annotation is essential for the clinical diagnosis of diverse human diseases. Substantial challenges to this process include the inconsistency in mtDNA nomenclatures, the existence of multiple reference genomes, and a lack of reference population frequency data. Clinicians need a simple bioinformatics tool that is user-friendly, and bioinformaticians need a powerful informatics resource for programmatic usage. Here, we report the development and functionality of the MSeqDR mtDNA Variant Tool set (mvTool), a one-stop mtDNA variant annotation and analysis Web service. mvTool is built upon the MSeqDR infrastructure (https://mseqdr.org), with contributions of expert curated data from MITOMAP (https://www.mitomap.org) and HmtDB (https://www.hmtdb.uniba.it/hmdb). mvTool supports all mtDNA nomenclatures, converts variants to standard rCRS- and HGVS-based nomenclatures, and annotates novel mtDNA variants. Besides generic annotations from dbNSFP and Variant Effect Predictor (VEP), mvTool provides allele frequencies in more than 47,000 germline mitogenomes, and disease and pathogenicity classifications from MSeqDR, Mitomap, HmtDB and ClinVar (Landrum et al., 2013). mvTools also provides mtDNA somatic variants annotations. "mvTool API" is implemented for programmatic access using inputs in VCF, HGVS, or classical mtDNA variant nomenclatures. The results are reported as hyperlinked html tables, JSON, Excel, and VCF formats. MSeqDR mvTool is freely accessible at https://mseqdr.org/mvtool.php. © 2018 Wiley Periodicals, Inc.

Mitochondrial DNA sequence characteristics modulate the size of the genetic bottleneck.

PubMed

Wilson, Ian J; Carling, Phillipa J; Alston, Charlotte L; Floros, Vasileios I; Pyle, Angela; Hudson, Gavin; Sallevelt, Suzanne C E H; Lamperti, Costanza; Carelli, Valerio; Bindoff, Laurence A; Samuels, David C; Wonnapinij, Passorn; Zeviani, Massimo; Taylor, Robert W; Smeets, Hubert J M; Horvath, Rita; Chinnery, Patrick F

2016-03-01

With a combined carrier frequency of 1:200, heteroplasmic mitochondrial DNA (mtDNA) mutations cause human disease in ∼1:5000 of the population. Rapid shifts in the level of heteroplasmy seen within a single generation contribute to the wide range in the severity of clinical phenotypes seen in families transmitting mtDNA disease, consistent with a genetic bottleneck during transmission. Although preliminary evidence from human pedigrees points towards a random drift process underlying the shifting heteroplasmy, some reports describe differences in segregation pattern between different mtDNA mutations. However, based on limited observations and with no direct comparisons, it is not clear whether these observations simply reflect pedigree ascertainment and publication bias. To address this issue, we studied 577 mother-child pairs transmitting the m.11778G>A, m.3460G>A, m.8344A>G, m.8993T>G/C and m.3243A>G mtDNA mutations. Our analysis controlled for inter-assay differences, inter-laboratory variation and ascertainment bias. We found no evidence of selection during transmission but show that different mtDNA mutations segregate at different rates in human pedigrees. m.8993T>G/C segregated significantly faster than m.11778G>A, m.8344A>G and m.3243A>G, consistent with a tighter mtDNA genetic bottleneck in m.8993T>G/C pedigrees. Our observations support the existence of different genetic bottlenecks primarily determined by the underlying mtDNA mutation, explaining the different inheritance patterns observed in human pedigrees transmitting pathogenic mtDNA mutations. © The Author 2016. Published by Oxford University Press.

Effect of manual therapy versus proprioceptive neuromuscular facilitation in dynamic balance, mobility and flexibility in field hockey players. A randomized controlled trial.

PubMed

Espí-López, Gemma V; López-Martínez, Susana; Inglés, Marta; Serra-Añó, Pilar; Aguilar-Rodríguez, Marta

2018-04-22

To compare the effectiveness of a specific Manual Therapy (MT) protocol applied to field hockey players (FHP), versus a Proprioceptive Neuromuscular Facilitation (PNF) protocol, in the improvement of dynamic balance, active range of movement and lumbar flexibility one-week and four-weeks after the treatment. Randomized controlled trial. Participants were assigned to 2 groups: MT and PNF. 30 min' sessions were performed once a week for three weeks. Three evaluations were performed: basal, one-week and four-weeks post-treatment. University of Valencia (Spain). 22 in MT group and 20 in PNF group. Dynamic Balance, measured with Star Excursion Balance Test; Active Range of Motion (ROM), using a manual goniometer and Lumbar Flexibility, assessed with Fingertip-to-floor test. Both groups significantly improved in lateral and medial dynamic balance one-week post-treatment (p < 0.05); but the improvement in the MT group lasted until the fourth-week after treatment in both reaches (lateral and medial) (p < 0.05). MT group also obtained significant improvements in dorsal flexion of the ankle in the fourth-week post-treatment (p < 0.05) and in lumbar flexibility one-week post-treatment (p < 0.05). MT and PNF improve dynamic balance one-week post-treatment; however, the improvement obtained through MT is maintained four-weeks later. Only MT improves dorsal flexion of the ankle four-weeks post-treatment and lumbar flexibility one-week post-treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of tributylborane-activated adhesive and two silane agents on bonding computer-aided design and manufacturing (CAD/CAM) resin composite.

PubMed

Shinohara, Ayano; Taira, Yohsuke; Sawase, Takashi

2017-10-01

The present study was conducted to evaluate the effects of an experimental adhesive agent [methyl methacrylate-tributylborane liquid (MT)] and two adhesive agents containing silane on the bonding between a resin composite block of a computer-aided design and manufacturing (CAD/CAM) system and a light-curing resin composite veneering material. The surfaces of CAD/CAM resin composite specimens were ground with silicon-carbide paper, treated with phosphoric acid, and then primed with either one of the two silane agents [Scotchbond Universal Adhesive (SC) and GC Ceramic Primer II (GC)], no adhesive control (Cont), or one of three combinations (MT/SC, MT/GC, and MT/Cont). A light-curing resin composite was veneered on the primed CAD/CAM resin composite surface. The veneered specimens were subjected to thermocycling between 4 and 60 °C for 10,000 cycles, and the shear bond strengths were determined. All data were analyzed using analysis of variance and a post hoc Tukey-Kramer HSD test (α = 0.05, n = 8). MT/SC (38.7 MPa) exhibited the highest mean bond strengths, followed by MT/GC (30.4 MPa), SC (27.9 MPa), and MT/Cont (25.7 MPa), while Cont (12.9 MPa) and GC (12.3 MPa) resulted in the lowest bond strengths. The use of MT in conjunction with a silane agent significantly improved the bond strength. Surface treatment with appropriate adhesive agents was confirmed as a prerequisite for veneering CAD/CAM resin composite restorations.

Report of National Collegiate Alcohol Awareness Week Activities Fall 1987.

ERIC Educational Resources Information Center

Owens, Ann English; And Others

This document presents a report of the education and prevention activities recognizing National Collegiate Alcohol Awareness (NCAA) Week undertaken at Central Michigan University in Mt. Pleasant, Michigan during October and early November, 1987. It begins with a brief review of the university's campus-wide programs, goals, and activities to reduce…

Magnetotelluric Investigations of the Yellowstone Caldera: Understanding the Emplacement of Crustal Magma Bodies

NASA Astrophysics Data System (ADS)

Gurrola, R. M.; Neal, B. A.; Bennington, N. L.; Cronin, R.; Fry, B.; Hart, L.; Imamura, N.; Kelbert, A.; Bowles-martinez, E.; Miller, D. J.; Scholz, K. J.; Schultz, A.

2017-12-01

Wideband magnetotellurics (MT) presents an ideal method for imaging conductive shallow magma bodies associated with contemporary Yellowstone-Snake River Plain (YSRP) magmatism. Particularly, how do these magma bodies accumulate in the mid to upper crust underlying the Yellowstone Caldera, and furthermore, what role do hydrothermal fluids play in their ascent? During the summer 2017 field season, two field teams from Oregon State University and the University of Wisconsin-Madison installed forty-four wideband MT stations within and around the caldera, and using data slated for joint 3-D inversion with existing seismic data, two 2-D vertical conductivity sections of the crust and upper mantle were constructed. These models, in turn, provide preliminary insight into the emplacement of crustal magma bodies and hydrothermal processes in the YSRP region.

MitoAge: a database for comparative analysis of mitochondrial DNA, with a special focus on animal longevity.

PubMed

Toren, Dmitri; Barzilay, Thomer; Tacutu, Robi; Lehmann, Gilad; Muradian, Khachik K; Fraifeld, Vadim E

2016-01-04

Mitochondria are the only organelles in the animal cells that have their own genome. Due to a key role in energy production, generation of damaging factors (ROS, heat), and apoptosis, mitochondria and mtDNA in particular have long been considered one of the major players in the mechanisms of aging, longevity and age-related diseases. The rapidly increasing number of species with fully sequenced mtDNA, together with accumulated data on longevity records, provides a new fascinating basis for comparative analysis of the links between mtDNA features and animal longevity. To facilitate such analyses and to support the scientific community in carrying these out, we developed the MitoAge database containing calculated mtDNA compositional features of the entire mitochondrial genome, mtDNA coding (tRNA, rRNA, protein-coding genes) and non-coding (D-loop) regions, and codon usage/amino acids frequency for each protein-coding gene. MitoAge includes 922 species with fully sequenced mtDNA and maximum lifespan records. The database is available through the MitoAge website (www.mitoage.org or www.mitoage.info), which provides the necessary tools for searching, browsing, comparing and downloading the data sets of interest for selected taxonomic groups across the Kingdom Animalia. The MitoAge website assists in statistical analysis of different features of the mtDNA and their correlative links to longevity. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Hearing on the Reauthorization of the National Endowments for the Arts and Humanities and the Institute of Museum Services. Hearing before the Subcommitee on Postsecondary Education of the Committee on Education and Labor. House of Representatives, One Hundred First Congress, First Session (Bozeman, Montana, April 1, 1989).

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Education and Labor.

The hearing was opened by Representative Pat Williams of Montana, who explained that the Subcommittee on Postsecondary Education of which he is chairman, has jurisdiction over the National Endowments for Arts and Humanities and the Institute of Museum Services (IMS), and that programs in these agencies account for the largest portion of federal…

Indian Wars: Failings of the United States Army to Achieve Decisive Victory During the NEZ Perce War of 1877

DTIC Science & Technology

2005-06-17

Walla Ft. Walsh Ft. Missoula IDAHO TERRITORY OREGON Bozeman Butte Deer Lodge Helena Virginia City Cooke City Salmon Mis sour i R. Lewiston Sn ak e R...the US Government’s treaty demands aimed at removing their tribe from the Wallowa Valley to a small reservation in Idaho . This band of Nez Perce...who ruled the West; in the areas now know as Oregon, Idaho , Montana, and Wyoming.9 After putting up many valiant fights, and inflicting a great

Compact, Robust Chips Integrate Optical Functions

NASA Technical Reports Server (NTRS)

2010-01-01

Located in Bozeman, Montana, AdvR Inc. has been an active partner in NASA's Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Langley Research Center engineers partnered with AdvR through the SBIR program to develop new, compact, lightweight electro-optic components for remote sensing systems. While the primary customer for this technology will be NASA, AdvR foresees additional uses for its NASA-derived circuit chip in the fields of academic and industrial research anywhere that compact, low-cost, stabilized single-frequency lasers are needed.

An association analysis between mitochondrial DNA content, G10398A polymorphism, HPV infection, and the prognosis of cervical cancer in the Chinese Han population.

PubMed

Feng, Dali; Xu, Hui; Li, Xin; Wei, Yuehua; Jiang, Huangang; Xu, Hong; Luo, Aihua; Zhou, Fuxiang

2016-04-01

The aim was to analyze quantitative (mitochondrial DNA (mtDNA) content) and qualitative (G10398A polymorphism) mtDNA alterations as well as human papillomavirus (HPV) infection in cervical cancer prognosis. One hundred and twenty-two cases of formalin-fixed paraffin-embedded cervical carcinoma specimens were collected from the Yichang Tumor Hospital and Zhongnan Hospital of Wuhan University in the recent 10 years together with medical records. A quantitative real-time PCR (RT-PCR) was used to determine the copy number of the mitochondrial DNA and HPV expression levels. G10398A polymorphism was determined by PCR-RFLP assay. The overall survival of patients with higher mtDNA content was significantly reduced compared with lower mtDNA content patients (P = 0.029). But there was no difference of prognosis between the mtDNA 10398 A allele and G allele. However, the Kaplan-Meier survival curve illustrated a significantly reduced overall survival in the patients with 10398A plus high mtDNA copy number compared with the other groups (P < 0.05). Although no association between HPV expression level and cervical cancer prognosis was observed, 10398A got increased mtDNA content compared with 10398G (P < 0.05) and 10398G displayed an increased HPV-positive rate compared with 10398A. Furthermore, HPV-18 and mtDNA content were positively related in the younger subgroup (≤45 years) (correlation coefficient = 0.456, P = 0.022). This study indicated that mtDNA content and HPV infection status are associated with cervical cancer prognosis. High mitochondrial DNA content plus 10398 A may be a marker of poor prognosis in cervical cancer. And mtDNA variation may potentially influence the predisposition to HPV infection and cervical carcinogenesis.

Pretraining Cortical Thickness Predicts Subsequent Perceptual Learning Rate in a Visual Search Task.

PubMed

Frank, Sebastian M; Reavis, Eric A; Greenlee, Mark W; Tse, Peter U

2016-03-01

We report that preexisting individual differences in the cortical thickness of brain areas involved in a perceptual learning task predict the subsequent perceptual learning rate. Participants trained in a motion-discrimination task involving visual search for a "V"-shaped target motion trajectory among inverted "V"-shaped distractor trajectories. Motion-sensitive area MT+ (V5) was functionally identified as critical to the task: after 3 weeks of training, activity increased in MT+ during task performance, as measured by functional magnetic resonance imaging. We computed the cortical thickness of MT+ from anatomical magnetic resonance imaging volumes collected before training started, and found that it significantly predicted subsequent perceptual learning rates in the visual search task. Participants with thicker neocortex in MT+ before training learned faster than those with thinner neocortex in that area. A similar association between cortical thickness and training success was also found in posterior parietal cortex (PPC). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Unsupervised quality estimation model for English to German translation and its application in extensive supervised evaluation.

PubMed

Han, Aaron L-F; Wong, Derek F; Chao, Lidia S; He, Liangye; Lu, Yi

2014-01-01

With the rapid development of machine translation (MT), the MT evaluation becomes very important to timely tell us whether the MT system makes any progress. The conventional MT evaluation methods tend to calculate the similarity between hypothesis translations offered by automatic translation systems and reference translations offered by professional translators. There are several weaknesses in existing evaluation metrics. Firstly, the designed incomprehensive factors result in language-bias problem, which means they perform well on some special language pairs but weak on other language pairs. Secondly, they tend to use no linguistic features or too many linguistic features, of which no usage of linguistic feature draws a lot of criticism from the linguists and too many linguistic features make the model weak in repeatability. Thirdly, the employed reference translations are very expensive and sometimes not available in the practice. In this paper, the authors propose an unsupervised MT evaluation metric using universal part-of-speech tagset without relying on reference translations. The authors also explore the performances of the designed metric on traditional supervised evaluation tasks. Both the supervised and unsupervised experiments show that the designed methods yield higher correlation scores with human judgments.

Spectral Signatures of Feedforward and Recurrent Circuitry in Monkey Area MT.

PubMed

Solomon, Selina S; Morley, John W; Solomon, Samuel G

2017-05-01

Recordings of local field potential (LFP) in the visual cortex can show rhythmic activity at gamma frequencies (30-100 Hz). While the gamma rhythms in the primary visual cortex have been well studied, the structural and functional characteristics of gamma rhythms in extrastriate visual cortex are less clear. Here, we studied the spatial distribution and functional specificity of gamma rhythms in extrastriate middle temporal (MT) area of visual cortex in marmoset monkeys. We found that moving gratings induced narrowband gamma rhythms across cortical layers that were coherent across much of area MT. Moving dot fields instead induced a broadband increase in LFP in middle and upper layers, with weaker narrowband gamma rhythms in deeper layers. The stimulus dependence of LFP response in middle and upper layers of area MT appears to reflect the presence (gratings) or absence (dot fields and other textures) of strongly oriented contours. Our results suggest that gamma rhythms in these layers are propagated from earlier visual cortex, while those in the deeper layers may emerge in area MT. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Survival, Growth and Reproduction of Non-Native Nile Tilapia II: Fundamental Niche Projections and Invasion Potential in the Northern Gulf of Mexico

DTIC Science & Technology

2012-07-27

Cambridge University Press. 47. Gritti ESB, Smith B, Sykes MT (2006) Vulnerability of Mediterranean Basin ecosystems to climate change and invasion by...2011) Monitoring diets and growth rates of native predatory fish stocked to suppress non-native tilapia. MS Thesis, Nicholls State University

Aristotle University Astronomical Station at Mt. Holomon

NASA Astrophysics Data System (ADS)

Avdellidou, C.; Ioannidis, P.; Kouroubatzakis, K.; Nitsos, A.; Vakoulis, J.; Seiradakis, J. H.

2012-01-01

The Aristotle University Astronomical Station was established seven years ago in order to fulfill the educational needs of its students. Astronomical observations are undertaken using three fully equipped small telescopes. Some interesting results are presented below, including the study of asteroids and flare stars, the detection of optical emission from supernovae remnants and follow up observations in extra solar planets.

[Publications of medical thesis defended in Lille school of medicine].

PubMed

Benotmane, Ilies; Glatz, Nicolas; Bihan, Solenn; Legrand, Fanny; Gosset, Didier; Boulanger, Eric

2012-07-01

The purpose of this study was to determine the future, in terms of scientific publication, of medical thesis (MT) defended in the Medical School of Lille 2 University (MSL2U) between January 1st, 2001 and December 31st, 2007. The collection of MT published as a corresponding scientific article was realized from PubMed(®). For every corresponding article, we determined the journal Impact Factor (IF), the language of publication and the rank of the student and his MT director in the author list. Analyses were also realized according to the group of speciality of the TM. In all, 11.3% of the 2150 MT defended in the MSL2U were followed up by a scientific publication. The average IF was 2.32 with a median at 1.75 and extreme values from 0 to 14.78. Seventy percent of the articles were published in English. The rank of the student was placed before his MT director (2.06 vs. 3.15). The MT defended by students in the field of medical specialities presented the highest rate of publication (25.1%). The general medicine was the second speciality the most productive in term of number of published articles (n=49) after medical specialities (n=103). The MT director and the PhD students must be more motivated to publish their results. The value of 11.3% could be considered as weak but, because of a huge lack of references, it is impossible to compare our results to those of other French medical schools. It remains important to reform the objectives and the modalities of the writing of a MT: should we not have to turn to thesis called "on article"? Copyright © 2012. Published by Elsevier Masson SAS.

Preliminary study of online machine translation use of nursing literature: quality evaluation and perceived usability

PubMed Central

2012-01-01

Background Japanese nurses are increasingly required to read published international research in clinical, educational, and research settings. Language barriers are a significant obstacle, and online machine translation (MT) is a tool that can be used to address this issue. We examined the quality of Google Translate® (English to Japanese and Korean to Japanese), which is a representative online MT, using a previously verified evaluation method. We also examined the perceived usability and current use of online MT among Japanese nurses. Findings Randomly selected nursing abstracts were translated and then evaluated for intelligibility and usability by 28 participants, including assistants and research associates from nursing universities throughout Japan. They answered a questionnaire about their online MT use. From simple comparison of mean scores between two language pairs, translation quality was significantly better, with respect to both intelligibility and usability, for Korean-Japanese than for English-Japanese. Most respondents perceived a language barrier. Online MT had been used by 61% of the respondents and was perceived as not useful enough. Conclusion Nursing articles translated from Korean into Japanese by an online MT system could be read at an acceptable level of comprehension, but the same could not be said for English-Japanese translations. Respondents with experience using online MT used it largely to grasp the overall meanings of the original text. Enrichment in technical terms appeared to be the key to better usability. Users will be better able to use MT outputs if they improve their foreign language proficiency as much as possible. Further research is being conducted with a larger sample size and detailed analysis. PMID:23151362

Patient education with or without manual therapy compared to a control group in patients with osteoarthritis of the hip. A proof-of-principle three-arm parallel group randomized clinical trial.

PubMed

Poulsen, E; Hartvigsen, J; Christensen, H W; Roos, E M; Vach, W; Overgaard, S

2013-10-01

To investigate the effectiveness of a patient education (PE) program with or without the added effect of manual therapy (MT) compared to a minimal control intervention (MCI). In a single-center university hospital setting, a total of 118 patients with clinical and radiographic unilateral hip osteoarthritis (OA) from primary care were randomized into one of three groups: PE, PE plus MT or MCI. The PE was taught by a physiotherapist involving five sessions. The MT was delivered by a chiropractor involving 12 sessions and the MCI included a home stretching program. Primary outcome was self-reported pain severity on an 11-box numeric rating scale (NRS) immediately following a 6-week intervention period. Patients were followed for 1 year. Primary analysis included 111 patients (94%). In the combined group (PE + MT), a clinically relevant reduction in pain severity compared to the MCI of 1.90 points (95% confidence interval (CI) 0.9-2.9) was achieved. Effect size (Cohen's d) for the PE + MT minus the MCI was 0.92 (95% CI 0.41-1.42). Number needed to treat for PE + MT was 3 (95% CI 2-7). No difference was found between the PE and MCI groups, with mean difference 0.0 (95% CI -1.0 to 1.0). At 12 months, not including patients receiving hip surgery the statistically significant difference favoring PE + MT was maintained. For primary care patients with OA of the hip, a combined intervention of MT and PE was more effective than a MCI. PE alone was not superior to the MCI. clinicaltrials.govNCT01039337. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Practical Examples of an Integrated Field Study Program at Mt. Fuji: Geosciences and the Arts

NASA Astrophysics Data System (ADS)

Ito, T.; Kamikuri, S. I.; Otsuji, H.; Kataguchi, N.; Maruyama, H.; Hashiura, H.

2017-12-01

Mt. Fuji is a symbol of existence for the Japanese and it also has been a religiously revered subject. In addition, as represented by the ukiyo-e of Hokusai and Hiroshige, it is a subject of paintings, as well as of various types of literary expression such as waka, haiku and novels. Historically, there was a time when Mt. Fuji was used as a symbol of the integration of the country; and it has long reflected the culture, life and thoughts of the Japanese. On another level, from the Earth scientific point of view, Mt. Fuji is one of the most active volcanoes in Japan. Teacher training colleges in Japan have created educational programs for all subjects taught at school. However, as there is no effective linkage among these subjects, students may have different opinions on them according to their curriculum. In this study, we adopted a multifaceted learning approach toward that most symbolic icon of our country. In FY2014 and FY2016, a course created by the College of Education at Ibaraki University, called "Fieldwork on Geology," was conducted at and around Mt. Fuji. In addition to conducting fieldwork from the viewpoint of earth science, it also had abundant artistic content. Academics in the fields of earth science, art and pedagogy worked closely together from the planning stage and participated in a field study with 25 university students. Specifically, we focused on how the experience of sketching a landscape affects field observations by broadening the viewpoint and deepening the understanding of students. To ascertain the bidirectional educational effects between earth sciences and art, students were asked: 1) to express an image of Mt. Fuji, and 2) to appreciate paintings of Mt. Fuji and express the information they garnered from the paintings, before and after the fieldwork. These two exercises are considered as providing insights into how the students' understanding had changed. In addition, reports and impressions submitted by the students were used as materials for putting the classes together. Results show that a large number of positive effects are obtained corresponding to the time and energy spent making sketches. It has also been suggested that the experience of onsite observations provides various novel and concrete viewpoints for the appreciation of paintings.

Stratigraphy and depositional environment of upper Cambrian Red Lion Formation, southwestern Montana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayden, L.L.; Bush, J.H.

1987-08-01

The Red Lion Formation was examined along a northwest-southeast transect from Missoula to Bozeman, Montana. Lateral equivalents are the Snowy Range Formation east of Bozeman and the upper Fishtrap Dolomite in northwest Montana. The basal Dry Creek Member (0-5 m) consists of shale interbedded with quartz siltstones and sandstones. The overlying Sage Member, up to 115 meters in thickness, is characterized by ribbon carbonate beds containing lime mudstone and quartzose calcisiltite couplets arranged in fining-upward sequences 1-5 cm thick. Couplets are interlayered in places with thin (1-5 cm) to medium bedded (6-70 cm) units of laminated and non-laminated calcareous siltstones,more » flat-pebble conglomerates, trilobite packstones, cryptalgal boundstones, bioturbated lime mudstones and shales. In places, the upper Sage contains columnar and domal algal features. The Red Lion Formation is considered to be one Grand Cycle with the Dry Creek representing a lower inner detrital half-cycle and the Sage an upper carbonate half-cycle. The Dry Creek formed as the result of a westward clastic pulse from the inner detrital belt across an intrashelf basin onto outer middle carbonate peritidal complexes of the underlying Pilgrim Formation. Lower Sage ribbon rocks were deposited in storm-crossed, below wave-base areas. During deposition of the upper Sage, shallowing formed discontinuous algal-peritidal complexes over much of western and central Montana. These complexes were less extensive than earlier Cambrian buildups owing to slower rates of basin subsidence and clastic input suppressing carbonate production.« less

Mt. Kilimanjaro expedition in earth science education

NASA Astrophysics Data System (ADS)

Sparrow, Elena; Yoshikawa, Kenji; Narita, Kenji; Brettenny, Mark; Yule, Sheila; O'Toole, Michael; Brettenny, Rogeline

2010-05-01

Mt. Kilimanjaro, Africa's highest mountain is 5,895 meters above sea level and is located 330 km south of the equator in Tanzania. In 1976 glaciers covered most of Mt. Kilimanjaro's summit; however in 2000, an estimated eighty percent of the ice cap has disappeared since the last thorough survey done in 1912. There is increased scientific interest in Mt. Kilimanjaro with the increase in global and African average temperatures. A team of college and pre-college school students from Tanzania, South Africa and Kenya, teachers from South Africa and the United States, and scientists from the University of Alaska Fairbanks in the United States and Akita University in Japan, climbed to the summit of Mt Kilimanjaro in October 2009. They were accompanied by guides, porters, two expedition guests, and a videographer. This expedition was part of the GLOBE Seasons and Biomes Earth System Science Project and the GLOBE Africa science education initiative, exploring and contributing to climate change studies. Students learned about earth science experientially by observing their physical and biological surroundings, making soil and air temperature measurements, participating in discussions, journaling their experience, and posing research questions. The international trekkers noted the change in the biomes as the altitude, temperature and conditions changed, from cultivated lands, to rain forest, heath zone, moorland, alpine desert, and summit. They also discovered permafrost, but not at the summit as expected. Rather, it was where the mountain was not covered by a glacier and thus more exposed to low extreme temperatures. This was the first report of permafrost on Mt. Kilimanjaro. Classrooms from all over the world participated in the expedition virtually. They followed the trek through the expedition website (http://www.xpeditiononline.com/) where pictures and journals were posted, and posed their own questions which were answered by the expedition and base camp team members. This was an opportunity for South African, Tanzanian and Kenyan students to work side by side with scientists, experience the wonder of summiting Africa's tallest mountain, and to learn hands-on earth science at a remote location. For students worldwide, it was an opportunity to share in the exciting earth science learning experience of going to the top of Africa without leaving their classrooms.

The Student Volunteer Movement for Foreign Missions and Its Contribution to Overall Missionary Service

ERIC Educational Resources Information Center

Harder, Ben

2011-01-01

The Student Volunteer Movement (SVM) for Foreign Missions was founded in 1886 at a Conference in the Mt. Hermon University, an organization designed to recruit college and university students in the United States and later of course through the Western world, for missionary service abroad. The primary leader of the SVM was A. T. Pierson, a major…

Lessons for Collaboration between Educational Agencies.

ERIC Educational Resources Information Center

Wu, P. C.

1986-01-01

School-university collaboration occurs only as a result of deliberate effort. Using trade between Nepal and Tibet as an illustration, elements of a successful collaboration are discussed, and examples are presented from Florida's Teacher Education Centers. (MT)

The Study of Children's Psychomotor Behavior. A Comprehensive Program.

ERIC Educational Resources Information Center

Gabbard, Carl P.

1985-01-01

The Child Movement Laboratory at Texas A&M University was created to provide a multifaceted approach to teacher preparation, research, and service regarding psychomotor behavior of children. This article discusses the program. (MT)

75 FR 28647 - Notice of Inventory Completion: University of Colorado Museum, Boulder, CO

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-21

... removed from Musselshell River, Meagher County, MT, possibly by Ralph Hubbard. One of the individuals appears to have sustained three gun-shot wounds. No known individuals were identified. No associated...

A review of terrorism and its reduction of the gender ratio at birth after seasonal adjustment.

PubMed

Grech, Victor; Zammit, Dorota

2017-12-01

Males are born in excess of females, a ratio expressed as M/T (males:total births). The ratio exhibits seasonal variation. Furthermore, acute stressful events may result in a transient dip in male births due to excess foetal losses, reducing M/T. This study was carried out in order to identify significant M/T dips after adjusting for seasonality. Live births by gender and month were sought for acute stressful events. After seasonal correction (where appropriate), M/T dips were sought. Live births. M/T dips. This paper studied 112,226,306 live births. The following events showed dips ≤5th percentile 3-5months after these acute episodes: the Brooklyn Bridge protests, Katrina Hurricane for all 4 states and for each individual state (Alabama, Florida, Louisiana, Mississippi), the Battle in Seattle, the London bombings, The Madrid bombings (for Madrid and for Spain), the Breivik shooting, the Oklahoma City bombing and the Sandy Hook Elementary School shooting. The Virginia Polytechnic Institute and State University shooting the Fukushima Daiichi nuclear disaster also showed dips albeit slightly later. Seasonal adjustments should be taken into consideration in order to avoid Type 1 or 2 error pitfalls. Copyright © 2017 Elsevier B.V. All rights reserved.

A Storm-by-Storm Analysis of Alpine and Regional Precipitation Dynamics at the Mount Hunter Ice Core Site, Denali National Park, Central Alaska Range

NASA Astrophysics Data System (ADS)

Saylor, P. L.; Osterberg, E. C.; Kreutz, K. J.; Wake, C. P.; Winski, D.

2014-12-01

In May-June 2013, an NSF-funded team from Dartmouth College and the Universities of Maine and New Hampshire collected two 1000-year ice cores to bedrock from the summit plateau of Mount Hunter in Denali National Park, Alaska (62.940291, -151.087616, 3912 m). The snow accumulation record from these ice cores will provide key insight into late Holocene precipitation variability in central Alaska, and compliment existing precipitation paleorecords from the Mt. Logan and Eclipse ice cores in coastal SE Alaska. However, correct interpretation of the Mt. Hunter accumulation record requires an understanding of the relationships between regional meteorological events and micrometeorological conditions at the Mt. Hunter ice core collection site. Here we analyze a three-month window of snow accumulation and meteorological conditions recorded by an Automatic Weather Station (AWS) at the Mt. Hunter site during the summer of 2013. Snow accumulation events are identified in the Mt. Hunter AWS dataset, and compared on a storm-by-storm basis to AWS data collected from the adjacent Kahiltna glacier 2000 m lower in elevation, and to regional National Weather Service (NWS) station data. We also evaluate the synoptic conditions associated with each Mt. Hunter accumulation event using NWS surface maps, NCEP-NCAR Reanalysis data, and the NOAA HYSPLIT back trajectory model. We categorize each Mt. Hunter accumulation event as pure snow accumulation, drifting, or blowing snow events based on snow accumulation, wind speed and temperature data using the method of Knuth et al (2009). We analyze the frequency and duration of events within each accumulation regime, in addition to the overall contribution of each event to the snowpack. Preliminary findings indicate that a majority of Mt. Hunter accumulation events are of pure accumulation nature (55.5%) whereas drifting (28.6%) and blowing (15.4%) snow events play a secondary role. Our results will characterize the local accumulation dynamics on Mt. Hunter and quantify the relationship between alpine micrometeorological and regional precipitation dynamics, providing key insights into the interpretation of the Mt. Hunter paleoprecipitation record.

Greenhouse Gas Laser Imaging Tomography Experiment (GreenLITE): Evaluation of a new method to look at high resolution spatial/temporal distributions of carbon over key sub km sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dobler, Jeremy; Zaccheo, T. Scott; Blume, Nathan

2015-01-01

Recently a new laser based approach for measuring area with potential for producing 2D estimates of the concentration spatial distribution has been developed through a cooperative agreement with the National Energy and Technology Laboratory of the Department of Energy, Exelis Inc. and AER Inc. The new approach is based on a pair of continuous wave intensity modulated laser absorption spectrometer transceivers, combined with a series of retro reflectors located around the perimeter of the area being monitored. The main goal of this cooperative agreement is monitoring, reporting and verification for ground carbon capture and storage projects. The system was recentlymore » tested at the Zero Emission Research and Technology site in Bozeman, MT, with underground leak rates ranging from 0.1 – 0.3 metric ton per day (T/d), as well as a 0.8 T/d surface release. Over 200 hours of data were collected over a rectangular grid 180m x 200m between August 18th and September 9th. In addition, multiple days of in situ data were acquired for the same site, using a Licor gas analyzer systems. Initial comparisons between the laser-based system and the in situ agree very well. The system is designed to operate remotely and transmit the data via a 3G/4G connection along with weather data for the site. An all web-based system ingests the data, populates a database, performs the inversion to ppm CO2 using the Line-by-Line Radiative Transfer Model (LBLRTM), and displays plots and statistics for the retrieved data. We will present an overview of the GreenLITE measurement system, outline the retrieval and reconstruction approach, and discuss results from extensive field testing.« less

The past, present and future of mitochondrial genomics: have we sequenced enough mtDNAs?

PubMed

Smith, David Roy

2016-01-01

The year 2014 saw more than a thousand new mitochondrial genome sequences deposited in GenBank-an almost 15% increase from the previous year. Hundreds of peer-reviewed articles accompanied these genomes, making mitochondrial DNAs (mtDNAs) the most sequenced and reported type of eukaryotic chromosome. These mtDNA data have advanced a wide range of scientific fields, from forensics to anthropology to medicine to molecular evolution. But for many biological lineages, mtDNAs are so well sampled that newly published genomes are arguably no longer contributing significantly to the progression of science, and in some cases they are tying up valuable resources, particularly journal editors and referees. Is it time to acknowledge that as a research community we have published enough mitochondrial genome papers? Here, I address this question, exploring the history, milestones and impacts of mitochondrial genomics, the benefits and drawbacks of continuing to publish mtDNAs at a high rate and what the future may hold for such an important and popular genetic marker. I highlight groups for which mtDNAs are still poorly sampled, thus meriting further investigation, and recommend that more energy be spent characterizing aspects of mitochondrial genomes apart from the DNA sequence, such as their chromosomal and transcriptional architectures. Ultimately, one should be mindful before writing a mitochondrial genome paper. Consider perhaps sending the sequence directly to GenBank instead, and be sure to annotate it correctly before submission. © The Author 2015. Published by Oxford University Press.

Matsubara-Takahashi cervix-holding technique for massive postpartum hemorrhage in patients with placenta previa with or without placenta accreta spectrum disorders.

PubMed

Takahashi, Hironori; Ohkuchi, Akihide; Usui, Rie; Suzuki, Hirotada; Baba, Yosuke; Matsubara, Shigeki

2018-03-01

To determine the efficacy and safety of the Matsubara-Takahashi cervix-holding technique (MT-holding) for achieving hemostasis for postpartum hemorrhage (PPH). The present retrospective observational study included data from deliveries that occurred between January 1, 2004, and December 31, 2014, at the Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Japan. Deliveries were included where patients experienced blood loss greater than 2500 mL and MT-holding was used. The success rates of the technique in patients with placenta accreta spectrum (PAS) disorders and PPH were determined; subsequent pregnancy outcomes were also examined. There were 53 deliveries included in the study; 29 patients had placenta previa and 8 of these patients also had PAS disorders. MT-holding achieved hemostasis in 15 (71%) and 4 (50%) patients with placenta previa without and with PAS disorders, respectively; the placenta was removed in the latter. Overall, MT-holding achieved hemostasis in 40 (75%) deliveries. Of nine patients who became pregnant after this procedure, six went on to have full-term deliveries. MT-holding achieved hemostasis in 50% of patients with PAS disorders and had an overall success rate of 75% for PPH, comparable to other uterus-sparing procedures. MT-holding is suggested as a simple, effective, safe technique available to less-experienced obstetrician; these findings require confirmation in larger studies. © 2017 International Federation of Gynecology and Obstetrics.

Interrelations Between Mitochondrial DNA Copy Number and Inflammation in Older Adults.

PubMed

Wu, I-Chien; Lin, Cheng-Chieh; Liu, Chin-San; Hsu, Chih-Cheng; Chen, Ching-Yu; Hsiung, Chao A

2017-07-01

Interplays between inflammation and mitochondrial biology are reported. Here, we examined the cross-sectional interrelationships of mitochondrial DNA copy number (mtDNACN) and inflammation and their interaction with physical functioning. A total of 1990 community-dwelling adults aged 65 years and older who were participating in the Healthy Aging Longitudinal Study in Taiwan underwent measurements of peripheral-blood leukocytes MtDNACN, multiple inflammatory markers, grip strength, and gait speed. Principal components analysis revealed two inflammatory factors: factor 1 (high-sensitivity C-reactive protein [hs-CRP], white blood cell count, fibrinogen and interleukin-6 [IL-6]); factor 2 (tumor necrosis factor receptor 1, D-dimer and soluble interleukin-6 receptor). Participants with severe physical functioning impairment (low grip strength and gait speed) had higher (p < .05) levels of factor 1 and 2, but not mtDNACN, than did those with moderately impaired (low grip strength or gait speed) and normal physical functioning. MtDNACN was negatively related to factor 1 (r = -.221, p < .001) but not factor 2 (r = -.002, p = .938). Increased factor 1 was strongly associated with higher odds of physical functioning impairment in those with a low mtDNACN (adjusted odds ratios [OR] of moderate physical function impairment 1.21, 95% CI 1.01-1.44; adjusted OR of severe physical function impairment 1.52, 95% CI 1.25-1.85) but not in those with a high mtDNACN (p for interaction = .016). A low mtDNACN was associated with an inflammation exhibiting elevated hs-CRP, IL-6, fibrinogen, and white blood cell count, and strengthened the association of this inflammation with physical functioning impairment. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Large Variation in the Ratio of Mitochondrial to Nuclear Mutation Rate across Animals: Implications for Genetic Diversity and the Use of Mitochondrial DNA as a Molecular Marker.

PubMed

Allio, Remi; Donega, Stefano; Galtier, Nicolas; Nabholz, Benoit

2017-11-01

It is commonly assumed that mitochondrial DNA (mtDNA) evolves at a faster rate than nuclear DNA (nuDNA) in animals. This has contributed to the popularity of mtDNA as a molecular marker in evolutionary studies. Analyzing 121 multilocus data sets and four phylogenomic data sets encompassing 4,676 species of animals, we demonstrate that the ratio of mitochondrial over nuclear mutation rate is highly variable among animal taxa. In nonvertebrates, such as insects and arachnids, the ratio of mtDNA over nuDNA mutation rate varies between 2 and 6, whereas it is above 20, on average, in vertebrates such as scaled reptiles and birds. Interestingly, this variation is sufficient to explain the previous report of a similar level of mitochondrial polymorphism, on average, between vertebrates and nonvertebrates, which was originally interpreted as reflecting the effect of pervasive positive selection. Our analysis rather indicates that the among-phyla homogeneity in within-species mtDNA diversity is due to a negative correlation between mtDNA per-generation mutation rate and effective population size, irrespective of the action of natural selection. Finally, we explore the variation in the absolute per-year mutation rate of both mtDNA and nuDNA using a reduced data set for which fossil calibration is available, and discuss the potential determinants of mutation rate variation across genomes and taxa. This study has important implications regarding DNA-based identification methods in predicting that mtDNA barcoding should be less reliable in nonvertebrates than in vertebrates. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Identification of an S-adenosylmethionine (SAM) dependent arsenic methyltransferase in Danio rerio

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamdi, Mohamad; Yoshinaga, Masafumi; Packianathan, Charles

2012-07-15

Arsenic methylation is an important cellular metabolic process that modulates arsenic toxicity and carcinogenicity. Biomethylation of arsenic produces a series of mono-, di- and tri-methylated arsenic metabolites that can be detected in tissues and excretions. Here we report that zebrafish exposed to arsenite (As{sup III}) produces organic arsenicals, including MMA{sup III}, MMA{sup V} and DMA{sup V} with characteristic tissue ratios, demonstrating that an arsenic methylation pathway exists in zebrafish. In mammals, cellular inorganic arsenic is methylated by a SAM-dependent arsenic methyltransferase, AS3MT. A zebrafish arsenic methyltransferase homolog, As3mt, was identified by sequence alignment. Western blotting analysis showed that As3mt wasmore » universally expressed in zebrafish tissues. Prominent expression in liver and intestine correlated with methylated arsenic metabolites detected in those tissues. As3mt was expressed in and purified from Escherichia coli for in vitro functional studies. Our results demonstrated that As3mt methylated As{sup III} to DMA{sup V} as an end product and produced MMA{sup III} and MMA{sup V} as intermediates. The activity of As3mt was inhibited by elevated concentrations of the substrate As{sup III} as well as the metalloid selenite, which is a well-known antagonistic micronutrient of arsenic toxicity. The activity As3mt was abolished by substitution of either Cys160 or Cys210, which corresponds to conserved cysteine residues in AS3MT homologs, suggesting that they are involved in catalysis. Expression in zebrafish of an enzyme that has a similar function to human and rodent orthologs in catalyzing intracellular arsenic biomethylation validates the applicability of zebrafish as a valuable vertebrate model for understanding arsenic-associated diseases in humans. -- Highlights: ► Zebrafish methylated As{sup III} to MMA{sup III}, MMA{sup V} and DMA{sup V}. ► A zebrafish arsenic methyltransferase (As3mt) was purified in E. coli. ► As3mt catalyzed biomethylation of As{sup III} to DMA{sup V} and produced toxic intermediates. ► As3mt activity is inhibited by elevated substrate concentrations and selenite. ► C160 and C165 are predicted as As{sup III} binding sites.« less

Synergistic effect of acupuncture and mirror therapy on post-stroke upper limb dysfunction: a study protocol for a randomized controlled trial.

PubMed

Xu, Ying; Lin, Shufang; Jiang, Cai; Ye, Xiaoqian; Tao, Jing; Wilfried, Schupp; Wong, Alex W K; Chen, Lidian; Yang, Shanli

2018-05-31

Upper limb dysfunction is common after stroke, posing an important challenge for post-stroke rehabilitation. The clinical efficacy of acupuncture for the recovery of post-stroke upper limb function has been previously demonstrated. Mirror therapy (MT) has also been found to be effective. However, the effects of acupuncture and MT have not been systematically compared. This trial aims to elucidate the synergistic effects of acupuncture and MT on upper limb dysfunction after stroke. A 2 × 2 factorial randomized controlled trial will be conducted at the rehabilitation hospitals affiliated with Fujian University of Traditional Chinese Medicine. A total of 136 eligible subjects will be randomly divided into acupuncture treatment (AT), MT, combined treatment, and control groups in a 1:1:1:1 ratio. All subjects will receive conventional treatment. The interventions will be performed 5 days per week for 4 weeks. AT, MT, and combined treatment will be performed for 30 min per day (combined treatment: AT 15 min + MT 15 min). The primary outcomes in this study will be the mean change in scores on both the FMA and WMFT from baseline to 4 weeks intervention and at 12 weeks follow-up between the two groups and within groups. The secondary outcomes are the mean change in the scores on the Visual Analogue Scale, Stroke Impact Scale, and modified Barthel index. Medical abstraction of adverse events will be assessed at each visit. The results of this trial will demonstrate the synergistic effect of acupuncture and MT on upper limb motor dysfunction after stroke. In addition, whether AT and MT, either combined or alone, are more effective than the conventional treatment in the management of post-stroke upper limb dysfunction will also be determined. Chinese Clinical Trial Registry: ChiCTR-IOR-17011118 . Registered on April 11, 2017. Version number: 01.2016.09.1.

The ROS-sensitive microRNA-9/9* controls the expression of mitochondrial tRNA-modifying enzymes and is involved in the molecular mechanism of MELAS syndrome.

PubMed

Meseguer, Salvador; Martínez-Zamora, Ana; García-Arumí, Elena; Andreu, Antonio L; Armengod, M-Eugenia

2015-01-01

Mitochondrial dysfunction activates mitochondria-to-nucleus signaling pathways whose components are mostly unknown. Identification of these components is important to understand the molecular mechanisms underlying mitochondrial diseases and to discover putative therapeutic targets. MELAS syndrome is a rare neurodegenerative disease caused by mutations in mitochondrial (mt) DNA affecting mt-tRNA(Leu(UUR)). Patient and cybrid cells exhibit elevated oxidative stress. Moreover, mutant mt-tRNAs(Leu(UUR)) lack the taurine-containing modification normally present at the wobble uridine (U34) of wild-type mt-tRNA(Leu(UUR)), which is considered an etiology of MELAS. However, the molecular mechanism is still unclear. We found that MELAS cybrids exhibit a significant decrease in the steady-state levels of several mt-tRNA-modification enzymes, which is not due to transcriptional regulation. We demonstrated that oxidative stress mediates an NFkB-dependent induction of microRNA-9/9*, which acts as a post-transcriptional negative regulator of the mt-tRNA-modification enzymes GTPBP3, MTO1 and TRMU. Down-regulation of these enzymes by microRNA-9/9* affects the U34 modification status of non-mutant tRNAs and contributes to the MELAS phenotype. Anti-microRNA-9 treatments of MELAS cybrids reverse the phenotype, whereas miR-9 transfection of wild-type cells mimics the effects of siRNA-mediated down-regulation of GTPBP3, MTO1 and TRMU. Our data represent the first evidence that an mt-DNA disease can directly affect microRNA expression. Moreover, we demonstrate that the modification status of mt-tRNAs is dynamic and that cells respond to stress by modulating the expression of mt-tRNA-modifying enzymes. microRNA-9/9* is a crucial player in mitochondria-to-nucleus signaling as it regulates expression of nuclear genes in response to changes in the functional state of mitochondria. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Exercise and manual physiotherapy arthritis research trial (EMPART) for osteoarthritis of the hip: a multicenter randomized controlled trial.

PubMed

French, Helen P; Cusack, Tara; Brennan, Aisling; Caffrey, Aoife; Conroy, Ronán; Cuddy, Vanessa; FitzGerald, Oliver M; Fitzpatrick, Martina; Gilsenan, Clare; Kane, David; O'Connell, Paul G; White, Breon; McCarthy, Geraldine M

2013-02-01

To determine the effectiveness of exercise therapy (ET) compared with ET with adjunctive manual therapy (MT) for people with hip osteoarthritis (OA); and to identify if immediate commencement of treatment (ET or ET+MT) was more beneficial than a 9-week waiting period for either intervention. Assessor-blind randomized controlled trial with a 9-week and 18-week follow-up. Four academic teaching hospitals in Dublin, Ireland. Patients (N=131) with hip OA recruited from general practitioners, rheumatologists, orthopedic surgeons, and other hospital consultants were randomized to 1 of 3 groups: ET (n=45), ET+MT (n=43), and waitlist controls (n=43). Participants in both the ET and ET+MT groups received up to 8 treatments over 8 weeks. Control group participants were rerandomized into either ET or ET+MT groups after 9 week follow-up. Their data were pooled with original treatment group data: ET (n=66) and ET+MT (n=65). The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function (PF) subscale. Secondary outcomes included physical performance, pain severity, hip range of motion (ROM), anxiety/depression, quality of life, medication usage, patient-perceived change, and patient satisfaction. There was no significant difference in WOMAC PF between the ET (n=66) and ET+MT (n=65) groups at 9 weeks (mean difference, .09; 95% confidence interval [CI] -2.93 to 3.11) or 18 weeks (mean difference, .42; 95% CI, -4.41 to 5.25), or between other outcomes, except patient satisfaction with outcomes, which was higher in the ET+MT group (P=.02). Improvements in WOMAC, hip ROM, and patient-perceived change occurred in both treatment groups compared with the control group. Self-reported function, hip ROM, and patient-perceived improvement occurred after an 8-week program of ET for patients with OA of the hip. MT as an adjunct to exercise provided no further benefit, except for higher patient satisfaction with outcome. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Correlation Between Cycling Power and Muscle Thickness in Cyclists.

PubMed

Lee, Hyung-Jin; Lee, Kang-Woo; Lee, Yong-Woo; Kim, Hee-Jin

2018-05-17

The aim of this study was to determine the correlation between muscle thickness (MT) and cycling power in varsity cyclists using ultrasonography (US) and to identify any differences in MT between short- and long-distance cyclists. Twelve cyclists participated in this study. Real-time two-dimensional B-mode US was used to measure the MT in the anterior thigh, anterior lower leg, and trunk, especially in the abdominal and lumbar regions. A Wattbike cycle ergometer was used to measure cycling power parameters such as maximum anaerobic power (over 5 s), mean anaerobic power (over 30 s), and aerobic power (over 3 min). This study was approved by the Ethics Committee of Korea National Sports University. There was a significant relationship between the MT and cycling power for the rectus femoris (RF) and vastus lateralis (VL) in the thigh, the rectus abdominis (RA) in the abdominal region, and the erector spinae (ES) in the lower back. The MT values of the RF, VL, and ES were strongly associated with the maximum and mean anaerobic power. There were significant differences between short- and long-distance cyclists in the MT of the RF in the thigh, the RA, the external abdominal oblique, the internal abdominal oblique, and the transverse abdominis muscle in the abdomen. We suggest that training programs attempting to improve cycling performance focus on improving the VL and ES via resistance weight or cycle training and also the core muscles for short-distance cyclists. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Observing Two Important Teaching Variables.

ERIC Educational Resources Information Center

Gustafson, John A.

1986-01-01

Two behaviors essential to good teaching, teacher expectation and teacher flexibility, have been incorporated into the observation system used in the student teacher program at the University of New Mexico. The importance of these behaviors in teaching and in evaluating student teachers is discussed. (MT)

Critical Thinking or Cony Cozenage.

ERIC Educational Resources Information Center

Matulich, Loretta

Teachers of history, introductory chemistry, and literature from Portland State University, Portland Community College, Clark College, Mt. Hood Community College, and Clackamas Community College (Oregon) have been working together to foster critical thinking in their students. Teachers in these disciplines have been meeting at their respective…

Meet the Alpha-Pets.

ERIC Educational Resources Information Center

Zitlaw, Jo Ann Bruce; Frank, Cheryl Standish

1985-01-01

"Alpha-Pets" are the focal point of an integrated, multidisciplinary curriculum. Each pet is featured for a week in a vocabulary-rich story and introduces related activities beginning with the featured letter, such as the four food groups during Freddie Fish's week or universe during Ulysses Unicorn's week. (MT)

Educational Policy Studies: Old Wine in a New Bottle.

ERIC Educational Resources Information Center

Eisele, Chris

1985-01-01

As educational policy studies have multiplied, Illinois State University's (ISU) Educational Administration and Foundations Department developed a new series of policy studies grounded in historical and philosophical methodology. Content of one course is described, and benefits of the ISU model are discussed. (MT)

Education and the Religious.

ERIC Educational Resources Information Center

Vandenberg, Donald

1987-01-01

This article attempts to emancipate the religious aspect of human existence from its accidental, historical embodiment in religions. The religious concerns being at home in nature, on earth, and in the universe. Ways of teaching this natural piety in a manner not connected with religion are discussed. (MT)

The stink bugs (Hemiptera: Heteroptera: Pentatomidae) of Washington state

USDA-ARS?s Scientific Manuscript database

Froeschner (1988) records 23 species of stink bugs (Hemiptera: Heteroptera: Pentatomidae) as occurring in Washington state. Based onmaterial primarily housed in the M.T. James Entomological Collection at Washington State University, the number of species is increased to 47. Species recorded by Froes...

Using Reanalysis to Provide Circulation Context for Ice Cores Recovered from Mt. Hunter Plateau in Denali National Park

NASA Astrophysics Data System (ADS)

Osterberg, E. C.; Birkel, S. D.; Kreutz, K. J.; Wake, C. P.; Campbell, S. W.; Winski, D.

2015-12-01

Researchers from the University of Maine, University of New Hampshire, and Dartmouth College supported by NSF recently recovered two ice cores from the Mt. Hunter Plateau in the Alaska Range of Denali National Park. Ongoing analyses of snow accumulation, snowmelt, stable isotopes, and chemistry within the core are providing proxy information for ~1000 years of regional climate variability. Broader context to link circulation across the North Pacific and western North America can be obtained by using climate reanalysis. In this vein, we are using monthly, daily, and sub-daily meteorological fields from the NCEP Climate Forecasting System Reanalysis (CFSR) to characterize large-scale circulation associated with notable events in the ice core record onward from 1979. One goal is to assess the relationship between annual snow accumulation spikes and storm frequency and magnitude. A second goal is to relate these observations to events during the Little Ice Age and Medieval Warm Period. Work is in progress, and results will be presented at the fall meeting.

Positive contribution of pathogenic mutations in the mitochondrial genome to the promotion of cancer by prevention from apoptosis.

PubMed

Shidara, Yujiro; Yamagata, Kumi; Kanamori, Takashi; Nakano, Kazutoshi; Kwong, Jennifer Q; Manfredi, Giovanni; Oda, Hideaki; Ohta, Shigeo

2005-03-01

The role of mitochondrial dysfunction in cancer has been a subject of great interest and much ongoing investigation. Although most cancer cells harbor somatic mutations in mitochondrial DNA (mtDNA), the question of whether such mutations contribute to the promotion of carcinomas remains unsolved. Here we used trans-mitochondrial hybrids (cybrids) containing a common HeLa nucleus and mtDNA of interest to compare the role of mtDNA against the common nuclear background. We constructed cybrids with or without a homoplasmic pathogenic point mutation at nucleotide position 8,993 or 9,176 in the mtDNA ATP synthase subunit 6 gene (MTATP6) derived from patients with mitochondrial encephalomyopathy. When the cybrids were transplanted into nude mice, the MTATP6 mutations conferred an advantage in the early stage of tumor growth. The mutant cybrids also increased faster than wild type in culture. To complement the mtDNA mutations, we transfected a wild-type nuclear version of MTATP, whose codons were converted to the universal genetic codes containing a mitochondrial target sequence, into the nucleus of cybrids carrying mutant MTATP6. The restoration of MTATP slowed down the growth of tumor in transplantation. Conversely, expression of a mutant nuclear version of MTATP6 in the wild-type cybrids declined respiration and accelerated the tumor growth. These findings showed that the advantage in tumor growth depended upon the MTATP6 function but was not due to secondary nuclear mutations caused by the mutant mitochondria. Because apoptosis occurred less frequently in the mutant versus wild-type cybrids in cultures and tumors, the pathogenic mtDNA mutations seem to promote tumors by preventing apoptosis.

The role of the mitochondrial ribosome in human disease: searching for mutations in 12S mitochondrial rRNA with high disruptive potential

PubMed Central

Smith, Paul M.; Elson, Joanna L.; Greaves, Laura C.; Wortmann, Saskia B.; Rodenburg, Richard J.T.; Lightowlers, Robert N.; Chrzanowska-Lightowlers, Zofia M.A.; Taylor, Robert W.; Vila-Sanjurjo, Antón

2014-01-01

Mutations of mitochondrial DNA are linked to many human diseases. Despite the identification of a large number of variants in the mitochondrially encoded rRNA (mt-rRNA) genes, the evidence supporting their pathogenicity is, at best, circumstantial. Establishing the pathogenicity of these variations is of major diagnostic importance. Here, we aim to estimate the disruptive effect of mt-rRNA variations on the function of the mitochondrial ribosome. In the absence of direct biochemical methods to study the effect of mt-rRNA variations, we relied on the universal conservation of the rRNA fold to infer their disruptive potential. Our method, named heterologous inferential analysis or HIA, combines conservational information with functional and structural data obtained from heterologous ribosomal sources. Thus, HIA's predictive power is superior to the traditional reliance on simple conservation indexes. By using HIA, we have been able to evaluate the disruptive potential for a subset of uncharacterized 12S mt-rRNA variations. Our analysis revealed the existence of variations in the rRNA component of the human mitoribosome with different degrees of disruptive power. In cases where sufficient information regarding the genetic and pathological manifestation of the mitochondrial phenotype is available, HIA data can be used to predict the pathogenicity of mt-rRNA mutations. In other cases, HIA analysis will allow the prioritization of variants for additional investigation. Eventually, HIA-inspired analysis of potentially pathogenic mt-rRNA variations, in the context of a scoring system specifically designed for these variants, could lead to a powerful diagnostic tool. PMID:24092330

Absence of a Universal Mechanism of Mitochondrial Toxicity by Nucleoside Analogs▿

PubMed Central

Lund, Kaleb C.; Peterson, LaRae L.; Wallace, Kendall B.

2007-01-01

Nucleoside analogs are associated with various mitochondrial toxicities, and it is becoming increasingly difficult to accommodate these differences solely in the context of DNA polymerase gamma inhibition. Therefore, we examined the toxicities of zidovudine (AZT) (10 and 50 μM; 2.7 and 13.4 μg/ml), didanosine (ddI) (10 and 50 μM; 2.4 and 11.8 μg/ml), and zalcitabine (ddC) (1 and 5 μM; 0.21 and 1.1 μg/ml) in HepG2 and H9c2 cells without the presumption of mitochondrial DNA (mtDNA) depletion. Ethidium bromide (EtBr) (0.5 μg/ml; 1.3 μM) was used as a positive control. AZT treatment resulted in metabolic disruption (increased lactate and superoxide) and increased cell mortality with decreased proliferation, while mtDNA remained unchanged or increased (HepG2 cells; 50 μM AZT). ddC caused pronounced mtDNA depletion in HepG2 cells but not in H9c2 cells and increased mortality in HepG2 cells, but no significant metabolic disruption in either cell type. ddI caused a moderate depletion of mtDNA in both cell types but showed no other effects. EtBr exposure resulted in metabolic disruption, increased cell mortality with decreased cell proliferation, and mtDNA depletion in both cell types. We conclude that nucleoside analogs display unique toxicities within and between culture models, and therefore, care should be taken when generalizing about the mechanisms of nucleoside reverse transcriptase inhibitor toxicity. Additionally, mtDNA abundance does not necessarily correlate with metabolic disruption, especially in cell culture; careful discernment is recommended in this regard. PMID:17470651

Absence of a universal mechanism of mitochondrial toxicity by nucleoside analogs.

PubMed

Lund, Kaleb C; Peterson, LaRae L; Wallace, Kendall B

2007-07-01

Nucleoside analogs are associated with various mitochondrial toxicities, and it is becoming increasingly difficult to accommodate these differences solely in the context of DNA polymerase gamma inhibition. Therefore, we examined the toxicities of zidovudine (AZT) (10 and 50 microM; 2.7 and 13.4 microg/ml), didanosine (ddI) (10 and 50 microM; 2.4 and 11.8 microg/ml), and zalcitabine (ddC) (1 and 5 microM; 0.21 and 1.1 microg/ml) in HepG2 and H9c2 cells without the presumption of mitochondrial DNA (mtDNA) depletion. Ethidium bromide (EtBr) (0.5 microg/ml; 1.3 microM) was used as a positive control. AZT treatment resulted in metabolic disruption (increased lactate and superoxide) and increased cell mortality with decreased proliferation, while mtDNA remained unchanged or increased (HepG2 cells; 50 microM AZT). ddC caused pronounced mtDNA depletion in HepG2 cells but not in H9c2 cells and increased mortality in HepG2 cells, but no significant metabolic disruption in either cell type. ddI caused a moderate depletion of mtDNA in both cell types but showed no other effects. EtBr exposure resulted in metabolic disruption, increased cell mortality with decreased cell proliferation, and mtDNA depletion in both cell types. We conclude that nucleoside analogs display unique toxicities within and between culture models, and therefore, care should be taken when generalizing about the mechanisms of nucleoside reverse transcriptase inhibitor toxicity. Additionally, mtDNA abundance does not necessarily correlate with metabolic disruption, especially in cell culture; careful discernment is recommended in this regard.

Role of p53, Mitochondrial DNA Deletions, and Paternal Age in Autism: A Case-Control Study

PubMed Central

Wong, Sarah; Napoli, Eleonora; Krakowiak, Paula; Tassone, Flora; Hertz-Picciotto, Irva

2016-01-01

BACKGROUND: The tumor suppressor p53 responds to a variety of environmental stressors by regulating cell cycle arrest, apoptosis, senescence, DNA repair, bioenergetics and mitochondrial DNA (mtDNA) copy number maintenance. Developmental abnormalities have been reported in p53-deficient mice, and altered p53 and p53-associated pathways in autism (AU). Furthermore, via the Pten-p53 crosstalk, Pten haploinsufficient-mice have autisticlike behavior accompanied by brain mitochondrial dysfunction with accumulation of mtDNA deletions. METHODS: mtDNA copy number and deletions, and p53 gene copy ratios were evaluated in peripheral blood monocytic cells from children aged 2–5 years with AU (n = 66), race-, gender-, and age-matched typically neurodeveloping children (n = 46), and both parents from each diagnostic group, recruited by the Childhood Autism Risk from Genes and Environment study at the University of California, Davis. RESULTS: mtDNA deletions and higher p53 gene copy ratios were more common in children with AU and their fathers. The incidence of mtDNA deletions in fathers of children with AU was increased 1.9-fold over fathers of typically neurodeveloping children, suggesting a role for deficient DNA repair capacity not driven by paternal age. Deletions in mtDNA and altered p53 gene copy ratios seem to result from genetics (children with severity scores ≥8) and/or act in concert with environmental factors (children with 6–7 severity scores). CONCLUSIONS: Given pro- and antioxidant activities of p53, and associations of genomic instability with disorders other than AU, our study suggests a link between DNA repair capacity, genomic instability in the 17p13.1 region influenced by environmental triggers, and AU diagnosis. PMID:27033107

Pain relief effect of breast feeding and music therapy during heel lance for healthy-term neonates in China: a randomized controlled trial.

PubMed

Zhu, Jiemin; Hong-Gu, He; Zhou, Xiuzhu; Wei, Haixia; Gao, Yaru; Ye, Benlan; Liu, Zuguo; Chan, Sally Wai-Chi

2015-03-01

to test the effectiveness of breast feeding (BF), music therapy (MT), and combined breast feeding and music therapy (BF+MT) on pain relief in healthy-term neonates during heel lance. randomised controlled trial. in the postpartum unit of one university-affiliated hospital in China from August 2013 to February 2014. among 288 healthy-term neonates recruited, 250 completed the trial. All neonates were undergoing heel lancing for metabolic screening, were breast fed, and had not been fed for the previous 30 minutes. all participants were randomly assigned into four groups - BF, MT, BF+MT, and no intervention - with 72 neonates in each group. Neonates in the control group received routine care. Neonates in the other three intervention groups received corresponding interventions five minutes before the heel lancing and throughout the whole procedure. Neonatal Infant Pain Scale (NIPS), latency to first cry, and duration of first crying. mean changes in NIPS scores from baseline over time was dependent on the interventions given. Neonates in the BF and combined BF+MT groups had significantly longer latency to first cry, shorter duration of first crying, and lower pain mean score during and one minute after heel lance, compared to the other two groups. No significant difference in pain response was found between BF groups with or without music therapy. The MT group did not achieve a significantly reduced pain response in all outcome measures. BF could significantly reduce pain response in healthy-term neonates during heel lance. MT did not enhance the effect of pain relief of BF. healthy-term neonates should be breast fed to alleviate pain during heel lance. There is no need for the additional input of classical music on breast feeding in clinic to relieve procedural pain. Nurses should encourage breast feeding to relieve pain during heel lance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Metallothionein MT2A A-5G Polymorphism as a Risk Factor for Chronic Kidney Disease and Diabetes: Cross-Sectional and Cohort Studies.

PubMed

Hattori, Yuta; Naito, Mariko; Satoh, Masahiko; Nakatochi, Masahiro; Naito, Hisao; Kato, Masashi; Takagi, Sahoko; Matsunaga, Takashi; Seiki, Toshio; Sasakabe, Tae; Suma, Shino; Kawai, Sayo; Okada, Rieko; Hishida, Asahi; Hamajima, Nobuyuki; Wakai, Kenji

2016-07-01

Metallothioneins (MTs) are proteins that protect cells from toxic agents such as heavy metal ions or reactive oxygen species. MT2A A-5G is a single nucleotide polymorphism in the promoter region of the MT2A gene, and the minor G allele results in lower transcription efficiency. We aimed to elucidate associations between MT2A A-5G and risks of 2 diseases potentially related to lowered MT expression, chronic kidney disease (CKD), and diabetes mellitus (DM), in a community-dwelling population. Study subjects were Nagoya city residents participating in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC) Daiko Study, comprised 749 men and 2,025 women, aged 39-75 years. CKD (>stage 3) and DM were defined by standard guidelines. Associations were evaluated using logistic regression models with adjustments for age, sex and potential confounders in a cross-sectional study, and verified in a 5-year longitudinal study. Odds ratios (OR [95% confidence interval]) were calculated relative to the AA genotype. Serum MT (I + II), Cd and zinc levels were also determined by genotype. The OR of the GG genotype for CKD risk was 3.98 (1.50, 10.58) in the cross-sectional study and 5.17 (1.39, 19.28) in the longitudinal study. The OR of the GA genotype for DM was 1.86 (1.26, 2.75) in the cross-sectional study and 2.03 (1.19, 3.46) in the longitudinal study. MT2A A-5G may be associated with CKD and DM risks. This polymorphism is a promising target for evaluations of CKD and DM risks with possible involvement of low-dose chronic exposure to environmental pollutants. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

Mod3DMT and EMTF: Free Software for MT Data Processing and Inversion

NASA Astrophysics Data System (ADS)

Egbert, G. D.; Kelbert, A.; Meqbel, N. M.

2017-12-01

"ModEM" was developed at Oregon State University as a modular system for inversion of electromagnetic (EM) geophysical data (Egbert and Kelbert, 2012; Kelbert et al., 2014). Although designed for more general (frequency domain) EM applications, and originally intended as a testbed for exploring inversion search and regularization strategies, our own initial uses of ModEM were for 3-D imaging of the deep crust and upper mantle at large scales. Since 2013 we have offered a version of the source code suitable for 3D magnetotelluric (MT) inversion on an "as is, user beware" basis for free for non-commercial applications. This version, which we refer to as Mod3DMT, has since been widely used by the international MT community. Over 250 users have registered to download the source code, and at least 50 MT studies in the refereed literature, covering locations around the globe at a range of spatial scales, cite use of ModEM for 3D inversion. For over 30 years I have also made MT processing software available for free use. In this presentation, I will discuss my experience with these freely available (but perhaps not truly open-source) computer codes. Although users are allowed to make modifications to the codes (on conditions that they provide a copy of the modified version) only a handful of users have tried to make any modification, and only rarely are modifications even reported, much less provided back to the developers.

Symmetry and topology code of the cluster self-assembly of framework MT structures of alumophosphates AlPO4(H2O)2 (metavariscite and variscite) and Al2(PO4)2(H2O)3 (APC)

NASA Astrophysics Data System (ADS)

Ilyushin, G. D.; Blatov, V. A.

2017-03-01

The supramolecular chemistry of alumophosphates, which form framework 3D MT structures from polyhedral AlO4(H2O)2 clusters with octahedral O coordination (of M polyhedra) and PO4 and AlO4 with tetrahedral O coordination (of T polyhedra), is considered. A combinatorial-topological modeling of the formation of possible types of linear (six types) and ring (two types) tetrapolyhedral cluster precursors M2T2 from MT monomers is carried out. Different versions of chain formation from linked (MT)2 rings (six types) are considered. The model, which has a universal character, has been used to simulate the cluster selfassembly of the crystal structure of AlPO4(H2O)2 minerals (metavariscite, m-VAR, and variscite, VAR) and zeolite [Al2(PO4)2(H2O)2] · H2O (APC). A tetrapolyhedral linear precursor is established for m-VAR and a ring precursor (MT)2 is established for VAR and APC. The symmetry and topology code of the processes of crystal structure self-assembly from cluster precursors is completely reconstructed. The functional role of the O-H···O hydrogen bonds is considered for the first time. The cluster self-assembly model explains the specific features of the morphogenesis of single crystals: m-VAR prisms, flattened VAR octahedra, and needleshaped APC square-base prisms.

Molecular testing in lung cancer: fine-needle aspiration specimen adequacy and test prioritization prior to the CAP/IASLC/AMP Molecular Testing Guideline publication.

PubMed

Rafael, Oana C; Aziz, Mohamed; Raftopoulos, Harry; Vele, Oana E; Xu, Weisheng; Sugrue, Chiara

2014-06-01

Subtyping of lung carcinoma with immunohistochemistry is essential for diagnosis, whereas molecular testing (MT) is required for therapy guidance. In the current study, the authors report on MT performed on fine-needle aspiration specimens at the study institution over a 2-year period preceding the April 2013 College of American Pathologists (CAP)/International Association for the Study of Lung Cancer (IASLC)/Association for Molecular Pathology (AMP) Molecular Testing Guideline (MTG) publication. The database of the study institution was retrospectively queried for cases of lung and thoracic/lower cervical lymph node fine-needle aspiration specimens for 2011 through 2012. Of 246 selected cases, 26 featured a limited amount of material in cell blocks. MT increased significantly between 2011 and 2012 and was requested in 39.4% of cases (97 of 246 cases): 86 of those cases had at least 1 MT result and 11 had insufficient material for any MT. Anaplastic lymphoma kinase (ALK) testing was performed in 9 cases in which DNA was insufficient for epidermal growth factor receptor (EGFR) testing. In addition, 13 cases of adenocarcinoma/non-small cell lung carcinoma had at least 1 MT canceled because of insufficient DNA, but at the same time had an average of 3.46 immunohistochemical stains performed. Of all the cytology specimens, 10.6% featured limited material; however, no universally accepted testing sequence priority was available at the time the study was performed. As per the MTG, MT should take precedence over immunohistochemistry in cases of adenocarcinoma/non-small cell lung carcinoma. Approximately 5.3% of the specimens in the current study had insufficient material for MT while having multiple stains performed instead. The MTG also recommend performing EGFR before ALK testing; the authors found 9 cases with insufficient material for EGFR testing that had ALK testing performed. The results of the current study underscore the need for a testing prioritization algorithm in view of the MTG publication to serve as reference for both clinicians and pathologists. © 2014 American Cancer Society.

The Exercise Physiology Laboratory--A Source of Health Promotion.

ERIC Educational Resources Information Center

Norris, William; Norred, Robert

1988-01-01

A visit to the Exercise Physiology Laboratory at the University of Tennessee is part of a physical education class required of all undergraduate students. The laboratory demonstration stimulates student interest and enrollment in physical education. Benefits to students, the laboratory, and the school are described. (MT)

A Game Plan for Ending the Minority Teacher Shortage.

ERIC Educational Resources Information Center

Hatton, Barbara R.

1988-01-01

The 1980s have been a period of stable or declining numbers and proportions of minority students in colleges and universities. There has been a sharp drop in the number of Black and other minority education graduates. Ways of reversing this trend are addressed. (MT)

Structurally Controlled Geothermal Systems in the Central Cascades Arc-Backarc Regime, Oregon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wannamaker, Philip E.

The goal of this project has been to analyze available magnetotelluric (MT) geophysical surveys, structural geology based on mapping and LiDAR, and fluid geochemical data, to identify high-temperature fluid upwellings, critically stressed rock volumes, and other evidence of structurally-controlled geothermal resources. Data were to be integrated to create conceptual models of volcanic-hosted geothermal resources along the Central Cascades arc segment, especially in the vicinity of Mt. Jefferson to Three Sisters. LiDAR data sets available at Oregon State University (OSU) allowed detailed structural geology modeling through forest canopy. Copious spring and well fluid chemistries, including isotopes, were modeled using Geo-T andmore » TOUGHREACT software.« less

OptFuels: Fuel treatment optimization

Treesearch

Greg Jones

2011-01-01

Scientists at the USDA Forest Service, Rocky Mountain Research Station, in Missoula, MT, in collaboration with scientists at the University of Montana, are developing a tool to help forest managers prioritize forest fuel reduction treatments. Although several computer models analyze fuels and fire behavior, stand-level effects of fuel treatments, and priority planning...

Inflight observation of Bottlinger's rings.

PubMed

Shaw, Joseph A

2017-07-01

On the morning of 5 November 2013, a bright subsun was consistently visible during a flight from Bozeman, Montana, to Salt Lake City, Utah. Just after passing over the Wasatch Mountains and beginning to descend into the Salt Lake Valley, the subsun expanded to a rare display of Bottlinger's rings-an elliptical halo surrounding the subsun. The rings remained visible for 1 to 2 min. This paper shows photographs of the sequence, along with meteorological data from a nearby radiosonde. The display occurred in virga below clouds at an air temperature in the approximate range from -8°C to -12°C, in air saturated with respect to ice, at an altitude of approximately 2600-3600 m above mean sea level.

Mode identification from spectroscopy of gravity-mode pulsators

NASA Astrophysics Data System (ADS)

Pollard, K. R.; Brunsden, E.; Cottrell, P. L.; Davie, M.; Greenwood, A.; Wright, D. J.; De Cat, P.

2014-02-01

The gravity modes present in γ Doradus stars probe the deep stellar interiors and are thus of particular interest in asteroseismology. For the MUSICIAN programme at the University of Canterbury, we obtain extensive high-resolution echelle spectra of γ Dor stars from the Mt John University Observatory in New Zealand. We analyze these to obtain the pulsational frequencies and identify these with the multiple pulsational modes excited in the star. A summary of recent results from our spectroscopic mode-identification programme is given.

Maternal Lifetime Stress and Prenatal Psychological Functioning and Decreased Placental Mitochondrial DNA Copy Number in the PRISM Study.

PubMed

Brunst, Kelly J; Sanchez Guerra, Marco; Gennings, Chris; Hacker, Michele; Jara, Calvin; Bosquet Enlow, Michelle; Wright, Robert O; Baccarelli, Andrea; Wright, Rosalind J

2017-12-01

Psychosocial stress contributes to placental oxidative stress. Mitochondria are vulnerable to oxidative stress, which can lead to changes in mitochondrial DNA copy number (mtDNAcn). We examined associations of maternal lifetime stress, current negative life events, and depressive and posttraumatic-stress-disorder symptom scores with placental mtDNAcn in a racially/ethnically diverse sample (n = 147) from the Programming of Intergenerational Stress Mechanisms (PRISM) study (Massachusetts, March 2011 to August 2012). In linear regression analyses adjusted for maternal age, race/ethnicity, education, prenatal fine particulate matter exposure, prenatal smoking exposure, and the sex of the child, all measures of stress were associated with decreased placental mtDNAcn (all P values < 0.05). Weighted-quantile-sum (WQS) regression showed that higher lifetime stress and depressive symptoms accounted for most of the effect on mtDNAcn (WQS weights: 0.25 and 0.39, respectively). However, among white individuals, increased lifetime stress and posttraumatic stress disorder symptoms explained the majority of the effect (WQS weights: 0.20 and 0.62, respectively) while among nonwhite individuals, lifetime stress and depressive symptoms accounted for most of the effect (WQS weights: 0.27 and 0.55, respectively). These analyses are first to link increased maternal psychosocial stress with reduced placental mtDNAcn and add to literature documenting racial/ethnic differences in the psychological sequelae of chronic stress that may contribute to maternal-fetal health. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A comparison of 15 Hz sine on-line and off-line magnetic stimulation affecting the voltage-gated sodium channel currents of prefrontal cortex pyramidal neurons

NASA Astrophysics Data System (ADS)

Zheng, Yu; Dong, Lei; Gao, Yang; Dou, Jun-Rong; Li, Ze-yan

2016-10-01

Combined with the use of patch-clamp techniques, repetitive transcranial magnetic stimulation (rTMS) has proven to be a noninvasive neuromodulation tool that can inhibit or facilitate excitability of neurons after extensive research. The studies generally focused on the method: the neurons are first stimulated in an external standard magnetic exposure device, and then moved to the patch-clamp to record electrophysiological characteristics (off-line magnetic exposure). Despite its universality, real-time observation of the effects of magnetic stimulation on the neurons is more effective (on-line magnetic stimulation). In this study, we selected a standard exposure device for magnetic fields acting on mouse prefrontal cortex pyramidal neurons, and described a new method that a patch-clamp setup was modified to allow on-line magnetic stimulation. By comparing the off-line exposure and on-line stimulation of the same magnetic field intensity and frequency affecting the voltage-gated sodium channel currents, we succeeded in proving the feasibility of the new on-line stimulation device. We also demonstrated that the sodium channel currents of prefrontal cortex pyramidal neurons increased significantly under the 15 Hz sine 1 mT, and 2 mT off-line magnetic field exposure and under the 1 mT and 2 mT on-line magnetic stimulation, and the rate of acceleration was most significant on 2 mT on-line magnetic stimulation. This study described the development of a new on-line magnetic stimulator and successfully demonstrated its practicability for scientific stimulation of neurons.

Structural analysis of the PSD-95 cluster by electron tomography and CEMOVIS: a proposal for the application of the genetically encoded metallothionein tag.

PubMed

Hirabayashi, Ai; Fukunaga, Yuko; Miyazawa, Atsuo

2014-06-01

Postsynaptic density-95 (PSD-95) accumulates at excitatory postsynapses and plays important roles in the clustering and anchoring of numerous proteins at the PSD. However, a detailed ultrastructural analysis of clusters exclusively consisting of PSD-95 has never been performed. Here, we employed a genetically encoded tag, three tandem repeats of metallothionein (3MT), to study the structure of PSD-95 clusters in cells by electron tomography and cryo-electron microscopy of vitreous sections. We also performed conventional transmission electron microscopy (TEM). Cultured hippocampal neurons expressing a fusion protein of PSD-95 coupled to 3MT (PDS-95-3MT) were incubated with CdCl2 to result in the formation of Cd-bound PSD-95-3MT. Two types of electron-dense deposits composed of Cd-bound PSD-95-3MT were observed in these cells by TEM, as reported previously. Electron tomography revealed the presence of membrane-shaped structures representing PSD-95 clusters at the PSD and an ellipsoidal structure located in the non-synaptic cytoplasm. By TEM, the PSD-95 clusters appeared to be composed of a number of dense cores. In frozen hydrated sections, these dense cores were also found beneath the postsynaptic membrane. Taken together, our findings suggest that dense cores of PSD-95 aggregate to form the larger clusters present in the PSD and the non-synaptic cytoplasm. © The Author 2014. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Analyzing Population Genetics Using the Mitochondrial Control Region and Bioinformatics

ERIC Educational Resources Information Center

Sato, Takumi; Phillips, Bonnie; Latourelle, Sandra M.; Elwess, Nancy L.

2010-01-01

The 14-base pair hypervariable region in mitochondrial DNA (mtDNA) of Asian populations, specifically Japanese and Chinese students at Plattsburgh State University, was examined. Previous research on this 14-base pair region showed it to be susceptible to mutations and as a result indicated direct correlation with specific ethnic populations.…

Interlingual Machine Translation: Prospects and Setbacks

ERIC Educational Resources Information Center

Acikgoz, Firat; Sert, Olcay

2006-01-01

This study, in an attempt to rise above the intricacy of "being informed on the verge of globalization," is founded on the premise that Machine Translation (MT) applications searching for an ideal key to find a universal foundation for all natural languages have a restricted say over the translation process at various discourse levels. Our paper…

76 FR 35010 - Notice of Inventory Completion: Colorado Historical Society (History Colorado), Denver, CO

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-15

... remains representing a minimum of 10 individuals were removed from Pock's Garden Site (5MT.10851), in.... Jennings, the Colorado State University (CSU) Field School, investigated and transferred the individuals to... and under the direction of Mona Charles, Director of the Archaeological Field School. The site is...

Evaluating wildlife mortality hotspots, habitat connectivity and potential accommodation along US 287 and MT 87 in the Madison Valley, Montana, final report.

DOT National Transportation Integrated Search

2016-11-01

The Western Transportation Institute at Montana State University (WTI) and the Craighead Institute (ChI) conducted a two-year study to investigate the effect of the major highways in the Madison Valley on road-related wildlife mortality and movement ...

Shared Skies Partnership: A Dual-Site All-Sky Live Remote Observing Initiative for Research and Education

NASA Astrophysics Data System (ADS)

Kielkopf, John F.; Hart, R.; Carter, B.; Collins, K. A.; Brown, C.; Hay, J.; Hons, A.; Marsden, S.

2014-01-01

The University of Southern Queensland's Mt. Kent Observatory in Queensland, Australia, and the University of Louisville's Moore Observatory in Kentucky, USA, are collaborating in the development of live remote observing for research, student training, and education. With a focus on flexible operation assisted by semi-autonomous controllers, rather than completely robotic data acquisition, the partnership provides interactive hands-on experience to students at all levels, optimized performance based on real-time observations, and flexible scheduling for transient events and targets of opportunity. Two sites on opposites sides of the globe cover the entire sky, and for equatorial regions allow nearly continuous coverage. The facilites include 0.5-m corrected Dall-Kirkham (CDK) telescopes at both sites, a 0.6 m Ritchie-Chretien telescope at Moore, and a new Nasmyth design 0.7-meter CDK at Mt. Kent instrumented for milli-magnitude precision photometry and wide field imaging, with spectrographs under development. We will describe the operational and data acquisition software, recent research results, and how remote access is being made available to students and observers.

Evolving electrical SCLM models of the Australian continent - results of the South Australia AusLAMP deployment

NASA Astrophysics Data System (ADS)

Robertson, K. E.; Thiel, S.; Heinson, G. S.

2017-12-01

The Australian Lithospheric Architecture Magnetotelluric Project (AusLAMP) is an Australian initiative to map the Australian continental lithosphere using magnetotelluric (MT) stations to obtain a resistivity model of the subsurface. It is a joint project between Geoscience Australia, state surveys, and Universities. We present new MT 3D inversion results of the largest coherent array of the AusLAMP MT deployments to date covering two-thirds of South Australia, funded largely by the Geological Survey of South Australia with additional funding by Geoscience Australia and The University of Adelaide. The model extends across the South Australian Gawler Craton, including the Eucla Basin to the west of the craton and the Flinders Ranges and Curnamona Province to the east. The MT array covers parts of the Australian lithosphere, which has been largely unexplored with seismic tomography methods and provide a unique insight into the tectonic evolution of the continent. We incorporate 284 long-period (10s-10,000s) MT stations separated roughly every half degree latitude and longitude across an area spanning 1200 km x 800 km, south of latitude -28.5 degrees and from longitude 129 degrees to 141 degrees. We invert 24 discrete periods of the impedance tenor between 7 s and 13,000 s, and 22 different periods of the tipper data between 7s-8000 s period. The results show a heterogeneous lower crust and mantle lithosphere with a primarily resistive mantle (>1000 Ωm) lithosphere in the central and western part of the Gawler Craton and Eucla Domain. The model shows a generally NS oriented electric LAB offset from deeper cratonic lithosphere in the west to a shallow lithosphere along the eastern margin of the Gawler Craton extending further east towards the Proterozoic and Phanerozoic eastern part of Australia. The lower crust is generally resistive with elongated lower crustal conductivity anomalies, which are associated with major translithospheric shear zones likely existent since the Archean/Proterozoic and coincident with the craton margins of the Gawler Craton. The geometry of the elongated shear zones follows major trends in the gravity field, isotope geochemistry and location of prospective mineral occurrences. Therefore, these zones reflect areas of enhanced fertility and metasomatism of the continental lithosphere.

Interpretation of shallow electrical features from electromagnetic and magnetotelluric surveys at Mount Hood, Oregon

NASA Astrophysics Data System (ADS)

Goldstein, N. E.; Mozley, E.; Wilt, M.

1982-04-01

A magnetotelluric survey, with a reference magnetometer for noise cancellation, was conducted at accessible locations around Mount Hood, Oregon. Thirty-eight tensor magnetotelluric (MT) and remote telluric stations were set up in clusters around the volcano except for the northwest quadrant, a wilderness area. Because of limited access, station locations were restricted to elevations below 1829 m, or no closer than 5 km from the 3424-m summit. On the basis of the MT results, three areas were later investigated in more detail using a large-moment, controlled-source electromagnetic (EM) system developed at Lawrence Berkeley Laboratory and the University of California at Berkeley. One-dimensional interpretations of EM and MT data on the northeast flank of the mountain near the Cloud Cap eruptive center and on the south flank near Timberline Lodge show a similar subsurface resistivity pattern: a resistive surface layer 400-700 m thick, underlain by a conductive layer with variable thickness and resistivity of <20 ohm m. It is speculated that the surface layer consists of volcanics partially saturated with cold meteoric water. The underlying conductive zone is presumed to be volcanics saturated with water heated within the region of the central conduit and, possibly, at the Cloud Cap side vent. This hypothesis is supported by the existence of warm springs at the base of the mountain, most notably Swim Warm Springs on the south flank, and by several geothermal test wells, one of which penetrates the conductor south of Timberline Lodge. The MT data typically gave a shallower depth to the conductive zone than did the EM data. This is attributed, in part, to the error inherent in one-dimensional MT interpretations of geologically or topographically complex areas. On the other hand, MT was better for resolving the thickness of the conductive layer and deeper structure. The MT data show evidence for a moderately conductive north-south structure on the south flank below the Timberline Lodge and for a broad zone of late Tertiary intrusives concealed on the southeast flank.

INTERPRETATION OF SHALLOW ELECTRICAL FEATURES FROM ELECTROMAGNETIC AND MAGNETOTELLURIC SURVEYS AT MOUNT HOOD, OREGON

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilt, M.; Goldstein, N.E.; Mozley, E.

1981-04-01

A magnetotelluric survey, with a reference magnetometer for noise cancellation, was conducted at accessible locations around Mount Hood, Oregon. Thirty-eight tensor magnetotelluric (MT) and remote telluric stations were set up in clusters around the volcano except for the northwest quadrant, a wilderness area. Because of limited access, station locations were restricted to elevations below 1829 m, or no closer than 5 km from the 3424-m summit. On the basis of the MT results, three areas were later investigated in more detail using a large-moment, controlled-source electromagnetic (EM) system developed at Lawrence Berkeley Laboratory and the University of California at Berkeley.more » One-dimensional interpretations of EM and MT data on the northeast flank of the mountain near the Cloud Cap eruptive center and on the south flank near Timberline Lodge show a similar subsurface resistivity pattern: a resistive surface layer 400-700 m thick, underlain by a conductive layer with variable thickness and resistivity of <20 ohm m. It is speculated that the surface layer consists of volcanics partially saturated with cold meteoric water. The underlying conductive zone is presumed to be volcanics saturated with water heated within the region of the central conduit and, possibly, at the Cloud Cap side vent. This hypothesis is supported by the existence of warm springs at the base of the mountain, most notably Swim Warm Springs on the south flank, and by several geothermal test wells, one of which penetrates the conductor south of Timberline Lodge. The MT data typically gave a shallower depth to the conductive zone than did the EM data. This is attributed, in part, to the error inherent in one-dimensional MT interpretations of geologically or topographically complex areas. On the other hand, MT was better for resolving the thickness of the conductive layer and deeper structure. The MT data show evidence for a moderately conductive north-south structure on the south flank below the Timberline Lodge and for a broad zone of late Tertiary intrusives concealed on the southeast flank.« less

Risk-taking, peer-influence and child maltreatment: a neurocognitive investigation.

PubMed

Hoffmann, Ferdinand; Puetz, Vanessa B; Viding, Essi; Sethi, Arjun; Palmer, Amy; McCrory, Eamon J

2018-01-01

Maltreatment is associated with increased risk of a range of psychiatric disorders, many of which are characterized by altered risk-taking propensity. Currently, little is known about the neural correlates of risk-taking in children exposed to maltreatment, nor whether their risk-taking is atypically modulated by peer influence. Seventy-five 10- to 14-year-old children [maltreated (MT) group: N = 41; non-maltreated Group (NMT): N = 34] performed a Balloon Analogue Risk Task (BART), under three different peer influence conditions: while alone, while being observed by a peer and while being encouraged by a peer to take risks. The MT group engaged in less risk-taking irrespective of peer influence. There was no differential effect of peer influence on risk-taking behaviour across groups. At the neural level, the right anterior insula (rAI) exhibited altered risk sensitivity across conditions in the MT group. Across groups and conditions, rAI risk sensitivity was negatively associated with risk-taking and within the MT group greater rAI risk sensitivity was related to more anxiety symptoms. These findings suggest that children with a history of maltreatment show reduced risk-taking but typical responses to peer influence. Abnormal rAI functioning contributes to the pattern of reduced risk-taking and may predispose children exposed to maltreatment to develop future psychopathology. © The Author (2017). Published by Oxford University Press.

Local and Global Correlations between Neurons in the Middle Temporal Area of Primate Visual Cortex.

PubMed

Solomon, Selina S; Chen, Spencer C; Morley, John W; Solomon, Samuel G

2015-09-01

In humans and other primates, the analysis of visual motion includes populations of neurons in the middle-temporal (MT) area of visual cortex. Motion analysis will be constrained by the structure of neural correlations in these populations. Here, we use multi-electrode arrays to measure correlations in anesthetized marmoset, a New World monkey where area MT lies exposed on the cortical surface. We measured correlations in the spike count between pairs of neurons and within populations of neurons, for moving dot fields and moving gratings. Correlations were weaker in area MT than in area V1. The magnitude of correlations in area MT diminished with distance between receptive fields, and difference in preferred direction. Correlations during presentation of moving gratings were stronger than those during presentation of moving dot fields, extended further across cortex, and were less dependent on the functional properties of neurons. Analysis of the timescales of correlation suggests presence of 2 mechanisms. A local mechanism, associated with near-synchronous spiking activity, is strongest in nearby neurons with similar direction preference and is independent of visual stimulus. A global mechanism, operating over larger spatial scales and longer timescales, is independent of direction preference and is modulated by the type of visual stimulus presented. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The effects of milk thistle on hepatic fibrosis due to methotrexate in rat.

PubMed

Ghaffari, Ali Reza; Noshad, Hamid; Ostadi, Ali; Ghojazadeh, Morteza; Asadi, Parviz

2011-06-01

Extracts of milk thistle (MT), Silybum marianum, have been used as medical remedies since the time of ancient Greece. Methotrexate is a potentially hepatotxic drug. To clarify the hepatoprotective effects of MT on methotrexate. From January 2010 to April 2010, 30 male rats were recruited into three 10-rat subgroups in Tabriz University of Medical Sciences. Normal saline was injected intraperitoneally in the first group (A; the controls); intraperitoneal methotrexate plus oral MT extract were administered to the second group (B) and intraperitoneal methotrexate alone was given to the third group (C). Pre- and post-interventional measuring of serum parameters were carried out every 15 days. After six weeks, the rats were decapitated and histopathological evaluation of liver was done. Serum liver enzymes (AST, ALT), alkaline phosphatase, total and direct bilirubin, creatinine and BUN were measured on days 0, 15, 30, 45. They were significantly higher in the group C, comparing with other two groups. Serum albumin was the least in group C animals as well. There were no significant differences between groups A and B. The mean±SD fibrosis score using semi-quantitative scoring system (SSS) was 1.25±0.46, 1.40±0.52 and 6.70±0.82, in groups A, B and C, respectively (p<0.001). MT extract can effectively prevent methotrexate-induced liver dysfunction and fibrosis in rats.

Prevalence of acute mountain sickness on Mount Fuji: A pilot study.

PubMed

Horiuchi, Masahiro; Endo, Junko; Akatsuka, Shin; Uno, Tadashi; Jones, Thomas E

2016-04-01

Few studies have investigated climbing-related acute mountain sickness (AMS) on Mt Fuji. Although several studies of AMS have been conducted elsewhere, Mt Fuji is unique because there are many mountain lodges between the fifth station (a common starting point for climbers at an altitude of 2305 m) and the summit (3776 m), and many climbers commonly sleep overnight at mountain lodges during their ascents. This study surveyed the prevalence of AMS among climbers on Mt Fuji to determine which factors, if any, were related to the risk of developing AMS. This study collected data from 345 participants who climbed Mt Fuji in August 2013, including information regarding age, sex, climbing experience and whether the climber stayed at a mountain lodge (n = 239). AMS was surveyed using the Lake Louise Score (LLS) questionnaire. The item on perceived sleep quality was excluded for those who did not stay at a mountain lodge (n = 106). The overall prevalence of AMS was 29.5% (≥ 3 LLS with headache). According to a univariate analysis, AMS was not associated with sex (male vs female), age group (20-29, 30-39, 40-49 or >50 years) or stay at a mountain lodge (single day vs overnight stay). Conversely, prior experience climbing Mt Fuji (no prior attempts vs one or more prior attempts) was related to the risk of AMS. In addition, there was a significant deviation in the number of participants reporting poor sleep, and total sleep time was significantly shorter in participants with AMS. These preliminary findings suggest that no single factor can explain the risk for developing AMS while climbing Mt Fuji. In addition, impaired perceived sleep quality was associated with the severity of AMS in climbers who stayed overnight at a mountain lodge. © International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.

Abnormal brain aging as a radical-related disease: A new target for nuclear medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujibayashi, Y.; Yamamoto, S.; Waki, A.

DNA damages caused by endogenously produced radicals are closely correlated with aging. Among them, mitochondrial DNA (mtDNA) deletions have been reported as a memory of DNA damage by oxygen radicals. In fact, clinical as well as experimental studies indicated the accumulation of deleted mtDNA in the brain, myocardium and son on, in aged subjects. In our previous work, radioiodinated radical trapping agent, p-iodophenyl-N-t-butylnitrone, and hypoxia imaging agent, Cu-62 diacetyl-bis-N-4-methyl-thiosemicarbazone have been developed for the diagnosis of radical-related diseases, such as ischemic, inflammation, cancer or aging. The aim of the present work was to evaluate these agents for brain aging studies.more » In our university, an unique animal model, a senescence accelerated model mouse (SAM), has been established. Among the various substrains, SAMP8 showing memory deterioration in its young age ({approximately}3 month) was basically evaluated as an abnormal brain aging model with mtDNA deletion. As controls, SAMR1 showing normal aging and ddY mice were used. MtDNA deletion n the brain was analyzed with polymerase-chain reaction (PCR) method, and relationship between mtDNA deletion and brain uptake of IPBN or Cu-62-ATSM was studied. In 1-3 month old SAMP8 brain, multiple mtDNa deletions were already found and their content was significantly higher than that of SAMR1 or age-matched ddY control. Thus, it was cleared that SAMP8 brain has high tendency to be attacked by endogenously produced oxygen radicals, possibly from its birth. Both IPBN and Cu-ATSM showed significantly higher accumulation in the SAMP8 brain than in the SAMR1 brain, indicating that these agents have high possibility for the early detection of abnormal brain aging as a radical-related disease.« less

University of Hawaii Lure Observatory. [lunar laser ranging system construction

NASA Technical Reports Server (NTRS)

Carter, W. E.; Williams, J. D.

1973-01-01

The University of Hawaii's Institute for Astronomy is currently constructing a lunar laser ranging observatory at the 3050-meter summit of Mt. Haleakala, Hawaii. The Nd YAG laser system to be employed provides three pulses per second, each pulse being approximately 200 picoseconds in duration. The energy contained in one pulse at 5320 A lies in the range from 250 to 350 millijoules. Details of observatory construction are provided together with transmitter design data and information concerning the lunastat, the feed telescope, the relative pointing system, the receiver, and the event timer system.

Growing a Circle of Courage Culture: One School's Journey

ERIC Educational Resources Information Center

Espiner, Deborah; Guild, Diane

2010-01-01

Mt. Richmond Special School is the first Circle of Courage school in New Zealand. The school reflects the richness of the cultural and learning diversity found in many New Zealand schools. Located in the heart of South Auckland, the school's 130 students represent a wide range of ethnic backgrounds. The universal values in the Circle of Courage…

Oocyte mitochondrial deletions and heteroplasmy in a bovine model of ageing and ovarian stimulation.

PubMed

Hammond, Elizabeth R; Green, Mark P; Shelling, Andrew N; Berg, Martin C; Peek, John C; Cree, Lynsey M

2016-04-01

Maternal ageing and ovarian stimulation result in the accumulation of mitochondrial DNA (mtDNA) deletions and heteroplasmy in individual oocytes from a novel bovine model for human assisted reproductive technology (ART). The levels of mtDNA deletions detected in oocytes increased with ovarian ageing. Low levels of mtDNA heteroplasmy were apparent across oocytes and no relationship was identified with respect to ovarian ageing or ovarian stimulation. Oocyte quality decreases with ovarian ageing and it is postulated that the mtDNA may have a role in this decline. The impact of ovarian stimulation on oocyte quality is poorly understood. Human studies investigating these effects are often limited by the use of low quality oocytes and embryos, variation in age and ovarian stimulation regimens within the patients studied, as well as genetic and environmental variability. Further, no study has investigated mtDNA heteroplasmy in individual oocytes using next-generation sequencing (NGS), and little is known about whether the oocyte accumulates heteroplasmic mtDNA mutations following ageing or ovarian stimulation. A novel bovine model for the effect of stimulation and age in human ART was undertaken using cows generated by somatic cell nuclear transfer (SCNT) from one founder, to produce a homogeneous population with reduced genetic and environmental variability. Oocytes and somatic tissues were collected from young (3 years of age; n = 4 females) and old (10 years of age; n = 5 females) cow clones following multiple natural ovarian cycles, as well as oocytes following multiple mild (FSH only) and standard (based on human a long GnRH agonist protocol) ovarian stimulation cycles. In addition, oocytes were recovered in a natural cycle from naturally conceived cows aged 4-13.5 years (n = 10) to provide a heterogeneous cohort for mtDNA deletion studies. The presence or absence of mtDNA deletions were investigated using long-range PCR in individual oocytes (n = 62). To determine the detection threshold for mtDNA heteroplasmy levels in individual oocytes, a novel NGS methodology was validated; artificial mixtures of the Bos taurus and Bos indicus mitochondrial genome were generated at 1, 2, 5, 15 and 50% ratios to experimentally mimic different levels of heteroplasmy. This NGS methodology was then employed to determine mtDNA heteroplasmy levels in single oocytes (n = 24). Oocyte mtDNA deletion and heteroplasmy data were analysed by binary logistic regression with respect to the effects of ovarian ageing and ovarian stimulation regimens. Ovarian ageing, but not ovarian stimulation, increased the number of oocytes exhibiting mtDNA deletions (P = 0.04). A minimum mtDNA heteroplasmy level of 2% was validated as a sensitive (97-100%) threshold for variant detection in individual oocytes using NGS. Few mtDNA heteroplasmies were detected across the individual oocytes, with only 15 oocyte-specific variants confined to two of the 24 oocytes studied. There was no relationship (P > 0.05) evident between ovarian ageing or ovarian stimulation and the presence of mtDNA heteroplasmies. The low number of oocytes collected from the natural ovarian cycles limited the analysis. Fertilization and developmental potential of the oocytes was not assessed as the oocytes were destroyed for mtDNA deletion and heteroplasmy analysis. If the findings of this model apply to the human, this study suggests that the incidence of mtDNA deletions increases with age, but not with degree of ovarian stimulation, while the frequency of mtDNA heteroplasmies may be low regardless of ovarian ageing or level of ovarian stimulation. Funding was provided by Fertility Associates, the Nurture Foundation for Reproductive Research, the Fertility Society of Australia, and the Auckland Medical Research Foundation. J.C.P. is a shareholder of Fertility Associates and M.P.G. received a fellowship from Fertility Associates. The other authors of this manuscript declare no conflict of interest that could be perceived as prejudicing the impartiality of the reported research. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Transient changes in shallow groundwater chemistry during the MSU ZERT CO2 injection experiment

USGS Publications Warehouse

Apps, J.A.; Zheng, Lingyun; Spycher, N.; Birkholzer, J.T.; Kharaka, Y.; Thordsen, J.; Kakouros, E.; Trautz, R.

2011-01-01

Food-grade CO2 was injected into a shallow aquifer through a perforated pipe placed horizontally 1-2 m below the water table at the Montana State University Zero Emission Research and Technology (MSU-ZERT) field site at Bozeman, Montana. The possible impact of elevated CO2 levels on groundwater quality was investigated by analyzing 80 water samples taken before, during, and following CO2 injection. Field determinations and laboratory analyses showed rapid and systematic changes in pH, alkalinity, and conductance, as well as increases in the aqueous concentrations of trace element species. The geochemical data were first evaluated using principal component analysis (PCA) in order to identify correlations between aqueous species. The PCA findings were then used in formulating a geochemical model to simulate the processes likely to be responsible for the observed increases in the concentrations of dissolved constituents. Modeling was conducted taking into account aqueous and surface complexation, cation exchange, and mineral precipitation and dissolution. Reasonable matches between measured data and model results suggest that: (1) CO2 dissolution in the groundwater causes calcite to dissolve. (2) Observed increases in the concentration of dissolved trace metals result likely from Ca+2-driven ion exchange with clays (smectites) and sorption/desorption reactions likely involving Fe (hydr)oxides. (3) Bicarbonate from CO2 dissolution appears to compete for sorption with anionic species such as HAsO4-2, potentially increasing dissolved As levels in groundwater. ?? 2011 Published by Elsevier Ltd.

The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO

PubMed Central

Fratter, C.; Gorman, G.S.; Stewart, J.D.; Buddles, M.; Smith, C.; Evans, J.; Seller, A.; Poulton, J.; Roberts, M.; Hanna, M.G.; Rahman, S.; Omer, S.E.; Klopstock, T.; Schoser, B.; Kornblum, C.; Czermin, B.; Lecky, B.; Blakely, E.L.; Craig, K.; Chinnery, P.F.; Turnbull, D.M.; Horvath, R.; Taylor, R.W.

2010-01-01

Background: Mutations in the Twinkle (PEO1) gene are a recognized cause of autosomal dominant progressive external ophthalmoplegia (adPEO), resulting in the accumulation of multiple mitochondrial DNA (mtDNA) deletions and cytochrome c oxidase (COX)-deficient fibers in skeletal muscle secondary to a disorder of mtDNA maintenance. Patients typically present with isolated extraocular muscle involvement, with little apparent evidence of the clinical heterogeneity documented in other mtDNA maintenance disorders, in particular POLG-related disease. Methods: We reviewed the clinical, histochemical, and molecular genetics analysis of 33 unreported patients from 26 families together with all previous cases described in the literature to define the clinical phenotype associated with PEO1 mutations. Results: Ptosis and ophthalmoparesis were almost universal clinical features among this cohort, with 52% (17/33) reporting fatigue and 33% (11/33) having mild proximal myopathy. Features consistent with CNS involvement were rarely described; however, in 24% (8/33) of the patients, cardiac abnormalities were reported. Mitochondrial histochemical changes observed in muscle showed remarkable variability, as did the secondary mtDNA deletions, which in some patients were only detected by PCR-based assays and not Southern blotting. Moreover, we report 7 novel PEO1 variants. Conclusions: Our data suggest a shared clinical phenotype with variable mild multiorgan involvement, and that the contribution of PEO1 mutations as a cause of adPEO may well be underestimated. Direct sequencing of the PEO1 gene should be considered in adPEO patients prior to muscle biopsy. GLOSSARY adPEO = autosomal dominant progressive external ophthalmoplegia; COX = cytochrome c oxidase; IOSCA = infantile-onset spinocerebellar ataxia; mtDNA = mitochondrial DNA; PEO = progressive external ophthalmoplegia; SANDO = sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; SDH = succinate dehydrogenase. PMID:20479361

Brown and polar bear Y chromosomes reveal extensive male-biased gene flow within brother lineages.

PubMed

Bidon, Tobias; Janke, Axel; Fain, Steven R; Eiken, Hans Geir; Hagen, Snorre B; Saarma, Urmas; Hallström, Björn M; Lecomte, Nicolas; Hailer, Frank

2014-06-01

Brown and polar bears have become prominent examples in phylogeography, but previous phylogeographic studies relied largely on maternally inherited mitochondrial DNA (mtDNA) or were geographically restricted. The male-specific Y chromosome, a natural counterpart to mtDNA, has remained underexplored. Although this paternally inherited chromosome is indispensable for comprehensive analyses of phylogeographic patterns, technical difficulties and low variability have hampered its application in most mammals. We developed 13 novel Y-chromosomal sequence and microsatellite markers from the polar bear genome and screened these in a broad geographic sample of 130 brown and polar bears. We also analyzed a 390-kb-long Y-chromosomal scaffold using sequencing data from published male ursine genomes. Y chromosome evidence support the emerging understanding that brown and polar bears started to diverge no later than the Middle Pleistocene. Contrary to mtDNA patterns, we found 1) brown and polar bears to be reciprocally monophyletic sister (or rather brother) lineages, without signals of introgression, 2) male-biased gene flow across continents and on phylogeographic time scales, and 3) male dispersal that links the Alaskan ABC islands population to mainland brown bears. Due to female philopatry, mtDNA provides a highly structured estimate of population differentiation, while male-biased gene flow is a homogenizing force for nuclear genetic variation. Our findings highlight the importance of analyzing both maternally and paternally inherited loci for a comprehensive view of phylogeographic history, and that mtDNA-based phylogeographic studies of many mammals should be reevaluated. Recent advances in sequencing technology render the analysis of Y-chromosomal variation feasible, even in nonmodel organisms. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Using PubMed search strings for efficient retrieval of manual therapy research literature.

PubMed

Pillastrini, Paolo; Vanti, Carla; Curti, Stefania; Mattioli, Stefano; Ferrari, Silvano; Violante, Francesco Saverio; Guccione, Andrew

2015-02-01

The aim of this study was to construct PubMed search strings that could efficiently retrieve studies on manual therapy (MT), especially for time-constrained clinicians. Our experts chose 11 Medical Subject Heading terms describing MT along with 84 additional potential terms. For each term that was able to retrieve more than 100 abstracts, we systematically extracted a sample of abstracts from which we estimated the proportion of studies potentially relevant to MT. We then constructed 2 search strings: 1 narrow (threshold of pertinent articles ≥40%) and 1 expanded (including all terms for which a proportion had been calculated). We tested these search strings against articles on 2 conditions relevant to MT (thoracic and temporomandibular pain). We calculated the number of abstracts needed to read (NNR) to identify 1 potentially pertinent article in the context of these conditions. Finally, we evaluated the efficiency of the proposed PubMed search strings to identify relevant articles included in a systematic review on spinal manipulative therapy for chronic low back pain. Fifty-five search terms were able to extract more than 100 citations. The NNR to find 1 potentially pertinent article using the narrow string was 1.2 for thoracic pain and 1.3 for temporomandibular pain, and the NNR for the expanded string was 1.9 and 1.6, respectively. The narrow search strategy retrieved all the randomized controlled trials included in the systematic review selected for comparison. The proposed PubMed search strings may help health care professionals locate potentially pertinent articles and review a large number of MT studies efficiently to better implement evidence-based practice. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

From Mount Sinai to Mount Scopus: differences in the role and value of fine needle aspiration for evaluating thyroid nodules.

PubMed

Mazeh, Haggi; Greenstein, Alexander; Swedish, Kristin; Arora, Shalini; Hermon, Hila; Ariel, Ilana; Divino, Celia; Freund, Herbert R; Weber, Kaare

2009-05-01

Fine needle aspiration is the main diagnostic tool used to assess thyroid nodules. To correlate FNA cytology results with surgical pathological findings in two teaching medical centers across the Atlantic. We retrospectively identified 484 patients at Hadassah Hebrew University Medical Center, Jerusalem and Mount Sinai Hospital, New York, by means of both preoperative FNA cytology and a final histopathological report. Results compared FNA diagnosis, histological findings and frozen section results (Mt. Sinai only). The sensitivity value of FNA at Hadassah was 83.0% compared with 79.1% at Mt. Sinai (NS). Specificity values were 86.6 vs. 98.5% (P < 0.05), negative predictive value 78.7 vs. 77.6% (NS) and positive predictive value 89.7 vs. 98.6% (P < 0.05), respectively. "Follicular lesion" was diagnosed on FNA in 33.1% of the patients at Hadassah and in 21.5% at Mt Sinai (P < 0.005) with a malignancy rate of 42.5 vs. 23.1% (P < 0.05), respectively. Frozen section was used in 190 patients at Mt. Sinai (78.5%) with sensitivity and specificity values of 72.3% and 100%. Frozen section results altered the planned operative course in only 6 patients (2.5%). Follicular carcinoma was diagnosed in 12 patients at Hadassah vs. 2 patients at Mt. Sinai (P < 0.05). The sensitivity of FNA at the two institutions was comparable. While malignancy on frozen section is highly specific, it should be used selectively for suspicious FNA results. Follicular lesions and the rate of malignancy in such lesions were more common at Hadassah, favoring a more aggressive surgical approach.

Hexavalent chromium-induced differential disruption of cortical microtubules in some Fabaceae species is correlated with acetylation of α-tubulin.

PubMed

Eleftheriou, Eleftherios P; Adamakis, Ioannis-Dimosthenis S; Michalopoulou, Vasiliki A

2016-03-01

The effects of hexavalent chromium [Cr(VI)] on the cortical microtubules (MTs) of five species of the Fabaceae family (Vicia faba, Pisum sativum, Vigna sinensis, Vigna angularis, and Medicago sativa) were investigated by confocal laser scanning microscopy after immunolocalization of total tubulin with conventional immunofluorescence techniques and of acetylated α-tubulin with the specific 6-11B-1 monoclonal antibody. Moreover, total α-tubulin and acetylated α-tubulin were quantified by Western immunoblotting and scanning densitometry. Results showed the universality of Cr(VI) detrimental effects to cortical MTs, which proved to be a sensitive and reliable subcellular marker for monitoring Cr(VI) toxicity in plant cells. However, a species-specific response was recorded, and a correlation of MT disturbance with the acetylation status of α-tubulin was demonstrated. In V. faba, MTs were depolymerized at the gain of cytoplasmic tubulin background and displayed low α-tubulin acetylation, while in P. sativum, V. sinensis, V. angularis, and M. sativa, MTs became bundled and changed orientation from perpendicular to oblique or longitudinal. Bundled MTs were highly acetylated as determined by both immunofluorescence and Western immunoblotting. Tubulin acetylation in P. sativum and M. sativa preceded MT bundling; in V. sinensis it followed MT derangement, while in V. angularis the two phenomena coincided. Total α-tubulin remained constant in all treatments. Should acetylation be an indicator of MT stabilization, it is deduced that bundled MTs became stabilized, lost their dynamic properties, and were rendered inactive. Results of this report allow the conclusion that Cr(VI) toxicity disrupts MTs and deranges the MT-mediated functions either by depolymerizing or stabilizing them.

Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome.

PubMed

Siegmund, Stephanie E; Yang, Hua; Sharma, Rohit; Javors, Martin; Skinner, Owen; Mootha, Vamsi; Hirano, Michio; Schon, Eric A

2017-12-01

Mitochondrial disorders affecting oxidative phosphorylation (OxPhos) are caused by mutations in both the nuclear and mitochondrial genomes. One promising candidate for treatment is the drug rapamycin, which has been shown to extend lifespan in multiple animal models, and which was previously shown to ameliorate mitochondrial disease in a knock-out mouse model lacking a nuclear-encoded gene specifying an OxPhos structural subunit (Ndufs4). In that model, relatively high-dose intraperitoneal rapamycin extended lifespan and improved markers of neurological disease, via an unknown mechanism. Here, we administered low-dose oral rapamycin to a knock-in (KI) mouse model of authentic mtDNA disease, specifically, progressive mtDNA depletion syndrome, resulting from a mutation in the mitochondrial nucleotide salvage enzyme thymidine kinase 2 (TK2). Importantly, low-dose oral rapamycin was sufficient to extend Tk2KI/KI mouse lifespan significantly, and did so in the absence of detectable improvements in mitochondrial dysfunction. We found no evidence that rapamycin increased survival by acting through canonical pathways, including mitochondrial autophagy. However, transcriptomics and metabolomics analyses uncovered systemic metabolic changes pointing to a potential 'rapamycin metabolic signature.' These changes also implied that rapamycin may have enabled the Tk2KI/KI mice to utilize alternative energy reserves, and possibly triggered indirect signaling events that modified mortality through developmental reprogramming. From a therapeutic standpoint, our results support the possibility that low-dose rapamycin, while not targeting the underlying mtDNA defect, could represent a crucial therapy for the treatment of mtDNA-driven, and some nuclear DNA-driven, mitochondrial diseases. © The Author 2017. Published by Oxford University Press.

[Dr. Michiharu Matsuoka, founder of the Department of Orthopaedic Surgery, Kyoto University, and his achievements. Part 4: Prof. M. Matsuoka's lecture to medical and civic communities].

PubMed

Hirotani, Hayato

2010-03-01

Dr. M. Matsuoka gave many lectures to physicians at the Postdoctoral Course Lectures sponsored by the Kyoto Eisei Kensasho (Kyoto Bacterial and Biochemical Laboratory) run by the Kyoto Medical Association, and the Postdoctoral Course Lectures of the Kyoto Medical School, Kyoto Imperial University. He was also invited to give lectures at several regional medical associations. He also was a speaker at the Kyoto Imperial University Extension course and he lectured at the Enryakuji Temple on Mt. Hiei, sponsored by a newspaper company. It is remarkable that these activities were carried out in addition to his other notable academic work previously reported.

Muon g -2 and dark matter suggest nonuniversal gaugino masses: S U (5 )×A4 case study at the LHC

NASA Astrophysics Data System (ADS)

Belyaev, Alexander S.; King, Steve F.; Schaefers, Patrick B.

2018-06-01

We argue that in order to account for the muon anomalous magnetic moment g -2 , dark matter and LHC data, nonuniversal gaugino masses Mi at the high scale are required in the framework of the minimal supersymmetric standard model. We also need a right-handed smuon μ˜R with a mass around 100 GeV, evading LHC searches due to the proximity of a neutralino χ˜10 several GeV lighter which allows successful dark matter. We discuss such a scenario in the framework of an S U (5 ) grand unified theory (GUT) combined with A4 family symmetry, where the three 5 ¯ representations form a single triplet of A4 with a unified soft mass mF, while the three 10 representations are singlets of A4 with independent soft masses mT 1,mT 2,mT 3. Although mT 2 (and hence μ˜R) may be light, the muon g -2 and relic density also requires light M1≃250 GeV , which is incompatible with universal gaugino masses due to LHC constraints on M2 and M3 arising from gaugino searches. After showing that universal gaugino masses M1 /2 at the GUT scale are excluded by gluino searches, we provide a series of benchmarks which show that while M1=M2≪M3 is in tension with 8 and 13 TeV LHC data, M1

An Undergraduate Summer Research Program Through A University-Community College Partnership: Design and Results

NASA Astrophysics Data System (ADS)

Hood, Carol E.; Hood, Michael; Woodney, Laura

2016-06-01

We present a model for an undergraduate summer research program in astronomy targeted at 2-year and 4-year students and the short-term success of student participants. California State University San Bernardino (CSUSB) is Hispanic Serving Institution (HSI) serving 16,000 students, with no dominant ethnic or racial majority. Most (80%) CSUSB students are first-generation college students, and many of the students - both minority and “majority” - are economically disadvantaged and cannot afford to take on research projects without compensation. Approximately 60 percent of our students transfer from two year colleges, and all of the local community colleges are also officially designated as minority serving institutions. Mt. San Antonio College (Mt. SAC) is the largest single-campus community college in the state of California. It serves a student population of approximately 60,000 students (~35,000 full-time equivalent), also with no dominant ethnic or racial majority. Mt. SAC is currently 5th in the state in transfer ranking into the CSU system.In an effort to involve students in research as early as possible, we selected 2 students from each campus to participate in a summer research program. This program taught students observational techniques, data reduction and analysis skills, and then allowed them to work on more complex faculty astronomical research projects. These students were not selected based on their grades, or specific courses completed, simply based on their essays expressing their interests in astronomy. Students were only required to have already completed at least 1 physics or astronomy class and typically would be classified as freshman or sophomores. This program ran for 2 summers, before funding ran out. By the end of each summer, students were able to run the state-of-the-art campus observatory, and many chose to continue working on their research projects into the school year. To date, 3 students were selected for further summer research programs at SETI, CIERA, UC-Irvine, and NASA centers JPL and Armstrong. An additional 3 students have obtained employment directly or indirectly related to the skills they developed in the program and 2 of the Mt. SAC students have transferred to 4-year institutions.

75 FR 55713 - Air Quality Implementation Plans; Montana; Attainment Plan for Libby, MT PM2.5

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-14

... proposing to find on-road directly emitted PM 2.5 and oxides of nitrogen (NO X ) in the Libby, Montana... contribute to fine particle concentrations: direct PM 2.5 , sulfur dioxide (SO 2 ), nitrogen oxides (NO X... balance study (CMB) was conducted during the winter of 2003-2004 by the University of Montana, Center for...

Loss of the mitochondrial protein-only ribonuclease P complex causes aberrant tRNA processing and lethality in Drosophila.

PubMed

Sen, Aditya; Karasik, Agnes; Shanmuganathan, Aranganathan; Mirkovic, Elena; Koutmos, Markos; Cox, Rachel T

2016-07-27

Proteins encoded by mitochondrial DNA are translated using mitochondrially encoded tRNAs and rRNAs. As with nuclear encoded tRNAs, mitochondrial tRNAs must be processed to become fully functional. The mitochondrial form of ribonuclease P (mt:RNase P) is responsible for 5'-end maturation and is comprised of three proteins; mitochondrial RNase P protein (MRPP) 1 and 2 together with proteinaceous RNase P (PRORP). However, its mechanism and impact on development is not yet known. Using homology searches, we have identified the three proteins composing Drosophila mt:RNase P: Mulder (PRORP), Scully (MRPP2) and Roswell (MRPP1). Here, we show that each protein is essential and localizes with mitochondria. Furthermore, reducing levels of each causes mitochondrial deficits, which appear to be due at least in part to defective mitochondrial tRNA processing. Overexpressing two members of the complex, Mulder and Roswell, is also lethal, and in the case of Mulder, causes abnormal mitochondrial morphology. These data are the first evidence that defective mt:RNase P causes mitochondrial dysfunction, lethality and aberrant mitochondrial tRNA processing in vivo, underscoring its physiological importance. This in vivo mt:RNase P model will advance our understanding of how loss of mitochondrial tRNA processing causes tissue failure, an important aspect of human mitochondrial disease. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

How MESSENGER Meshes Simulations and Games with Citizen Science

NASA Astrophysics Data System (ADS)

Hirshon, B.; Chapman, C. R.; Edmonds, J.; Goldstein, J.; Hallau, K. G.; Solomon, S. C.; Vanhala, H.; Weir, H. M.; Messenger Education; Public Outreach (Epo) Team

2010-12-01

How MESSENGER Meshes Simulations and Games with Citizen Science In the film The Last Starfighter, an alien civilization grooms their future champion—a kid on Earth—using a video game. As he gains proficiency in the game, he masters the skills he needs to pilot a starship and save their civilization. The NASA MESSENGER Education and Public Outreach (EPO) Team is using the same tactic to train citizen scientists to help the Science Team explore the planet Mercury. We are building a new series of games that appear to be designed primarily for fun, but that guide players through a knowledge and skill set that they will need for future science missions in support of MESSENGER mission scientists. As players score points, they gain expertise. Once they achieve a sufficiently high score, they will be invited to become participants in Mercury Zoo, a new program being designed by Zooniverse. Zooniverse created Galaxy Zoo and Moon Zoo, programs that allow interested citizens to participate in the exploration and interpretation of galaxy and lunar data. Scientists use the citizen interpretations to further refine their exploration of the same data, thereby narrowing their focus and saving precious time. Mercury Zoo will be designed with input from the MESSENGER Science Team. This project will not only support the MESSENGER mission, but it will also add to the growing cadre of informed members of the public available to help with other citizen science projects—building on the concept that engaged, informed citizens can help scientists make new discoveries. The MESSENGER EPO Team comprises individuals from the American Association for the Advancement of Science (AAAS); Carnegie Academy for Science Education (CASE); Center for Educational Resources (CERES) at Montana State University (MSU) - Bozeman; National Center for Earth and Space Science Education (NCESSE); Johns Hopkins University Applied Physics Laboratory (JHU/APL); National Air and Space Museum (NASM); Science Systems and Applications, Inc. (SSAI); and Southwest Research Institute (SwRI).

Origins of domestic dog in southern East Asia is supported by analysis of Y-chromosome DNA.

PubMed

Ding, Z-L; Oskarsson, M; Ardalan, A; Angleby, H; Dahlgren, L-G; Tepeli, C; Kirkness, E; Savolainen, P; Zhang, Y-P

2012-05-01

Global mitochondrial DNA (mtDNA) data indicates that the dog originates from domestication of wolf in Asia South of Yangtze River (ASY), with minor genetic contributions from dog-wolf hybridisation elsewhere. Archaeological data and autosomal single nucleotide polymorphism data have instead suggested that dogs originate from Europe and/or South West Asia but, because these datasets lack data from ASY, evidence pointing to ASY may have been overlooked. Analyses of additional markers for global datasets, including ASY, are therefore necessary to test if mtDNA phylogeography reflects the actual dog history and not merely stochastic events or selection. Here, we analyse 14,437 bp of Y-chromosome DNA sequence in 151 dogs sampled worldwide. We found 28 haplotypes distributed in five haplogroups. Two haplogroups were universally shared and included three haplotypes carried by 46% of all dogs, but two other haplogroups were primarily restricted to East Asia. Highest genetic diversity and virtually complete phylogenetic coverage was found within ASY. The 151 dogs were estimated to originate from 13-24 wolf founders, but there was no indication of post-domestication dog-wolf hybridisations. Thus, Y-chromosome and mtDNA data give strikingly similar pictures of dog phylogeography, most importantly that roughly 50% of the gene pools are shared universally but only ASY has nearly the full range of genetic diversity, such that the gene pools in all other regions may derive from ASY. This corroborates that ASY was the principal, and possibly sole region of wolf domestication, that a large number of wolves were domesticated, and that subsequent dog-wolf hybridisation contributed modestly to the dog gene pool.

Origins of domestic dog in Southern East Asia is supported by analysis of Y-chromosome DNA

PubMed Central

Ding, Z-L; Oskarsson, M; Ardalan, A; Angleby, H; Dahlgren, L-G; Tepeli, C; Kirkness, E; Savolainen, P; Zhang, Y-P

2012-01-01

Global mitochondrial DNA (mtDNA) data indicates that the dog originates from domestication of wolf in Asia South of Yangtze River (ASY), with minor genetic contributions from dog–wolf hybridisation elsewhere. Archaeological data and autosomal single nucleotide polymorphism data have instead suggested that dogs originate from Europe and/or South West Asia but, because these datasets lack data from ASY, evidence pointing to ASY may have been overlooked. Analyses of additional markers for global datasets, including ASY, are therefore necessary to test if mtDNA phylogeography reflects the actual dog history and not merely stochastic events or selection. Here, we analyse 14 437 bp of Y-chromosome DNA sequence in 151 dogs sampled worldwide. We found 28 haplotypes distributed in five haplogroups. Two haplogroups were universally shared and included three haplotypes carried by 46% of all dogs, but two other haplogroups were primarily restricted to East Asia. Highest genetic diversity and virtually complete phylogenetic coverage was found within ASY. The 151 dogs were estimated to originate from 13–24 wolf founders, but there was no indication of post-domestication dog–wolf hybridisations. Thus, Y-chromosome and mtDNA data give strikingly similar pictures of dog phylogeography, most importantly that roughly 50% of the gene pools are shared universally but only ASY has nearly the full range of genetic diversity, such that the gene pools in all other regions may derive from ASY. This corroborates that ASY was the principal, and possibly sole region of wolf domestication, that a large number of wolves were domesticated, and that subsequent dog–wolf hybridisation contributed modestly to the dog gene pool. PMID:22108628

The mitochondrial genome of Paraspadella gotoi is highly reduced and reveals that chaetognaths are a sister-group to protostomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helfenbein, Kevin G.; Fourcade, H. Matthew; Vanjani, Rohit G.

2004-05-01

We report the first complete mitochondrial (mt) DNA sequence from a member of the phylum Chaetognatha (arrow worms). The Paraspadella gotoi mtDNA is highly unusual, missing 23 of the genes commonly found in animal mtDNAs, including atp6, which has otherwise been found universally to be present. Its 14 genes are unusually arranged into two groups, one on each strand. One group is punctuated by numerous non-coding intergenic nucleotides, while the other group is tightly packed, having no non-coding nucleotides, leading to speculation that there are two transcription units with differing modes of expression. The phylogenetic position of the Chaetognatha withinmore » the Metazoa has long been uncertain, with conflicting or equivocal results from various morphological analyses and rRNA sequence comparisons. Comparisons here of amino acid sequences from mitochondrially encoded proteins gives a single most parsimonious tree that supports a position of Chaetognatha as sister to the protostomes studied here. From this, one can more clearly interpret the patterns of evolution of various developmental features, especially regarding the embryological fate of the blastopore.« less

31P-Magnetization Transfer Magnetic Resonance Spectroscopy Measurements of In Vivo Metabolism

PubMed Central

Befroy, Douglas E.; Rothman, Douglas L.; Petersen, Kitt Falk; Shulman, Gerald I.

2012-01-01

Magnetic resonance spectroscopy offers a broad range of noninvasive analytical methods for investigating metabolism in vivo. Of these, the magnetization-transfer (MT) techniques permit the estimation of the unidirectional fluxes associated with metabolic exchange reactions. Phosphorus (31P) MT measurements can be used to examine the bioenergetic reactions of the creatine-kinase system and the ATP synthesis/hydrolysis cycle. Observations from our group and others suggest that the inorganic phosphate (Pi) → ATP flux in skeletal muscle may be modulated by certain conditions, including aging, insulin resistance, and diabetes, and may reflect inherent alterations in mitochondrial metabolism. However, such effects on the Pi → ATP flux are not universally observed under conditions in which mitochondrial function, assessed by other techniques, is impaired, and recent articles have raised concerns about the absolute magnitude of the measured reaction rates. As the application of 31P-MT techniques becomes more widespread, this article reviews the methodology and outlines our experience with its implementation in a variety of models in vivo. Also discussed are potential limitations of the technique, complementary methods for assessing oxidative metabolism, and whether the Pi → ATP flux is a viable biomarker of metabolic function in vivo. PMID:23093656

Alignment and phasing of deployable telescopes

NASA Technical Reports Server (NTRS)

Woolf, N. J.; Ulich, B. L.

1983-01-01

The experiences in coaligning and phasing the Multi-Mirror Telescope (MMT), together with studies in setting up radio telescopes, are presented. These experiences are discussed, and on the basis they furnish, schemes are suggested for coaligning and phasing four large future telescopes with complex primary mirror systems. These telescopes are MT2, a 15-m-equivalent MMT, the University of California Ten Meter Telescope, the 10 m sub-mm wave telescope of the University of Arizona and the Max Planck Institute for Radioastronomy, and the Large Deployable Reflector, a future space telescope for far-IR and sub-mm waves.

Metallothionein Isoform Expression in Benign and Malignant Thyroid Lesions.

PubMed

Wojtczak, Beata; Pula, Bartosz; Gomulkiewicz, Agnieszka; Olbromski, Mateusz; Podhorska-Okolow, Marzena; Domoslawski, Paweł; Bolanowski, Marek; Daroszewski, Jacek; Dziegiel, Piotr

2017-09-01

Metallothioneins (MTs) are involved in numerous cell processes such as binding and transport of zinc and copper ions, differentiation, proliferation and apoptosis, therefore contributing to carcinogenesis. Scarce data exist on their expression in benign and malignant lesions of the thyroid. mRNA expression of functional isoforms of MT genes (MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1X, MT2A, MT4) was studied in 17 nodular goiters (NG), 12 follicular adenomas (FA) and 26 papillary thyroid carcinomas (PTC). One-way ANOVA revealed significant differences in mRNA expression levels of MT1A (p<0.05), MT1E (p<0.005), MT1F (p<0.0001), MT1G (p<0.005), MT1X (p<0.0005) and MT2A (p<0.005) in the analyzed samples. Post hoc analysis confirmed a significantly lower expression of MT1A mRNA in PTC compared to NG (p<0.05). Significant down-regulation was also noted for other MT isoforms in PTC in comparison to NG: MT1E (p<0.05), MT1F (p<0.0001), MT1G (p<0.005), MT1X (p<0.0005) and MT2A (p<0.05). In addition, significant down-regulation of MT1F and MT1G in FA compared to NG was observed (p<0.005 and p<0.05, respectively). Expression of functional MT isoforms may contribute to thyroid carcinogenesis and potentially serve as a diagnostic marker in distinguishing benign and malignant lesions. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Physical studies of small asteroids. I - Lightcurves and taxonomy of 10 asteroids

NASA Technical Reports Server (NTRS)

Wisniewski, W. Z.

1991-01-01

Photometric observations of 10 small asteroids (10 km or less in diameter), obtained using the 1.5-m Mt. Lemmon and 2.3-m Kitt Peak telescopes of the University of Arizona during 1986-1987, are reported. The instrumentation and data-reduction techniques employed are described, and the results are presented in tables and light-curve plots and briefly characterized.

Proceedings of the 2011 AFMS Medical Research Symposium. Volume 5. Operational Medicine (In-Garrison Care) Track

DTIC Science & Technology

2012-02-01

Tl’aMfer II’MU iW! Bf" Air’IAAty H.arwlover "• porn nblt Btdfid! Y&bfl RnMt lj!eeCiqs roilive Aid! SitturtiM Backc round(History...50 Prevention of Low Back Pain in the Military (POLM) cluster randomized trial US Army-Baylor University Lt Col John Childs , Associate Professor

Final Report for Contract N00014-89-J-3047 (Yale University)

DTIC Science & Technology

1992-06-30

REPORTING PERIOD: 1 July 1989 - 30 June 1992 QOJCTI: To determine the transmission dynamics of cnidarian allorecognition using standard breeding...These results essentially obviate all prior interpretations of the genetics of cnidarian allorecognition as grossly oversimplified. In addition, the...laboratory has (see references below) (1) reported the first homeoboxes from cnidarians , (2) used mtDNA conformation to demonstrate that Anthozoa are the

Atrazine sorption by hydroxy-interlayered clays and their organic complexes.

PubMed

Indraratne, Srimathie P; Farenhorst, Annemieke; Goh, Tee Boon

2008-01-01

This study examined the sorption of atrazine by hydroxy-Fe interlayered montmorillonite (FeMt) and its hydroquinone (FeMtHQ), citrate (FeMtCt) and catechol (FeMtCC) complexes as well as by hydroxy-Al interlayered montmorillonite (AlMt) and its hydroquinone (AlMtHQ) and citrate (AlMtCt) complexes. Found among the clays were sorption distribution coefficients (K(d)) ranging from 24 to 123 mL g(-1) and maximum sorption (M) ranging from 2.2 to 16.8 microg g(-1). Both K(d) and M decreased in the order of FeMtCC > FeMtHQ > AlMtHQ > (AlMt = FeMt) > (AlMtCt = FeMtCt). The pH was negatively correlated with both K(d) (r = -0.90, p < 0.001) and M (r = -0.81, p < 0.001). When interlayered clays were associated with humified material (FeMtCC, FeMtHQ, AlMtHQ), both K(d) (r > 0.96, p < 0.01) and M (r > 0.94, p < 0.01) were highly positively correlated with total organic C and alkali-soluble C. However, clays with non-humified organic compounds (FeMtCt and AlMtCt) sorbed less atrazine than clays without any organic C (FeMt and AlMt). This suggests that functional groups of Fe-OH and Al-OH in FeMt and AlMt reduced the available sorption sites for atrazine by making complexes with citrate ions while forming FeMtCt and AlMtCt. The atrazine was sorbed through the hydrophobic interactions with organic compound surfaces as well as through H-bonding and ionic bonding with clay-mineral surfaces.

The MtDMI2-MtPUB2 Negative Feedback Loop Plays a Role in Nodulation Homeostasis1[OPEN

PubMed Central

Deng, Jie; Zhu, Fugui; Lu, Zheng

2018-01-01

DOES NOT MAKE INFECTION 2 (MtDMI2) is a Leu rich repeat-type receptor kinase required for signal transduction in the Medicago truncatula/Sinorhizobium meliloti symbiosis pathway. However, the mechanisms through which MtDMI2 participates in nodulation homeostasis are poorly understood. In this study, we identified MtPUB2—a novel plant U-box (PUB)–type E3 ligase—and showed that it interacts with MtDMI2. MtDMI2 and MtPUB2 accumulation were shown to be similar in various tissues. Roots of plants in which MtPUB2 was silenced by RNAi (MtPUB2-RNAi plants) exhibited impaired infection threads, fewer nodules, and shorter primary root lengths compared to those of control plants transformed with empty vector. Using liquid chromatography-tandem mass spectrometry, we showed that MtDMI2 phosphorylates MtPUB2 at Ser-316, Ser-421, and Thr-488 residues. When MtPUB2-RNAi plants were transformed with MtPUB2S421D, which mimics the phosphorylated state, MtDMI2 was persistently ubiquitinated and degraded by MtPUB2S421D, resulting in fewer nodules than observed in MtPUB2/MtPUB2-RNAi-complemented plants. However, MtPUB2S421A/MtPUB2-RNAi-complemented plants showed no MtPUB2 ubiquitination activity, and their nodulation phenotype was similar to that of MtPUB2-RNAi plants transformed with empty vector. Further studies demonstrated that these proteins form a negative feedback loop of the prey (MtDMI2)-predator (MtPUB2) type. Our results suggest that the MtDMI2-MtPUB2 negative feedback loop, which displays crosstalk with the long-distance autoregulation of nodulation via MtNIN, plays an important role in nodulation homeostasis. PMID:29440269

Low Birth Weight: A Descriptive Study of Risk Factors

DTIC Science & Technology

1999-01-07

abruption Dx on admit MT Placenta previa Yes Placenta previa Dx complete/partial MT Smoking Yes Tobacco use this pregnancy MT Heavy alcohol use Yes...Multiple Gestation MT Urinary tract infection MT *Anemia MT Fetal anomalies MT Abruptio placentae MT Placenta previa MT Smoking MT Alcohol use...categories: (a) problems with the placenta , (b) problems with the pregnant woman herself, (c) problems with the fetus itself, or (d) any

Larvicidal effects of mineral turpentine, low aromatic white spirits, aqueous extracts of Cassia alata, and aqueous extracts, ethanolic extracts and essential oil of betel leaf (Piper betle) on Chrysomya megacephala.

PubMed

Kumarasinghe, Sujith Prasad W; Karunaweera, Nadira D; Ihalamulla, Ranjan L; Arambewela, Lakshmi S R; Dissanayake, Roshinie D S C T

2002-12-01

Many methods have been employed, with variable success, in the treatment of cutaneous myiasis caused by Chrysomya species. Experiment 1: to assess the larvicidal effect of mineral turpentine (MT) and the main ingredient of MT, low aromatic white spirits (LAWS), on Chrysomya megacephala larvae in vitro. Experiment 2: to assess the larvicidal effects of aqueous extracts of winged senna (Cassia alata), and aqueous extracts, ethanolic extracts and essential oil of betel leaf (Piper betle). In experiment 1, two samples of LAWS were obtained from two industrialists (samples 1 and 2). Adult flies of C. megacephala were bred in the insectory of the Department of Parasitology, Faculty of Medicine, University of Colombo. Petri dishes were prepared with pads of cotton wool. These cotton pads were soaked separately in MT, LAWS samples 1 and 2, and normal saline as a control. Ten larvae were placed in each Petri dish. The activity of the larvae was observed and recorded half-hourly. MT and the two samples of LAWS were analyzed by chromatography. In experiment 2, volatile essential oil of betel was prepared using a standard steam distillation process. An ethanolic extract of betel was obtained after boiling the crushed leaf with water, and mixing the stock with ethanol. Betel oil dilutions of 1-4% were prepared using 1% Tween 80 (v/v aq) as a solvent, with 0.05 g/100 mL sodium lauryl sulphate (as stabilizer) and 0.01 g/100 mL methyl paraben (as a preservative). Cotton wool swabs soaked in 1, 2, 3 and 4% essential oil of betel in 1% Tween 80 (v/v aq) prepared as above, 1, 2, 3 and 4% ethanolic extract of betel, 50 and 25% aqueous extract of C. alata, and 50 and 25% aqueous extract of betel were placed in separate Petri dishes. Ten larvae were placed in each Petri dish. 1% Tween 80 solvent with the stabilizer and the preservative, but without betel essential oil, was used as a negative control and MT was used as a positive control. Larval motility was assessed as before. MT and the two LAWS samples killed the larvae in vitro within 4 h. Chromatography showed more unidentified constituents in MT than in pure LAWS, indicating additional substances in MT. The 4 and 3% preparations of the essential oil of betel were effective in killing 100% of the larvae of Chrysomya within 3 h 30 min. The 2% extract of betel essential oil killed 96.7% of larvae in 4 h. Ethanolic and aqueous extracts of betel, the aqueous extract of C. alata, normal saline and the Tween 80 solvent were not larvicidal. MT and LAWS, the main ingredient of MT, were effective in killing Chrysomya larvae. Essential oil obtained from betel leaves also showed a dose-dependent larvicidal effect on Chrysomya larvae. This natural product may be effective in the treatment of wound myiasis.

Gender identity rather than sexual orientation impacts on facial preferences.

PubMed

Ciocca, Giacomo; Limoncin, Erika; Cellerino, Alessandro; Fisher, Alessandra D; Gravina, Giovanni Luca; Carosa, Eleonora; Mollaioli, Daniele; Valenzano, Dario R; Mennucci, Andrea; Bandini, Elisa; Di Stasi, Savino M; Maggi, Mario; Lenzi, Andrea; Jannini, Emmanuele A

2014-10-01

Differences in facial preferences between heterosexual men and women are well documented. It is still a matter of debate, however, how variations in sexual identity/sexual orientation may modify the facial preferences. This study aims to investigate the facial preferences of male-to-female (MtF) individuals with gender dysphoria (GD) and the influence of short-term/long-term relationships on facial preference, in comparison with healthy subjects. Eighteen untreated MtF subjects, 30 heterosexual males, 64 heterosexual females, and 42 homosexual males from university students/staff, at gay events, and in Gender Clinics were shown a composite male or female face. The sexual dimorphism of these pictures was stressed or reduced in a continuous fashion through an open-source morphing program with a sequence of 21 pictures of the same face warped from a feminized to a masculinized shape. An open-source morphing program (gtkmorph) based on the X-Morph algorithm. MtF GD subjects and heterosexual females showed the same pattern of preferences: a clear preference for less dimorphic (more feminized) faces for both short- and long-term relationships. Conversely, both heterosexual and homosexual men selected significantly much more dimorphic faces, showing a preference for hyperfeminized and hypermasculinized faces, respectively. These data show that the facial preferences of MtF GD individuals mirror those of the sex congruent with their gender identity. Conversely, heterosexual males trace the facial preferences of homosexual men, indicating that changes in sexual orientation do not substantially affect preference for the most attractive faces. © 2014 International Society for Sexual Medicine.

[Contribution of medical technologists in team medical care of diabetics].

PubMed

Sato, Itsuko; Jikimoto, Takumi; Ooyabu, Chinami; Kusuki, Mari; Okano, Yosie; Mukai, Masahiko; Kawano, Seiji; Kumagai, Shunichi

2006-08-01

For the effective treatment of diabetic mellitus (DM), patients are encouraged to self-manage their disease according to the doctor's instructions and advice from certified diabetes educators (CDE) and other comedical staff. Therefore, the cooperation of medical staff consisting of a doctor, CDE, nurse, pharmacist, dietitian, and medical technologist is important for DM education. Medical technologists licensed for CDE (MT-CDE) have been participating in the DM education team in Kobe University Hospital since 2000. MT-CDE are in charge of classes for medical tests, guidance for self-monitoring of blood glucose and teaching how to read the fluctuation graph of the blood glucose level in the education program for hospitalized DM patients. MT-CDEs teach at the bedside how to read the results of medical tests during the first few days of hospitalization using pamphlets for medical tests. The pamphlets are made comprehensible for patients by using graphics and photographs as much as possible. It is important to create a friendly atmosphere and answer frank questions from patients, since they often feel stress when having medical tests at the early stage of hospitalization. This process of questions and answers promotes their understanding of medical tests, and seems to reduce their anxiety about having tests. We repeatedly evaluate their level of understanding during hospitalization. By showing them the fluctuation graph of the glucose level, patients can easily understand the status of their DM. When prescriptions are written on the graph, their therapeutic effects are more comprehensible for the patients. The items written on the graph are chosen to meet the level of understanding of each patient to promote their motivation. In summary, the introduction of MT-CDE has been successful in the education program for DM patients in our hospital. We plan to utilize the skills and knowledge of MT-CDE more in our program so that our DM education program will help patients cope with life with DM.

Muscle metabolism, temperature, and function during prolonged, intermittent, high-intensity running in air temperatures of 33 degrees and 17 degrees C.

PubMed

Morris, J G; Nevill, M E; Boobis, L H; Macdonald, I A; Williams, C

2005-12-01

Nine unacclimatized university sportsmen performed a prolonged, intermittent, high-intensity shuttle running test in hot (HT) (33 degrees C, dry bulb temperature, approximately 28 %, relative humidity) and moderate (MT) (17 degrees C, 63 %) environmental conditions. Subjects performed 60 m of walking, a 15-m sprint, 60 m of cruising ( approximately 85 % V.O (2max)), and 60 m of jogging ( approximately 45 %V.O (2max)) for 14.8 +/- 0.1 min followed by a 3-min rest, repeated until volitional exhaustion. The hot trial was performed first followed, 14 days later, by the moderate trial. During exercise subjects drank water ad libitum. Subjects ran almost twice as far in the moderate as in the hot trial (HT 11216 +/- 1411, MT 21644 +/- 1629, m, p < 0.01), and the decline in average 15-m sprint performance was greater in the heat (HT, 0.17 +/- 0.05, MT, 0.09 +/- 0.03, s, p < 0.05). Average heart rates, blood lactate and glucose, and plasma adrenaline and noradrenaline concentrations were greater in the HT (main effect trial, p < 0.01), as were serum cortisol concentration (main effect trial p < 0.05, n = 5) and muscle temperature (HT exhaustion vs. same time point in MT, 40.2 +/- 0.3 vs. 39.3 +/- 0.2, degrees C, p < 0.01). Peak torque during knee flexion and extension was not different pre-and post-exercise in the HT. Muscle glycogen utilization tended to be greater in the heat (HT 193.2 +/- 19.5, MT 143.8 +/- 23.9, mmol . kg dry wt (-1), p = 0.055, n = 8). In 7 out of the 8 subjects the increase in utilization was between 19 and just over 200 % greater in the HT. Glycogen remaining in the muscle at exhaustion was greater in the hot than moderate trial (HT 207.4 +/- 34.3, MT 126.5 +/- 46.8, mmol . kg dry wt (-1), p < 0.01, n = 8). Rectal temperature (T (rec)) was higher in the HT at exhaustion than at the same point in time in the moderate trial (HT, 39.60 +/- 0.15 vs. MT 38.75 +/- 0.10, degrees C, interaction trial-time, p < 0.01). There was a very strong negative relationship between rate of rise in T (rec) and distance completed in the HT (HT r = - 0.90, p < 0.01, MT r = - 0.76, p < 0.05). Thus, the earlier onset of exhaustion during prolonged intermittent shuttle running in the heat is associated with hyperthermia. However, while muscle glycogen utilization may be elevated by heat stress, low whole muscle glycogen concentrations would not seem to be the cause of this earlier exhaustion.

The Dostoevsky Machine in Georgetown: scientific translation in the Cold War.

PubMed

Gordin, Michael D

2016-04-01

Machine Translation (MT) is now ubiquitous in discussions of translation. The roots of this phenomenon - first publicly unveiled in the so-called 'Georgetown-IBM Experiment' on 9 January 1954 - displayed not only the technological utopianism still associated with dreams of a universal computer translator, but was deeply enmeshed in the political pressures of the Cold War and a dominating conception of scientific writing as both the goal of machine translation as well as its method. Machine translation was created, in part, as a solution to a perceived crisis sparked by the massive expansion of Soviet science. Scientific prose was also perceived as linguistically simpler, and so served as the model for how to turn a language into a series of algorithms. This paper follows the rise of the Georgetown program - the largest single program in the world - from 1954 to the (as it turns out, temporary) collapse of MT in 1964.

A Receptor-Like Kinase, Related to Cell Wall Sensor of Higher Plants, is Required for Sexual Reproduction in the Unicellular Charophycean Alga, Closterium peracerosum-strigosum-littorale Complex.

PubMed

Hirano, Naoko; Marukawa, Yuka; Abe, Jun; Hashiba, Sayuri; Ichikawa, Machiko; Tanabe, Yoichi; Ito, Motomi; Nishii, Ichiro; Tsuchikane, Yuki; Sekimoto, Hiroyuki

2015-07-01

Here, we cloned the CpRLK1 gene, which encodes a receptor-like protein kinase expressed during sexual reproduction, from the heterothallic Closterium peracerosum-strigosum-littorale complex, one of the closest unicellular alga to land plants. Mating-type plus (mt(+)) cells with knockdown of CpRLK1 showed reduced competence for sexual reproduction and formed an abnormally enlarged conjugation papilla after pairing with mt(-) cells. The knockdown cells were unable to release a naked gamete, which is indispensable for zygote formation. We suggest that the CpRLK1 protein is an ancient cell wall sensor that now functions to regulate osmotic pressure in the cell to allow proper gamete release. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Molecular Dynamics Study of Crystalline Swelling of Montmorillonite as Affected by Interlayer Cation Hydration

NASA Astrophysics Data System (ADS)

Li, Hongliang; Song, Shaoxian; Dong, Xianshu; Min, Fanfei; Zhao, Yunliang; Peng, Chenliang; Nahmad, Yuri

2018-04-01

Swelling of montmorillonite (Mt) is an important factor for many industrial applications. In this study, crystalline swelling of alkali-metal- and alkaline-earth-metal-Mt has been studied through energy optimization and molecular dynamics simulations using the clay force field by Materials Studio 8.0. The delamination and exfoliation of Mt are primarily realized by crystalline swelling caused by the enhanced interlayer cation hydration. The initial position of the interlayer cations and water molecules is the dominated factor for the accuracy of the Mt simulations. Crystalline swelling can be carried out in alkali-metal-Mt and Mg-Mt but with difficulty in Ca-Mt, Sr-Mt and Ba-Mt. The crystalline swelling capacity values are in the order Na-Mt > K-Mt > Cs-Mt > Mg-Mt. This order of crystalline swelling of Mt in the same group can be attributed to the differences between the interlayer cation hydration strengths. In addition, the differences in the crystalline swelling between the alkali-metal-Mt and alkaline-earth-metal-Mt can be primarily attributed to the valence of the interlayer cations.

Circus: A Replicated Procedure Call Facility

DTIC Science & Technology

1984-08-01

Computer Science Laboratory, Xerox PARC, July 1082 . [24) Bruce Ja.y Nelson. Remote Procedure Ctdl. Ph.D. dissertation, Computer Science Department...t. Ph.D. dissertation, Computer Science Division, University of California, Berkeley, Xerox PARC report number CSIF 82-7, December 1082 . [30...Tandem Computers Inc. GUARDIAN Opet’ating Sy•tem Programming Mt~nulll, Volumu 1 11nd 2. C upertino, California, 1082 . [31) R. H. Thoma.s. A majority

Aircraft Icing Handbook. Volume 3

DTIC Science & Technology

1991-03-01

Measurement," Harvard-Mt. Washington Icing Research Report, 1976-1947,L U. S. Air Materiel Command, Tech. Rept. No. 5676, 82. Findeisen , W...34Meteorological-Physical Limitations of Icing on the Atmosphere," NACA TM 885, 1939. 83. Findeisen , W., "Meteorological Commentary on D (air) 1209, Icing...November 1972, pp. 2603-2616. 58. Findeisen , W., "The Thermometric Ice Warning Indicator," (Translation) Project No. M992-B, University of Michigan

Uncertainty in Public Higher Education: Response to Stress at Ten California Colleges and Universities. A Report to the California Postsecondary Education Commission.

ERIC Educational Resources Information Center

Bowen, Frank M.; Glenny, Lyman A.

In May 1979 a survey of ten California public postsecondary institutions was undertaken, at the request of the state commission, to learn the impact of enrollment and financial uncertainty on the institutions. Surveyed were these community college districts: El Camino, Mt. San Jacinto, San Jose, San Mateo County, and San Diego; also surveyed were…

Indigenous Maori and Tongan Perspectives on the Role of Tongan Language and Culture in the Community and in the University in Aotearoa--New Zealand

ERIC Educational Resources Information Center

Kepa, Mere; Atu, Linita Manu

2006-01-01

Po Ako, a community-based project, was created to break the experience of absence--cultural alienation and educational exclusion--overwhelming the Tongan students in Aotearoa New Zealand. In January 1991, not a single Tongan student attending Mt. Roskill Grammar School in Auckland passed the national examination for a School Certificate. In May…

Durability and Intelligent Nondestructive Evaluation of Adhesive Composite Joints

DTIC Science & Technology

2000-09-22

PERFORMING ORGANIZATION NAME(S) AND ADDRESS( ES ) 8. PERFORMING ORGANIZATION University of Nebraska-Lincoln, Research Grants REPORTNUMBER & Contracts Office...Lincoln, NE 68588-0430 9. SPONSORING / MONrrORLNG AGENCY NAIME(S) AND ADDRESS( ES ) 10. SPONSORING / MONITORING AGENCY REPORT NUMBER * AFOSR 801 North...An MTS 10 MT load cell was used to measure loads. The tests were performed with a Satec spherical alignment coupling attached to the top grip. Acoustic

Proceedings: Annual Workshop on Meteorological and Environmental Inputs to Aviation Systems (4th), March 25-27, 1980.

DTIC Science & Technology

1980-03-01

Force -- 4 United States Navy -- 1 National Transportation Safety Board -- I PRIVATE SECTOR (43) University and Research -- 12 Georgia Institute of...States Air Force , Aeronautical Systems Division 6 *1 __________________________________________-our_ TABLE 4 IMPROMPTU PRESENTATIONS 񓟛 Clear Air...Propulsion Laboratory 7 concerning the Air New Zealand DC-10 accident at Mt. Erebus, Antarctica; and John Corbin of the U.S. Air Force Aeronautical

Influence of fatigue and velocity on the latency and recruitment order of scapular muscles.

PubMed

Mendez-Rebolledo, Guillermo; Gatica-Rojas, Valeska; Guzman-Muñoz, Eduardo; Martinez-Valdes, Eduardo; Guzman-Venegas, Rodrigo; Berral de la Rosa, Francisco Jose

2018-07-01

To determine the influence of velocity and fatigue on scapular muscle activation latency and recruitment order during a voluntary arm raise task, in healthy individuals. Cross-sectional study. University laboratory. Twenty three male adults per group (high-velocity and low-velocity). Onset latency of scapular muscles [Anterior deltoid (AD), lower trapezius (LT), middle trapezius (MT), upper trapezius (UT), and serratus anterior (SA)] was assessed by surface electromyography. The participants were assigned to one of two groups: low-velocity or high-velocity. Both groups performed a voluntary arm raise task in the scapular plane under two conditions: no-fatigue and fatigue. The UT showed early activation (p < 0.01) in the fatigue condition when performing the arm raise task at a high velocity. At a low velocity and with no muscular fatigue, the recruitment order was MT, LT, SA, AD, and UT. However, the recruitment order changed in the high-velocity with muscular fatigue condition, since the recruitment order was UT, AD, SA, LT, and MT. The simultaneous presence of fatigue and high-velocity in an arm raise task is associated with a decrease in the UT activation latency and a modification of the recruitment order of scapular muscles. Copyright © 2018 Elsevier Ltd. All rights reserved.

Medical Entomology Studies - X. A Revision of the Subgenus Pseudoficalbia of the Genus Uranotaenia in Southeast Asia (Diptera: Culicidae) (Contributions of the American Entomological Institute. Volume 14, Number 3)

DTIC Science & Technology

1977-01-01

rindo, Mt. Goza, Shirahama, Sonai , Yashigawa, Uehara. Ishigaki Island: Arakawa, Kabira, Mt. Banna, Mt. Maeshi, Yarabu, Yoshiwara. Bohart (1959...Mt. Goza, Shirahama, Sonai , Uehara. Ishiga ki Island: Arakawa, Mt. Banna, Mt. Kawara, Mt. Maeshi, Mt. Omoto, Yarabu Peninsula, Yoshiwara. Bohart

2. BUILDING MT76A AND MT76B FROM STREET, BUILDING MT76A IN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. BUILDING MT-76-A AND MT-76-B FROM STREET, BUILDING MT-76-A IN FOREGROUND - Fort Keogh, Livestock & Range Research Station, 3 miles west of Miles City on U.S. Highway 10, Miles City, Custer County, MT

Arsenic trioxide (ATO) influences the gene expression of metallothioneins in human glioblastoma cells.

PubMed

Falnoga, Ingrid; Zelenik Pevec, Andreja; Šlejkovec, Zdenka; Žnidarič, Magda Tušek; Zajc, Irena; Mlakar, Simona Jurković; Marc, Janja

2012-12-01

Arsenic trioxide (As(2)O(3); ATO, TRISENOX®) is used to treat patients with refractory or relapsed acute promyelocytic leukaemia while its application for treatment of solid cancers like glioblastoma is still under evaluation. In the present study, we investigated the interaction of arsenic trioxide with metallothionein (MT) isoforms as a possible (protective response) resistance of glioblastoma cells to arsenic-induced cytotoxicity. Special attention was focused on MT3, the isoform expressed mainly in the brain. MT3 has low metal inducibility, fast metal binding/releasing properties and outstanding neuronal inhibitory activity. The human astrocytoma (glioblastoma) cell line U87 MG was treated with 0.6, 2 and 6-7 μM arsenic (equivalent to 0.3, 1 and 3-3.5 μM As(2)O(3)) for 12, 24 or 48 h and gene expression for different MT isoforms, namely MT2A, MT1A, MT1F, MT1X, MT1E and MT3, was measured by real time qPCR using SYBR Green I and Taqman® gene expression assays. TfR, 18S rRNA, GAPDH and AB were tested as reference genes, and the last two evaluated to be appropriate in conditions of low (GAPDH) and high (AB) arsenic exposure. The gene expression of MT3 gene was additionally tested and confirmed by restriction enzyme analysis with PvuII. In the given conditions the mRNAs of six MT isoforms were identified in human glioblastoma cell line U87 MG. Depending on arsenic exposure conditions, an increase or decrease of MT gene expression was observed for each isoform, with the highest increase for isoforms MT1X, MT1F and MT2A mRNA (up to 13-fold) and more persistent decreases for MT1A, MT1E and MT3 mRNA. Despite the common assumption of the noninducibility of MT3, the evident MT3 mRNA increase was observed during high As exposure (up to 4-fold). In conclusion, our results clearly demonstrate the influence of As on MT isoform gene expression. The MT1X, MT1F and MT2A increase could represent brain tumour acquired resistance to As cytotoxicity while the MT3 increase is more enigmatic, with its possible involvement in arsenic-related induction of type II cell death.

Contrasting expression of membrane metalloproteinases, MT1-MMP and MT3-MMP, suggests distinct functions in skeletal development.

PubMed

Yang, Maozhou; Zhang, Bingbing; Zhang, Liang; Gibson, Gary

2008-07-01

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is the most ubiquitous and widely studied of the membrane-type metalloproteinases (MT-MMPs). It was thus surprising to find no published data on chicken MT1-MMP. We report here the characterization of the chicken gene. Its low sequence identity with the MT1-MMP genes of other species, high GC content, and divergent catalytic domain explains the absence of data and our difficulties in characterizing the gene. The absence of structural features in the chicken gene that have been suggested to be critical for the activation of MMP-2 by MT1-MMP; for the effect of MT1-MMP on cell migration and for the recycling of MT1-MMP suggest these features are either not essential or that MT1-MMP does not perform these functions in chickens. Comparison of the expression of chicken MT1-MMP with MT3-MMP and with MMP-2 and MMP-13 has confirmed the previously recognized co-expression of MT1-MMP with MMP-2 and MMP-13 in fibrous and vascular tissues, particularly those surrounding the developing long bones in other species. By contrast, MT3-MMP expression differs markedly from that of MT1-MMP and of both MMP-2 and MMP-13. MT3-MMP is expressed by chondrocytes of the developing articular surface. Similar expression patterns of this group of MT-MMPs and MMPs have been observed in mouse embryos and suggest distinct and specific functions for MT1-MMP and MT3-MMP in skeletal development.

Maternal age and ovarian stimulation independently affect oocyte mtDNA copy number and cumulus cell gene expression in bovine clones.

PubMed

Cree, Lynsey M; Hammond, Elizabeth R; Shelling, Andrew N; Berg, Martin C; Peek, John C; Green, Mark P

2015-06-01

Does maternal ageing and ovarian stimulation alter mitochondrial DNA (mtDNA) copy number and gene expression of oocytes and cumulus cells from a novel bovine model for human IVF? Oocytes collected from females with identical nuclear genetics show decreased mtDNA copy number and increased expression of an endoplasmic reticulum (ER) stress gene with repect to ovarian stimulation, whilst differences in the expression of genes involved in mitochondrial function, antioxidant protection and apoptosis were evident in relation to maternal ageing and the degree of ovarian stimulation in cumulus cells. Oocyte quality declines with advancing maternal age; however, the underlying mechanism, as well as the effects of ovarian stimulation are poorly understood. Human studies investigating these effects are often limited by differences in age and ovarian stimulation regimens within a patient cohort, as well as genetic and environmental variability. A novel bovine cross-sectional maternal age model for human IVF was undertaken. Follicles were aspirated from young (3 years of age; n = 7 females) and old (10 years of age; n = 5 females) Holstein Freisian clones following multiple unstimulated, mild and standard ovarian stimulation cycles. These bovine cloned females were generated by the process of somatic cell nuclear transfer (SCNT) from the same founder and represent a homogeneous population with reduced genetic and environmental variability. Maternal age and ovarian stimulation effects were investigated in relation to mtDNA copy number, and the expression of 19 genes involved in mitochondrial function, antioxidant protection, oocyte-cumulus cell signalling and follicle development in both oocytes and cumulus cells. Young (3 years of age; n = 7 females) and old (10 years of age; n = 5 females) Holstein Freisian bovine clones were maintained as one herd. Stimulation cycles were based on the long GnRH agonist down-regulation regimen used in human fertility clinics. Follicle growth rates, numbers and diameters were monitored by ultrasonography and aspirated when the lead follicles were >14 mm in diameter. Follicle characteristics were analysed using a mixed model procedure. Quantitative PCR (qPCR) was used to determine mtDNA copy number and reverse transcriptase-qPCR (RT-qPCR) was used to measure gene expression in oocytes and cumulus cells. Method of ovarian stimulation (P = 0.04), but not maternal age (P > 0.1), was associated with a lower mtDNA copy number in oocytes. Neither factor affected mtDNA copy number in cumulus cells. In oocytes, maternal age had no effect on gene expression; however, ovarian stimulation in older females increased the expression of GRP78 (P = 0.02), a gene involved in ER stress. In cumulus cells, increasing maternal age was associated with the higher expression of genes involved in mitochondrial maintenance (TXN2 P = 0.008 and TFAM P = 0.03), whereas ovarian stimulation decreased the expression of genes involved in mitochondrial oxidative stress and apoptosis (TXN2 P = 0.002, PRDX3 P = 0.03 and BAX P = 0.03). The low number of oocyte and cumulus cell samples collected from the unstimulated cycles limited the analysis. Fertilization and developmental potential of the oocytes was not assessed because these were used for mtDNA and gene expression quantification. Delineation of the independent effects of maternal age and ovarian stimulation regimen on mtDNA copy number gene expression in oocytes and cumulus cells was enabled by the removal of genetic and environmental variability in this bovine model for human IVF. Therefore, these extend upon previous knowledge and findings provide relevant insights that are applicable for improving human ovarian stimulation regimens. Funding was provided by Fertility Associates and the University of Auckland. J.C.P. is a shareholder of Fertility Associates and M.P.G. received a fellowship from Fertility Associates. The other authors of this manuscript declare no conflict of interest that could be perceived as prejudicing the impartiality of the reported research. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cytoplasmic transfer of heritable elements other than mtDNA from SAMP1 mice into mouse tumor cells suppresses their ability to form tumors in C57BL6 mice.

PubMed

Shimizu, Akinori; Tani, Haruna; Takibuchi, Gaku; Ishikawa, Kaori; Sakurazawa, Ryota; Inoue, Takafumi; Hashimoto, Tetsuo; Nakada, Kazuto; Takenaga, Keizo; Hayashi, Jun-Ichi

2017-11-04

In a previous study, we generated transmitochondrial P29mtSAMP1 cybrids, which had nuclear DNA from the C57BL6 (referred to as B6) mouse strain-derived P29 tumor cells and mitochondrial DNA (mtDNA) exogenously-transferred from the allogeneic strain SAMP1. Because P29mtSAMP1 cybrids did not form tumors in syngeneic B6 mice, we proposed that allogeneic SAMP1 mtDNA suppressed tumor formation of P29mtSAMP1 cybrids. To test this hypothesis, current study generated P29mt(sp)B6 cybrids carrying all genomes (nuclear DNA and mtDNA) from syngeneic B6 mice by eliminating SAMP1 mtDNA from P29mtSAMP1 cybrids and reintroducing B6 mtDNA. However, the P29mt(sp)B6 cybrids did not form tumors in B6 mice, even though they had no SAMP1 mtDNA, suggesting that SAMP1 mtDNA is not involved in tumor suppression. Then, we examined another possibility of whether SAMP1 mtDNA fragments potentially integrated into the nuclear DNA of P29mtSAMP1 cybrids are responsible for tumor suppression. We generated P29 H (sp)B6 cybrids by eliminating nuclear DNA from P29mt(sp)B6 cybrids and reintroducing nuclear DNA with no integrated SAMP1 mtDNA fragment from mtDNA-less P29 cells resistant to hygromycin in selection medium containing hygromycin. However, the P29 H (sp)B6 cybrids did not form tumors in B6 mice, even though they carried neither SAMP1 mtDNA nor nuclear DNA with integrated SAMP1 mtDNA fragments. Moreover, overproduction of reactive oxygen species (ROS) and bacterial infection were not involved in tumor suppression. These observations suggest that tumor suppression was caused not by mtDNA with polymorphic mutations or infection of cytozoic bacteria but by hypothetical heritable cytoplasmic elements other than mtDNA from SAMP1 mice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Examining the specific contributions of individual Arabidopsis metallothioneins to copper distribution and metal tolerance.

PubMed

Guo, Woei-Jiun; Meetam, Metha; Goldsbrough, Peter B

2008-04-01

Metallothioneins (MTs) are small cysteine-rich proteins found in various eukaryotes. Plant MTs are classified into four types based on the arrangement of cysteine residues. To determine whether all four types of plant MTs function as metal chelators, six Arabidopsis (Arabidopsis thaliana) MTs (MT1a, MT2a, MT2b, MT3, MT4a, and MT4b) were expressed in the copper (Cu)- and zinc (Zn)-sensitive yeast mutants, Deltacup1 and Deltazrc1 Deltacot1, respectively. All four types of Arabidopsis MTs provided similar levels of Cu tolerance and accumulation to the Deltacup1 mutant. The type-4 MTs (MT4a and MT4b) conferred greater Zn tolerance and higher accumulation of Zn than other MTs to the Deltazrc1 Deltacot1 mutant. To examine the functions of MTs in plants, we studied Arabidopsis plants that lack MT1a and MT2b, two MTs that are expressed in phloem. The lack of MT1a, but not MT2b, led to a 30% decrease in Cu accumulation in roots of plants exposed to 30 mum CuSO(4). Ectopic expression of MT1a RNA in the mt1a-2 mt2b-1 mutant restored Cu accumulation in roots. The mt1a-2 mt2b-1 mutant had normal metal tolerance. However, when MT deficiency was combined with phytochelatin deficiency, growth of the mt1a-2 mt2b-1 cad1-3 triple mutant was more sensitive to Cu and cadmium compared to the cad1-3 mutant. Together these results provide direct evidence for functional contributions of MTs to plant metal homeostasis. MT1a, in particular, plays a role in Cu homeostasis in the roots under elevated Cu. Moreover, MTs and phytochelatins function cooperatively to protect plants from Cu and cadmium toxicity.

Dedicated Pediatricians in Emergency Department: Shorter Waiting Times and Lower Costs

PubMed Central

Melo, Manuel Rocha; Ferreira-Magalhães, Manuel; Flor-Lima, Filipa; Rodrigues, Mariana; Severo, Milton; Almeida-Santos, Luis; Caldas-Afonso, Alberto; Barros, Pedro Pita; Ferreira, António

2016-01-01

Background Dedicated pediatricians in emergency departments (EDs) may be beneficial, though no previous studies have assessed the related costs and benefits/harms. We aimed to evaluate the net benefits and costs of dedicated emergency pediatricians in a pediatric ED. Methods Cost-consequences analysis of visits to a pediatric ED of a tertiary hospital. Two pediatric ED Medical Teams (MT) were compared: MT-A (May–September 2012), with general pediatrics physicians only; and MT-B (May–September 2013), with emergency dedicated pediatricians. The main outcomes analyzed were relevant clinical outcomes, patient throughput time and costs. Results We included 8,694 children in MT-A and 9,417 in MT-B. Medication use in the ED increased from 42.3% of the children in MT-A to 49.6% in MT-B; diagnostic tests decreased from 24.2% in MT-A to 14.3% in MT-B. Hospitalization increased from 1.3% in MT-A to 3.0% in MT-B; however, there was no significant difference in diagnosis-related group relative weight of hospitalized children in MT-A and MT-B (MT-A, 0.979; MT-B, 1.075). No differences were observed in ED readmissions or in patients leaving without being seen by a physician. The patient throughput time was significantly shorter in MT-B, with faster times to first medical observation. Within the cost domains analyzed, the total expenditures per children observed in the ED were 16% lower in MT-B: 37.87 euros in MT-A; 31.97 euros in MT-B. Conclusion The presence of dedicated emergency pediatricians in a pediatric ED was associated with significantly lower waiting times in the ED, reduced costs, and similar clinical outcomes. PMID:27564093

The PICASSO project: MT Investigation in Southern Spain and Morocco - Results of phase I and outlook on phase II

NASA Astrophysics Data System (ADS)

Kiyan, D.; Schmoldt, J.; Jones, A. G.; Hogg, C.; Rosell, O.

2009-12-01

PICASSO (Project to Investigate Convective Alboran Sea System Overturn) is an international, multi-disciplinary project that aims to improve knowledge of the internal structure and plate-tectonic processes in the highly complex three-dimensional region formed by the collision of the African and European plate under the effect of the Mediterranean plate motion. The first phase of the DIAS magnetotelluric (MT) component of the PICASSO project was carried out in Southern Spain from Sept.-Nov., 2007 focused on the investigation of the internal structure of the Betic Mountain Chain and the Iberian Basement. Two different types of magnetotelluric (MT) equipment - broadband (BBMT) and long period (LMT) MT - were used along a profile from the outskirts of Madrid to the Mediterranean Sea through the Betic Mountain Chain. The modified acquisition design of one of the equipment types (the LVIV LEMI long period system), with separate recording of each telluric channel, allowed for advanced investigation of the acquired dataset. The data were processed using four different robust algorithms, and the different responses have been compared. A distinct separation can be made between the Betics region of Alpine orogeny in the south and the Variscan Iberian Massif beneath the north of the profile in terms of their inherent electric conductivity characteristics. Models derived by two-dimensional inversions of regional responses, after removing distortion effects, from this first phase show a remarkably complex subsurface structure beneath the region of the External Betic Chain. Strike direction varies along the profile and with depth due to the intricate morphology, and its choice has significant impact on the responses to be modelled and thereby provides a challenging framework for MT data interpretation. The second phase of PICASSO aims to shed light onto the origin of the Atlas Mountain Chain and test hypotheses for its missing mantle root derived from heat flow, gravity, geoid and topography observations. The MT investigation scheduled for the period end-September to end-November comprises two long period profiles, N-S through Meknes and NW-SE through Marrakesh. Additional broadband surveys will be carried out at the same time in collaboration with partners from the Universities of Barcelona and Bari in order to investigate the crustal structure of the Atlas Mountains.

75 FR 43556 - TA-W-73,381, MT Rail Link, Inc., Missoula, MT; TA-W-73,381A, Billings, MT; TA-W-73,381B, Laurel...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-26

... DEPARTMENT OF LABOR Employment and Training Administration TA-W-73,381, MT Rail Link, Inc., Missoula, MT; TA-W-73,381A, Billings, MT; TA-W-73,381B, Laurel, MT; TA-W-73,381C, Livingston, MT; TA-W-73... Helena, Montana. The amended notice applicable to TA-W-73,381 is hereby issued as follows: All workers of...

Remote Control by Inter-Enzyme Allostery: A Novel Paradigm for Regulation of the Shikimate Pathway.

PubMed

Munack, Steffi; Roderer, Kathrin; Ökvist, Mats; Kamarauskaite, Jurate; Sasso, Severin; van Eerde, André; Kast, Peter; Krengel, Ute

2016-03-27

DAHP synthase and chorismate mutase catalyze key steps in the shikimate biosynthetic pathway en route to aromatic amino acids. In Mycobacterium tuberculosis, chorismate mutase (MtCM; Rv0948c), located at the branch point toward phenylalanine and tyrosine, has poor activity on its own. However, it is efficiently activated by the first enzyme of the pathway, DAHP synthase (MtDS; Rv2178c), through formation of a non-covalent MtCM-MtDS complex. Here, we show how MtDS serves as an allosteric platform for feedback regulation of both enzymes, using X-ray crystallography, small-angle X-ray scattering, size-exclusion chromatography, and multi-angle light scattering. Crystal structures of the fully inhibited MtDS and the allosterically down-regulated MtCM-MtDS complex, solved at 2.8 and 2.7Å, respectively, reveal how effector binding at the internal MtDS subunit interfaces regulates the activity of MtDS and MtCM. While binding of all three metabolic end products to MtDS shuts down the entire pathway, the binding of phenylalanine jointly with tyrosine releases MtCM from the MtCM-MtDS complex, hence suppressing MtCM activation by 'inter-enzyme allostery'. This elegant regulatory principle, invoking a transient allosteric enzyme interaction, seems to be driven by dynamics and is likely a general strategy used by nature. Copyright © 2016 Elsevier Ltd. All rights reserved.

mtDNAmanager: a Web-based tool for the management and quality analysis of mitochondrial DNA control-region sequences

PubMed Central

Lee, Hwan Young; Song, Injee; Ha, Eunho; Cho, Sung-Bae; Yang, Woo Ick; Shin, Kyoung-Jin

2008-01-01

Background For the past few years, scientific controversy has surrounded the large number of errors in forensic and literature mitochondrial DNA (mtDNA) data. However, recent research has shown that using mtDNA phylogeny and referring to known mtDNA haplotypes can be useful for checking the quality of sequence data. Results We developed a Web-based bioinformatics resource "mtDNAmanager" that offers a convenient interface supporting the management and quality analysis of mtDNA sequence data. The mtDNAmanager performs computations on mtDNA control-region sequences to estimate the most-probable mtDNA haplogroups and retrieves similar sequences from a selected database. By the phased designation of the most-probable haplogroups (both expected and estimated haplogroups), mtDNAmanager enables users to systematically detect errors whilst allowing for confirmation of the presence of clear key diagnostic mutations and accompanying mutations. The query tools of mtDNAmanager also facilitate database screening with two options of "match" and "include the queried nucleotide polymorphism". In addition, mtDNAmanager provides Web interfaces for users to manage and analyse their own data in batch mode. Conclusion The mtDNAmanager will provide systematic routines for mtDNA sequence data management and analysis via easily accessible Web interfaces, and thus should be very useful for population, medical and forensic studies that employ mtDNA analysis. mtDNAmanager can be accessed at . PMID:19014619

Modeled MT Resistivity Data for the McGregor Range, New Mexico

DOE Data Explorer

Nash, Greg; Wannamaker, Phil; Maris, Virginia

2017-04-30

This is the inversion resistivity data from a magnetotelluric survey done as part of Phase 2 Tularosa Basin, New Mexico, geothermal play fairway analysis. The data covers part of McGregor Range, Fort Bliss. The inversion was done by Phil Wannamaker and Virginia Maris of the Energy & Geoscience Institute at the University of Utah. The data are contained in a text file and data coordinates represent grid cell centers.

Heterobivalent Imaging Agents Targeting Prostate Cancer Training

DTIC Science & Technology

2011-06-01

has been implicated as a salient player in the pathobiology of cancers of epithelial origin, e.g. prostate, cervix , ovarian, colon and...ANSI Std. Z39.18 W81XWH-10-1-0481 Heterobivalent Imaging Agents Targeting Prostate Cancer Training Aaron LeBeau University of California, San...Francisco San Francisco, CA 94103 Annual Summary 31 MAY 2010 - 1JUN 201101-06-2011 To determine the utility of imaging MT-SP1 in cancer , xenografts of

The Trouble with MEAM2: Implications of Pseudogenes on Species Delimitation in the Globally Invasive Bemisia tabaci (Hemiptera: Aleyrodidae) Cryptic Species Complex.

PubMed

Tay, Wee Tek; Elfekih, Samia; Court, Leon N; Gordon, Karl H J; Delatte, Hélène; De Barro, Paul J

2017-10-01

Molecular species identification using suboptimal PCR primers can over-estimate species diversity due to coamplification of nuclear mitochondrial (NUMT) DNA/pseudogenes. For the agriculturally important whitefly Bemisia tabaci cryptic pest species complex, species identification depends primarily on characterization of the mitochondrial DNA cytochrome oxidase I (mtDNA COI) gene. The lack of robust PCR primers for the mtDNA COI gene can undermine correct species identification which in turn compromises management strategies. This problem is identified in the B. tabaci Africa/Middle East/Asia Minor clade which comprises the globally invasive Mediterranean (MED) and Middle East Asia Minor I (MEAM1) species, Middle East Asia Minor 2 (MEAM2), and the Indian Ocean (IO) species. Initially identified from the Indian Ocean island of Réunion, MEAM2 has since been reported from Japan, Peru, Turkey and Iraq. We identified MEAM2 individuals from a Peruvian population via Sanger sequencing of the mtDNA COI gene. In attempting to characterize the MEAM2 mitogenome, we instead characterized mitogenomes of MEAM1. We also report on the mitogenomes of MED, AUS, and IO thereby increasing genomic resources for members of this complex. Gene synteny (i.e., same gene composition and orientation) was observed with published B. tabaci cryptic species mitogenomes. Pseudogene fragments matching MEAM2 partial mtDNA COI gene exhibited low frequency single nucleotide polymorphisms that matched low copy number DNA fragments (<3%) of MEAM1 genomes, whereas presence of internal stop codons, loss of expected stop codons and poor primer annealing sites, all suggested MEAM2 as a pseudogene artifact and so not a real species. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Evaluation of the mtDNA-COII Region Based Species Specific Assay for Identifying Members of the Anopheles culicifacies Species Complex

PubMed Central

Manonmani, Arulsamy Mary; Mathivanan, Ashok Kumar; Sadanandane, Candassamy; Jambulingam, Purushothaman

2013-01-01

Background: Anopheles culicifacies, a major malarial vector has been recognized as a complex of five sibling species, A, B, C, D and E. These sibling species exhibit varied vectorial capacity, host specificity and susceptibility to malarial parasites/ insecticides. In this study, a PCR assay developed earlier for distinguishing the five individual species was validated on samples of An. culicifacies collected from various parts of India. Methods: The samples were initially screened using the rDNA-ITS2 region based primers which categorised the samples into either A/D group or B/C/E group. A proportion of samples belonging to each group were subjected to the mtDNA-COII PCR assay for identifying individual species. Results: Among the 615 samples analysed by rDNA-ITS2 PCR assay, 303 were found to belong to A/D group and 299 to B/C/E group while 13 turned negative. Among 163 samples belonging to A/D group, only one sample displayed the profile characteristic of species A and among the 176 samples falling in the B/C/E group, 51 were identified as species B, 14 as species C and 41 as species E respectively by the mtDNA-COII PCR assay. Samples exhibiting products diagnostic of B/C/E, when subjected to PCR-RFLP assay identified 15 samples as species E. Conclusion: Validation of the mtDNA-COII PCR assay on large number of samples showed that this technique cannot be used universally to distinguish the 5 members of this species complex, as it has been designed based on minor/single base differences observed in the COII region. PMID:24409441

Investigating the 'Iron Hypothesis' in the North Pacific: Trans-Pacific Dust and Methanesulfonate (MSA) in the Denali Ice Core, Alaska

NASA Astrophysics Data System (ADS)

Saylor, P. L.; Osterberg, E. C.; Winski, D.; Ferris, D. G.; Koffman, B. G.; Kreutz, K. J.; Wake, C. P.; Campbell, S. W.

2015-12-01

Oceanic deposition of Asian-sourced, Iron-rich dust particulate has been linked to enhanced phytoplankton productivity in regions of the Pacific Ocean. High Nutrient Low Chlorophyll (HNLC) ocean regions, such as the North Pacific, are hypothesized to play a significant role in changing atmospheric CO­2 concentrations on glacial-interglacial timescales. Phytoplankton blooms generate methanesulfonate (MSA), an atmospheric oxidation product of dimethylsulfide (DMS) that is readily aerosolized and deposited in nearby glacial ice. In the summer of 2013, an NSF-funded team from Dartmouth College and the Universities of Maine and New Hampshire collected two 1000 year-long parallel ice cores to bedrock from the summit plateau of Mount Hunter in Denali National Park, Alaska (62.940° N, 151.088° W, 3912 m elevation). The Mt. Hunter ice core site is well situated to record changes in trans-Pacific dust flux and MSA emissions in the North Pacific. Here we investigate the history of dust flux to Denali over the last millennium using major and trace element chemistry and microparticle concentration and size distribution data from the Mt. Hunter cores. We evaluate potential controlling mechanisms on Denali dust flux including conditions at Asian dust sources (storminess, wind speed, precipitation), the strength of the Aleutian Low, and large-scale climate modes such as the El Niño-Southern Oscillation and the Pacific Decadal Oscillation. We also evaluate the Mt. Hunter record for relationships between dust flux and MSA concentrations to investigate whether dust fertilization enhanced North Pacific phytoplankton production over the past 1000 years. Future work will create a composite North Pacific dust record using new and existing Mt. Logan ice core records to evaluate these relationships over the entire Holocene.

Unravelling the Genetic Diversity among Cassava Bemisia tabaci Whiteflies Using NextRAD Sequencing.

PubMed

Wosula, Everlyne N; Chen, Wenbo; Fei, Zhangjun; Legg, James P

2017-11-01

Bemisia tabaci threatens production of cassava in Africa through vectoring viruses that cause cassava mosaic disease (CMD) and cassava brown streak disease (CBSD). B. tabaci sampled from cassava in eight countries in Africa were genotyped using NextRAD sequencing, and their phylogeny and population genetics were investigated using the resultant single nucleotide polymorphism (SNP) markers. SNP marker data and short sequences of mitochondrial DNA cytochrome oxidase I (mtCOI) obtained from the same insect were compared. Eight genetically distinct groups were identified based on mtCOI, whereas phylogenetic analysis using SNPs identified six major groups, which were further confirmed by PCA and multidimensional analyses. STRUCTURE analysis identified four ancestral B. tabaci populations that have contributed alleles to the six SNP-based groups. Significant gene flows were detected between several of the six SNP-based groups. Evidence of gene flow was strongest for SNP-based groups occurring in central Africa. Comparison of the mtCOI and SNP identities of sampled insects provided a strong indication that hybrid populations are emerging in parts of Africa recently affected by the severe CMD pandemic. This study reveals that mtCOI is not an effective marker at distinguishing cassava-colonizing B. tabaci haplogroups, and that more robust SNP-based multilocus markers should be developed. Significant gene flows between populations could lead to the emergence of haplogroups that might alter the dynamics of cassava virus spread and disease severity in Africa. Continuous monitoring of genetic compositions of whitefly populations should be an essential component in efforts to combat cassava viruses in Africa. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Everyday Multitasking Abilities in Older HIV+ Adults: Neurobehavioral Correlates and the Mediating Role of Metacognition.

PubMed

Fazeli, P L; Casaletto, K B; Woods, S P; Umlauf, A; Scott, J C; Moore, D J

2017-12-01

The prevalence of older adults living with HIV is rising, as is their risk for everyday functioning problems associated with neurocognitive dysfunction. Multitasking, the ability to maintain and carry out subgoals in support of a larger goal, is a multidimensional skill ubiquitous during most real-life tasks and associated with prefrontal networks that are vulnerable in HIV. Understanding factors associated with multitasking will improve characterization of HIV-associated neurocognitive disorders. Metacognition is also associated with frontal systems, is impaired among individuals with HIV, and may contribute to multitasking. Ninety-nine older (≥50 years) adults with HIV completed: the Everyday Multitasking Test (MT), a performance-based measure during which participants concurrently attempt four everyday tasks (e.g., medication management) within a time limit; a comprehensive neuropsychological battery; measures of metacognition regarding their MT performance (e.g., metacognitive knowledge and online awareness). Better global neuropsychological performance (i.e., average T-score across all domains) was associated with better Everyday MT total scores (rho = 0.34; p < .001), as was global metacognition (rho = 0.37, p < .01). Bootstrapping mediation analysis revealed global metacognition was a significant partial mediator between neurocognition and Everyday MT (b = 0.09, 95% confidence interval [CI] = 0.01, 0.25). Specifically, metacognitive knowledge (but not online awareness) drove this mediation (b = 0.13, 95% CI = 0.03, 0.27). Consistent with findings among younger persons with HIV, neuropsychological performance is strongly associated with a complex, laboratory-based test of everyday multitasking, and metacognition of task performance was a pathway through which successful multitasking occurred. Interventions aimed at modifying metacognition to improve daily functioning may be warranted among older adults with HIV. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of Intravenous Patient-Controlled Sufentanil Analgesia and Music Therapy on Pain and Hemodynamics After Surgery for Lung Cancer: A Randomized Parallel Study.

PubMed

Wang, Yichun; Tang, Haoke; Guo, Qulian; Liu, Jingshi; Liu, Xiaohong; Luo, Junming; Yang, Wenqian

2015-11-01

Postoperative pain is caused by surgical injury and trauma; is stressful to patients; and includes a series of physiologic, psychological, and behavioral reactions. Effective postoperative analgesia helps improve postoperative pain, perioperative safety, and hospital discharge rates. This study aimed to observe the influence of postoperative intravenous sufentanil patient-controlled analgesia combined with music therapy versus sufentanil alone on hemodynamics and analgesia in patients with lung cancer. This was a randomized parallel study performed in 60 patients in American Society of Anesthesiologists class I or II undergoing lung cancer resection at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University. Patients were randomly assigned to a music therapy (MT) group and a control (C) group. The MT group underwent preoperative and postoperative music intervention while the C group did not. Both groups received intravenous patient-controlled sufentanil analgesia. The primary outcome was the visual analogue scale (VAS) score at 24 hours after surgery. The secondary outcomes included hemodynamic changes (systolic blood pressure, diastolic blood pressure, heart rate), changes on the Self-Rating Anxiety Scale (SAS), total consumption of sufentanil, number of uses, sedation, and adverse effects. The postoperative sufentanil dose and analgesia frequency were recorded. Compared with the C group, the MT group had significantly lower VAS score, systolic and diastolic blood pressure, heart rate, and SAS score within 24 hours after surgery (p < 0.01). In addition, postoperative analgesia frequency and sufentanil dose were reduced in the MT group (p < 0.01). Combined music therapy and sufentanil improves intravenous patient-controlled analgesia effects compared with sufentanil alone after lung cancer surgery. Lower doses of sufentanil could be administered to more effectively improve patients' cardiovascular parameters.

Molecular, dynamic, and structural origin of inhomogeneous magnetization transfer in lipid membranes.

PubMed

Swanson, Scott D; Malyarenko, Dariya I; Fabiilli, Mario L; Welsh, Robert C; Nielsen, Jon-Fredrik; Srinivasan, Ashok

2017-03-01

To elucidate the dynamic, structural, and molecular properties that create inhomogeneous magnetization transfer (ihMT) contrast. Amphiphilic lipids, lamellar phospholipids with cholesterol, and bovine spinal cord (BSC) specimens were examined along with nonlipid systems. Magnetization transfer (MT), enhanced MT (eMT, obtained with double-sided radiofrequency saturation), ihMT (MT - eMT), and dipolar relaxation, T 1D , were measured at 2.0 and 11.7 T. The amplitude of ihMT ratio (ihMTR) is positively correlated with T 1D values. Both ihMTR and T 1D increase with increasing temperature in BSC white matter and in phospholipids and decrease with temperature in other lipids. Changes in ihMTR with temperature arise primarily from alterations in MT rather than eMT. Spectral width of MT, eMT, and ihMT increases with increasing carbon chain length. Concerted motions of phospholipids in white matter decrease proton spin diffusion leading to increased proton T 1D times and increased ihMT amplitudes, consistent with decoupling of Zeeman and dipolar spin reservoirs. Molecular specificity and dynamic sensitivity of ihMT contrast make it a suitable candidate for probing myelin membrane disorders. Magn Reson Med 77:1318-1328, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Combining Afferent Stimulation and Mirror Therapy for Improving Muscular, Sensorimotor, and Daily Functions After Chronic Stroke: A Randomized, Placebo-Controlled Study.

PubMed

Lee, Ya-yun; Lin, Keh-chung; Wu, Ching-yi; Liao, Ching-hua; Lin, Jui-chi; Chen, Chia-ling

2015-10-01

Mirror therapy (MT) combined with mesh glove (MG) afferent stimulation (MT + MG) has been suggested as an effective intervention for motor recovery in patients with stroke. This study aimed to further determine the treatment effects of the MT + MG approach on muscular properties, sensorimotor functions, and daily function. This was a single-blind, randomized, placebo-controlled study. Forty-eight participants with chronic stroke were recruited from medical centers and were randomly assigned to the MT, MT + MG, and MT with sham MG stimulation (MT + sham) groups. The intervention consisted of 1.5 hrs/day, 5 days/wk for 4 wks. Primary outcomes were the Fugl-Meyer Assessment and muscular properties (muscle tone and stiffness). Secondary outcomes included measures of sensorimotor and daily functions. Compared with the MT and MT + sham groups, the MT + MG group demonstrated improved muscular properties. The MT + MG and MT + sham groups showed greater improvement in manual dexterity and daily function than the MT group did. No beneficial effects on the Fugl-Meyer Assessment and other sensorimotor outcomes were found for the MT + MG group. Although no significant group differences were found in the Fugl-Meyer Assessment, MT + MG induced distinctive effects on muscular properties, manual dexterity, and daily function.

The efficacy of manual therapy and exercise for treating non-specific neck pain: A systematic review.

PubMed

Hidalgo, Benjamin; Hall, Toby; Bossert, Jean; Dugeny, Axel; Cagnie, Barbara; Pitance, Laurent

2017-11-06

To review and update the evidence for different forms of manual therapy (MT) and exercise for patients with different stages of non-specific neck pain (NP). MEDLINE, Cochrane-Register-of-Controlled-Trials, PEDro, EMBASE. A qualitative systematic review covering a period from January 2000 to December 2015 was conducted according to updated-guidelines. Specific inclusion criteria only on RCTs were used; including differentiation according to stages of NP (acute - subacute [ASNP] or chronic [CNP]), as well as sub-classification based on type of MT interventions: MT1 (HVLA manipulation); MT2 (mobilization and/or soft-tissue-techniques); MT3 (MT1 + MT2); and MT4 (Mobilization-with-Movement). In each sub-category, MT could be combined or not with exercise and/or usual medical care. Initially 121 studies were identified for potential inclusion. Based on qualitative and quantitative evaluation criteria, 23 RCTs were identified for review. Evidence for ASNP: MODERATE-evidence: In favour of (i) MT1 to the cervical spine (Cx) combined with exercises when compared to MT1 to the thoracic spine (Tx) combined with exercises; (ii) MT3 to the Cx and Tx combined with exercise compared to MT2 to the Cx with exercise or compared to usual medical care for pain and satisfaction with care from short to long-term. Evidence for CNP: STRONG-evidence: Of no difference of efficacy between MT2 at the symptomatic Cx level(s) in comparison to MT2 on asymptomatic Cx level(s) for pain and function. MODERATE to STRONG-evidence: In favour of MT1 and MT3 on Cx and Tx with exercise in comparison to exercise or MT alone for pain, function, satisfaction with care and general-health from short to moderate-terms. MODERATE-evidence: In favour (i) of MT1 as compared to MT2 and MT4, all applied to the Cx, for neck mobility, and pain in the very short term; (ii) of MT2 using sof-tissue-techniques to the Cx and Tx or MT3 to the Cx and Tx in comparison to no-treatment in the short-term for pain and disability. This systematic review updates the evidence for MT combined or not with exercise and/or usual medical care for different stages of NP and provides recommendations for future studies. Two majors points could be highlighted, the first one is that combining different forms of MT with exercise is better than MT or exercise alone, and the second one is that mobilization need not be applied at the symptomatic level(s) for improvements of NP patients. These both points may have clinical implications for reducing the risk involved with some MT techniques applied to the cervical spine.

A Reflight of the Explorer-1 Science Mission: The Montana EaRth Orbiting Pico Explorer (MEROPE)

NASA Astrophysics Data System (ADS)

Klumpar, D. M.; Obland, M.; Hunyadi, G.; Jepsen, S.; Larsen, B.; Kankelborg, C.; Hiscock, W.

2001-05-01

Montana State University's interdisciplinary Space Science and Engineering Laboratory (SSEL) under support from the Montana NASA Space Grant Consortium is engaged in an earth orbiting satellite student design and flight project. The Montana EaRth Orbiting Pico Explorer (MEROPE) will carry a modern-day reproduction of the scientific payload carried on Explorer-1. On February 1, 1958 the United States launched its first earth orbiting satellite carrying a 14 kg scientific experiment built by Professor James Van Allen's group at the State University of Iowa (now The University of Iowa). The MEROPE student satellite will carry a reproduction, using current-day technology, of the scientific payload flown on Explorer-1. The CubeSat-class satellite will use currently available, low cost technologies to produce a payload-carrying satellite with a total orbital mass of 1 kg in a volume of 1 cubic liter. The satellite is to be launched in late 2001 into a 600 km, 65° inclination orbit. MEROPE will utilize passive magnetic orientation for 2-axis attitude control. A central microprocessor provides timing, controls on-board operations and switching, and enables data storage. Body mounted GaAs solar arrays are expected to provide in excess of 1.5 W. to maintain battery charge and operate the bus and payload. The Geiger counter will be operated at approximately 50% duty cycle, primarily during transits of the earth's radiation belts. Data will be stored on board and transmitted approximately twice per day to a ground station located on the Bozeman campus of the Montana State University. Owing to the 65° inclination, the instrument will also detect the higher energy portion of the electron spectrum responsible for the production of the Aurora Borealis. This paper describes both the technical implementation and design of the satellite and its payload as well as the not inconsiderable task of large team organization and management. As of March 2001, the student team consists of four graduate students and approximately 45 undergraduates in fields including Physics, Engineering, Computer Sciences, Business, and Liberal Arts. Satellites of this class have the potential to lead to low-cost constellations of sciencecraft making coordinated measurements of the highly dynamic and spatially structured space environment. While key tradeoffs between resource needs and resource availability (e.g. power, telemetry, mass, volume, and cost) constrain payload sophistication, the tremendous advantages of having even simple dispersed multipoint measurements of the Geospace environment far outweigh the loss of payload sophistication in many instances.

Opposing Control by Transcription Factors MYB61 and MYB3 Increases Freezing Tolerance by Relieving C-Repeat Binding Factor Suppression1[OPEN

PubMed Central

Zhang, Yunqin; Miao, Zhenyan; Xie, Can; Meng, Xiangzhao; Deng, Jie; Mysore, Kirankumar S.; Frugier, Florian; Wang, Tao

2016-01-01

Cold acclimation is an important process by which plants respond to low temperature and enhance their winter hardiness. C-REPEAT BINDING FACTOR1 (CBF1), CBF2, and CBF3 genes were shown previously to participate in cold acclimation in Medicago truncatula. In addition, MtCBF4 is transcriptionally induced by salt, drought, and cold stresses. We show here that MtCBF4, shown previously to enhance drought and salt tolerance, also positively regulates cold acclimation and freezing tolerance. To identify molecular factors acting upstream and downstream of the MtCBF4 transcription factor (TF) in cold responses, we first identified genes that are differentially regulated upon MtCBF4 overexpression using RNAseq Digital Gene Expression Profiling. Among these, we showed that MtCBF4 directly activates the transcription of the COLD ACCLIMATION SPECIFIC15 (MtCAS15) gene. To gain insights into how MtCBF4 is transcriptionally regulated in response to cold, an R2R3-MYB TF, MtMYB3, was identified based on a yeast one-hybrid screen as binding directly to MYB cis-elements in the MtCBF4 promoter, leading to the inhibition of MtCBF4 expression. In addition, another MYB TF, MtMYB61, identified as an interactor of MtMYB3, can relieve the inhibitory effect of MtMYB3 on MtCBF4 transcription. This study, therefore, supports a model describing how MtCBF4 is regulated by antagonistic MtMYB3/MtMYB61 TFs, leading to the up-regulation of downstream targets such as MtCAS15 acting in cold acclimation in M. truncatula. PMID:27578551

Assessment of metallothionein and antibodies to metallothionein in normal and autistic children having exposure to vaccine-derived thimerosal.

PubMed

Singh, Vijendra K; Hanson, Jeff

2006-06-01

Allergic autoimmune reaction after exposure to heavy metals such as mercury may play a causal role in autism, a developmental disorder of the central nervous system. As metallothionein (MT) is the primary metal-detoxifying protein in the body, we conducted a study of the MT protein and antibodies to metallothionein (anti-MT) in normal and autistic children whose exposure to mercury was only from thimerosal-containing vaccines. Laboratory analysis by immunoassays revealed that the serum level of MT did not significantly differ between normal and autistic children. Furthermore, autistic children harboured normal levels of anti-MT, including antibodies to isoform MT-I (anti-MT-I) and MT-II (anti-MT-II), without any significant difference between normal and autistic children. Our findings indicate that because autistic children have a normal profile of MT and anti-MT, the mercury-induced autoimmunity to MT may not be implicated in the pathogenesis of autism.

mtDNA, Metastasis, and the Mitochondrial Unfolded Protein Response (UPRmt).

PubMed

Kenny, Timothy C; Germain, Doris

2017-01-01

While several studies have confirmed a link between mitochondrial DNA (mtDNA) mutations and cancer cell metastasis, much debate remains regarding the nature of the alternations in mtDNA leading to this effect. Meanwhile, the mitochondrial unfolded protein response (UPR mt ) has gained much attention in recent years, with most studies of this pathway focusing on its role in aging. However, the UPR mt has also been studied in the context of cancer. More recent work suggests that rather than a single mutation or alternation, specific combinatorial mtDNA landscapes able to activate the UPR mt may be those that are selected by metastatic cells, while mtDNA landscapes unable to activate the UPR mt do not. This review aims at offering an overview of the confusing literature on mtDNA mutations and metastasis and the more recent work on the UPR mt in this setting.

What cost mitochondria? The maintenance of functional mitochondrial DNA within and across generations

PubMed Central

Aanen, Duur K.; Spelbrink, Johannes N.; Beekman, Madeleine

2014-01-01

The peculiar biology of mitochondrial DNA (mtDNA) potentially has detrimental consequences for organismal health and lifespan. Typically, eukaryotic cells contain multiple mitochondria, each with multiple mtDNA genomes. The high copy number of mtDNA implies that selection on mtDNA functionality is relaxed. Furthermore, because mtDNA replication is not strictly regulated, within-cell selection may favour mtDNA variants with a replication advantage, but a deleterious effect on cell fitness. The opportunities for selfish mtDNA mutations to spread are restricted by various organism-level adaptations, such as uniparental transmission, germline mtDNA bottlenecks, germline selection and, during somatic growth, regular alternation between fusion and fission of mitochondria. These mechanisms are all hypothesized to maintain functional mtDNA. However, the strength of selection for maintenance of functional mtDNA progressively declines with age, resulting in age-related diseases. Furthermore, organismal adaptations that most probably evolved to restrict the opportunities for selfish mtDNA create secondary problems. Owing to predominantly maternal mtDNA transmission, recombination among mtDNA from different individuals is highly restricted or absent, reducing the scope for repair. Moreover, maternal inheritance precludes selection against mtDNA variants with male-specific effects. We finish by discussing the consequences of life-history differences among taxa with respect to mtDNA evolution and make a case for the use of microorganisms to experimentally manipulate levels of selection. PMID:24864309

mtDNA lineage analysis of mouse L-cell lines reveals the accumulation of multiple mtDNA mutants and intermolecular recombination

PubMed Central

Fan, Weiwei; Lin, Chun Shi; Potluri, Prasanth; Procaccio, Vincent; Wallace, Douglas C.

2012-01-01

The role of mitochondrial DNA (mtDNA) mutations and mtDNA recombination in cancer cell proliferation and developmental biology remains controversial. While analyzing the mtDNAs of several mouse L cell lines, we discovered that every cell line harbored multiple mtDNA mutants. These included four missense mutations, two frameshift mutations, and one tRNA homopolymer expansion. The LA9 cell lines lacked wild-type mtDNAs but harbored a heteroplasmic mixture of mtDNAs, each with a different combination of these variants. We isolated each of the mtDNAs in a separate cybrid cell line. This permitted determination of the linkage phase of each mtDNA and its physiological characteristics. All of the polypeptide mutations inhibited their oxidative phosphorylation (OXPHOS) complexes. However, they also increased mitochondrial reactive oxygen species (ROS) production, and the level of ROS production was proportional to the cellular proliferation rate. By comparing the mtDNA haplotypes of the different cell lines, we were able to reconstruct the mtDNA mutational history of the L–L929 cell line. This revealed that every heteroplasmic L-cell line harbored a mtDNA that had been generated by intracellular mtDNA homologous recombination. Therefore, deleterious mtDNA mutations that increase ROS production can provide a proliferative advantage to cancer or stem cells, and optimal combinations of mutant loci can be generated through recombination. PMID:22345519

Pharmacological characterization of human recombinant melatonin mt1 and MT2 receptors

PubMed Central

Browning, Christopher; Beresford, Isabel; Fraser, Neil; Giles, Heather

2000-01-01

We have pharmacologically characterized recombinant human mt1 and MT2 receptors, stably expressed in Chinese hamster ovary cells (CHO-mt1 and CHO-MT2), by measurement of [3H]-melatonin binding and forskolin-stimulated cyclic AMP (cAMP) production. [3H]-melatonin bound to mt1 and MT2 receptors with pKD values of 9.89 and 9.56 and Bmax values of 1.20 and 0.82 pmol mg−1 protein, respectively. Whilst most melatonin receptor agonists had similar affinities for mt1 and MT2 receptors, a number of putative antagonists had substantially higher affinities for MT2 receptors, including luzindole (11 fold), GR128107 (23 fold) and 4-P-PDOT (61 fold). In both CHO-mt1 and CHO-MT2 cells, melatonin inhibited forskolin-stimulated accumulation of cyclic AMP in a concentration-dependent manner (pIC50 9.53 and 9.74, respectively) causing 83 and 64% inhibition of cyclic AMP production at 100 nM, respectively. The potencies of a range of melatonin receptor agonists were determined. At MT2 receptors, melatonin, 2-iodomelatonin and 6-chloromelatonin were essentially equipotent, whilst at the mt1 receptor these agonists gave the rank order of potency of 2-iodomelatonin>melatonin>6-chloromelatonin. In both CHO-mt1 and CHO-MT2 cells, melatonin-induced inhibition of forskolin-stimulated cyclic AMP production was antagonized in a concentration-dependent manner by the melatonin receptor antagonist luzindole, with pA2 values of 5.75 and 7.64, respectively. Melatonin-mediated responses were abolished by pre-treatment of cells with pertussis toxin, consistent with activation of Gi/Go G-proteins. This is the first report of the use of [3H]-melatonin for the characterization of recombinant mt1 and MT2 receptors. Our results demonstrate that these receptor subtypes have distinct pharmacological profiles. PMID:10696085

In vivo-folded metal-metallothionein 3 complexes reveal the Cu-thionein rather than Zn-thionein character of this brain-specific mammalian metallothionein.

PubMed

Artells, Ester; Palacios, Oscar; Capdevila, Mercè; Atrian, Sílvia

2014-03-01

Metallothionein-3 (MT3) is one of the four mammalian metallothioneins (MT), and is constitutively synthesized in the brain. MT3 acts both intracellularly and extracellularly in this organ, performing functions related to neuronal growth and physiological metal (Zn and Cu) handling. It appears to be involved in the prevention of neurodegenerative disorders caused by insoluble Cu-peptide aggregates, as it triggers a Zn-Cu swap that may counteract the deleterious presence of copper in neural tissues. The literature data on MT3 coordination come from studies either on apo-MT3 reconstitution or the reaction of Zn-MT3 with Cu(2+) , an ion that is hardly present inside cells. To ascertain the MT3 metal-binding features in a scenario closer to the reductive cell cytoplasm, a study of the recombinant Zn(2+) , Cd(2+) and Cu(+) complexes of MT3, βMT3, and αMT3, as well as the in vitro Zn(2+) -Cd(2+) and Zn(2+) -Cu(+) replacement processes, is presented here. We conclude that MT3 has a Cu-thionein character that is stronger than that of the MT1 and MT2 isoforms - also present in the mammalian brain - which is mainly contributed by its β domain. In contrast, the α domain retains a high capacity to bind Zn(2+) ions, and, consequently, the entire MT3 peptide shows a peculiar dual ability to handle both metal ions. The nature of the formed Cu(+) -MT3 complexes oscillates from heterometallic Cu6 Zn4 -MT3 to homometallic Cu10 -MT3 major species, in a narrow Cu concentration range. Therefore, the entire MT3 peptide shows a high capacity to bind Cu(+) , provided that this occurs in a nonoxidative milieux. This reflects a peculiar property of this MT isoform, which accurately senses different Cu contents in the environment in which it is synthesized. © 2014 FEBS.

The efficacy of manual therapy and exercise for treating non-specific neck pain: A systematic review

PubMed Central

Hidalgo, Benjamin; Hall, Toby; Bossert, Jean; Dugeny, Axel; Cagnie, Barbara; Pitance, Laurent

2017-01-01

OBJECTIVE: To review and update the evidence for different forms of manual therapy (MT) and exercise for patients with different stages of non-specific neck pain (NP). Data sources: MEDLINE, Cochrane-Register-of-Controlled-Trials, PEDro, EMBASE. METHOD: A qualitative systematic review covering a period from January 2000 to December 2015 was conducted according to updated-guidelines. Specific inclusion criteria only on RCTs were used; including differentiation according to stages of NP (acute – subacute [ASNP] or chronic [CNP]), as well as sub-classification based on type of MT interventions: MT1 (HVLA manipulation); MT2 (mobilization and/or soft-tissue-techniques); MT3 (MT1 + MT2); and MT4 (Mobilization-with-Movement). In each sub-category, MT could be combined or not with exercise and/or usual medical care. RESULTS: Initially 121 studies were identified for potential inclusion. Based on qualitative and quantitative evaluation criteria, 23 RCTs were identified for review. Evidence for ASNP: MODERATE-evidence: In favour of (i) MT1 to the cervical spine (Cx) combined with exercises when compared to MT1 to the thoracic spine (Tx) combined with exercises; (ii) MT3 to the Cx and Tx combined with exercise compared to MT2 to the Cx with exercise or compared to usual medical care for pain and satisfaction with care from short to long-term. Evidence for CNP: STRONG-evidence: Of no difference of efficacy between MT2 at the symptomatic Cx level(s) in comparison to MT2 on asymptomatic Cx level(s) for pain and function. MODERATE to STRONG-evidence: In favour of MT1 and MT3 on Cx and Tx with exercise in comparison to exercise or MT alone for pain, function, satisfaction with care and general-health from short to moderate-terms. MODERATE-evidence: In favour (i) of MT1 as compared to MT2 and MT4, all applied to the Cx, for neck mobility, and pain in the very short term; (ii) of MT2 using sof-tissue-techniques to the Cx and Tx or MT3 to the Cx and Tx in comparison to no-treatment in the short-term for pain and disability. CONCLUSION: This systematic review updates the evidence for MT combined or not with exercise and/or usual medical care for different stages of NP and provides recommendations for future studies. Two majors points could be highlighted, the first one is that combining different forms of MT with exercise is better than MT or exercise alone, and the second one is that mobilization need not be applied at the symptomatic level(s) for improvements of NP patients. These both points may have clinical implications for reducing the risk involved with some MT techniques applied to the cervical spine. PMID:28826164

The Development of Astronomy and Emergence of Astrophysics in New Zealand

NASA Astrophysics Data System (ADS)

Hearnshaw, John; Orchiston, Wayne

The development of astronomy and astrophysics in New Zealand from the earliest European exploration and settlement to the present day is discussed. The major contributions to astronomy by amateur astronomers are covered, as is the later development of astronomy and astrophysics in New Zealand's universities. The account includes the founding of professional observatories for optical astronomy at Mt. John (belonging to the University of Canterbury) and for radio astronomy at Warkworth (belonging to the Auckland University of Technology). Several major international collaborations in which New Zealand is participating (or has participated) are described, including SALT, MOA, IceCube and SKA. The founding and history of the Carter Observatory in Wellington, of the Stardome Observatory in Auckland (both engaged in astronomical education and outreach) and of the Royal Astronomical Society of New Zealand are briefly covered.

The Multipartite Mitochondrial Genome of Liposcelis bostrychophila: Insights into the Evolution of Mitochondrial Genomes in Bilateral Animals

PubMed Central

Yuan, Ming-Long; Dou, Wei; Barker, Stephen C.; Wang, Jin-Jun

2012-01-01

Booklice (order Psocoptera) in the genus Liposcelis are major pests to stored grains worldwide and are closely related to parasitic lice (order Phthiraptera). We sequenced the mitochondrial (mt) genome of Liposcelis bostrychophila and found that the typical single mt chromosome of bilateral animals has fragmented into and been replaced by two medium-sized chromosomes in this booklouse; each of these chromosomes has about half of the genes of the typical mt chromosome of bilateral animals. These mt chromosomes are 8,530 bp (mt chromosome I) and 7,933 bp (mt chromosome II) in size. Intriguingly, mt chromosome I is twice as abundant as chromosome II. It appears that the selection pressure for compact mt genomes in bilateral animals favors small mt chromosomes when small mt chromosomes co-exist with the typical large mt chromosomes. Thus, small mt chromosomes may have selective advantages over large mt chromosomes in bilateral animals. Phylogenetic analyses of mt genome sequences of Psocodea (i.e. Psocoptera plus Phthiraptera) indicate that: 1) the order Psocoptera (booklice and barklice) is paraphyletic; and 2) the order Phthiraptera (the parasitic lice) is monophyletic. Within parasitic lice, however, the suborder Ischnocera is paraphyletic; this differs from the traditional view that each suborder of parasitic lice is monophyletic. PMID:22479490

Parallel loss of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases and mtDNA-encoded tRNAs in Cnidaria.

PubMed

Haen, Karri M; Pett, Walker; Lavrov, Dennis V

2010-10-01

Unlike most animal mitochondrial (mt) genomes, which encode a set of 22 transfer RNAs (tRNAs) sufficient for mt protein synthesis, those of cnidarians have only retained one or two tRNA genes. Whether the missing cnidarian mt-tRNA genes relocated outside the main mt chromosome or were lost remains unclear. It is also unknown what impact the loss of tRNA genes had on other components of the mt translational machinery. Here, we explored the nuclear genome of the cnidarian Nematostella vectensis for the presence of mt-tRNA genes and their corresponding mt aminoacyl-tRNA synthetases (mt-aaRS). We detected no candidates for mt-tRNA genes and only two mt-aaRS orthologs. At the same time, we found that all but one cytosolic aaRS appear to be targeted to mitochondria. These results indicate that the loss of mt-tRNAs in Cnidaria is genuine and occurred in parallel with the loss of nuclear-encoded mt-aaRS. Our phylogenetic analyses of individual aaRS revealed that although the nearly total loss of mt-aaRS is rare, aaRS gene deletion and replacement have occurred throughout the evolution of Metazoa.

Potential role of alpha-synuclein and metallothionein in lead-induced inclusion body formation.

PubMed

Zuo, Peijun; Qu, Wei; Cooper, Ryan N; Goyer, Robert A; Diwan, Bhalchandra A; Waalkes, Michael P

2009-09-01

Lead (Pb) produces aggresome-like inclusion bodies (IBs) in target cells as a toxic response. Our prior work shows metallothionein (MT) is required for this process. We used MT-I/II double knockout (MT-null) and parental wild-type (WT) cell lines to further explore the formation process of Pb-induced IBs. Unlike WT cells, MT-null cells did not form IBs after Pb exposure. Western blot of cytosol showed soluble MT protein in WT cells was lost during Pb exposure as IBs formed. Transfection of MT-I into MT-null cells allowed IBs formation after Pb exposure. Considering Pb-induced IBs may be like disease-related aggresomes, which often contain alpha-synuclein (Scna), we investigated Scna expression in cells capable (WT) and incapable (MT-null) of producing IBs after Pb exposure. Scna protein showed poor basal expression in MT-null cells. Pb exposure increased Scna expression only in WT cells. MT transfection increased Scna transcript to WT levels. In WT or MT-transfected MT-null cells, Pb-induced Scna expression rapidly increased and then decreased over 48 h as Pb-induced IBs were formed. A direct interaction between Scna and MT was confirmed ex vivo by antibody pulldown assay where the proteins coprecipitated with an antibody to MT. Pb exposure caused increased colocalization of MT and Scna proteins with time only in WT cells. In WT mice after chronic Pb exposure Scna was localized in renal cells containing forming IBs, whereas MT-null mice did not form IBs. Thus, Scna could be component of Pb-induced IBs and, with MT, may play a role in IBs formation.

Mitochondrial ATPase Subunit 6 and Cytochrome B Gene Variations in Obese Turkish Children

PubMed Central

Demir, Durkadın; Türkkahraman, Doğa; Samur, Anıl Aktaş; Lüleci, Güven; Akçurin, Sema; M. Alper, Özgül

2014-01-01

Objective: Due to the importance of energy metabolism in mitochondria, mitochondrial genome variations are evaluated in energy-related diseases such as obesity. To date, several nuclear genes were found to be related to obesity. Our aim in this study was to investigate the presence of polymorphisms in mitochondrial ATPase subunit 6 (mt-ATP6) and cytochrome b (mt-CytB) genes that may be associated with childhood obesity. Methods: The mt-ATP6 and mt-CytB genes were amplified and entirely sequenced in a series of 100 obese and in an equal number of healthy Turkish children aged between 6-14 years. Results: A total of 118 synonymous and nonsynonymous variations were detected in the obese and control groups. Only two previously reported synonymous substitutions (mt.8614T>C and mt.8994G>A) in the mt-ATP6 gene were found to be significantly higher in the obese group compared to the control group (p<0.05). In the mt-ATP6 gene, one novel nonsynonymous substitution (mt.8726C>T) and one novel synonymous substitution (mt.9108A>T) were found. In the mt-CytB gene, one nonsynonymous substitution (mt.14880T>C) and two synonymous substitutions (mt.14891C>T and mt.15091C>T) were novel substitutions. Conclusion: Two synonymous substitutions (mt.8614T>C and mt.8994G>A) in the mt-ATP6 gene may be associated with childhood obesity. Our study provides the first data about mitochondrial genome variations in a Turkish obese population and also the first in obese children. More cases should be screened in obese groups in order to understand the effects of mitochondrial polymorphisms in the development of obesity. PMID:25541891

Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, Yuhui; Huang, Jiawei; Gu, Ying

Depleted uranium (DU) has been widely used in both civilian and military activities, and the kidney is the main target organ of DU during acute high-dose exposures. In this study, the nephrotoxicity caused by DU in metallothionein-1/2-null mice (MT −/−) and corresponding wild-type (MT +/+) mice was investigated to determine any associations with MT. Each MT −/− or MT +/+ mouse was pretreated with a single dose of DU (10 mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4 days of DU administration, kidney changes were assessed. After DU exposure, serum creatinine and serum urea nitrogen in MTmore » −/− mice significantly increased than in MT +/+ mice, with more severe kidney pathological damage. Moreover, catalase and superoxide dismutase (SOD) decreased, and generation of reactive oxygen species and malondialdehyde increased in MT −/− mice. The apoptosis rate in MT −/− mice significantly increased, with a significant increase in both Bax and caspase 3 and a decrease in Bcl-2. Furthermore, sodium-glucose cotransporter (SGLT) and sodium-phosphate cotransporter (NaPi-II) were significantly reduced after DU exposure, and the change of SGLT was more evident in MT −/− mice. Finally, exogenous MT was used to evaluate the correlation between kidney changes induced by DU and MT doses in MT −/− mice. The results showed that, the pathological damage and cell apoptosis decreased, and SOD and SGLT levels increased with increasing dose of MT. In conclusion, MT deficiency aggravated DU-induced nephrotoxicity, and the molecular mechanisms appeared to be related to the increased oxidative stress and apoptosis, and decreased SGLT expression. - Highlights: • MT −/− and MT +/+ mice were used to evaluate nephrotoxicity of DU. • Renal damage was more evident in the MT −/− mice after exposure to DU. • Exogenous MT also protects against DU-induced nephrotoxicity. • MT deficiency induced more ROS and apoptosis after exposure to DU. • MT deficiency down-regulated SGLT expression after exposure to DU.« less

A Reduced Number of mtSNPs Saturates Mitochondrial DNA Haplotype Diversity of Worldwide Population Groups

PubMed Central

Salas, Antonio; Amigo, Jorge

2010-01-01

Background The high levels of variation characterising the mitochondrial DNA (mtDNA) molecule are due ultimately to its high average mutation rate; moreover, mtDNA variation is deeply structured in different populations and ethnic groups. There is growing interest in selecting a reduced number of mtDNA single nucleotide polymorphisms (mtSNPs) that account for the maximum level of discrimination power in a given population. Applications of the selected mtSNP panel range from anthropologic and medical studies to forensic genetic casework. Methodology/Principal Findings This study proposes a new simulation-based method that explores the ability of different mtSNP panels to yield the maximum levels of discrimination power. The method explores subsets of mtSNPs of different sizes randomly chosen from a preselected panel of mtSNPs based on frequency. More than 2,000 complete genomes representing three main continental human population groups (Africa, Europe, and Asia) and two admixed populations (“African-Americans” and “Hispanics”) were collected from GenBank and the literature, and were used as training sets. Haplotype diversity was measured for each combination of mtSNP and compared with existing mtSNP panels available in the literature. The data indicates that only a reduced number of mtSNPs ranging from six to 22 are needed to account for 95% of the maximum haplotype diversity of a given population sample. However, only a small proportion of the best mtSNPs are shared between populations, indicating that there is not a perfect set of “universal” mtSNPs suitable for all population contexts. The discrimination power provided by these mtSNPs is much higher than the power of the mtSNP panels proposed in the literature to date. Some mtSNP combinations also yield high diversity values in admixed populations. Conclusions/Significance The proposed computational approach for exploring combinations of mtSNPs that optimise the discrimination power of a given set of mtSNPs is more efficient than previous empirical approaches. In contrast to precedent findings, the results seem to indicate that only few mtSNPs are needed to reach high levels of discrimination power in a population, independently of its ancestral background. PMID:20454657

Drosophila nuclear factor DREF regulates the expression of the mitochondrial DNA helicase and mitochondrial transcription factor B2 but not the mitochondrial translation factor B1

PubMed Central

Fernández-Moreno, Miguel A.; Hernández, Rosana; Adán, Cristina; Roberti, Marina; Bruni, Francesco; Polosa, Paola Loguercio; Cantatore, Palmiro; Matsushima, Yuichi; Kaguni, Laurie S.; Garesse, Rafael

2016-01-01

DREF [DRE (DNA replication-related element)-binding factor] controls the transcription of numerous genes in Drosophila, many involved in nuclear DNA (nDNA) replication and cell proliferation, three in mitochondrial DNA (mtDNA) replication and two in mtDNA transcription termination. In this work, we have analysed the involvement of DREF in the expression of the known remaining genes engaged in the minimal mtDNA replication (d-mtDNA helicase) and transcription (the activator d-mtTFB2) machineries and of a gene involved in mitochondrial mRNA translation (d-mtTFB1). We have identified their transcriptional initiation sites and DRE sequences in their promoter regions. Gel-shift and chromatin immunoprecipitation assays demonstrate that DREF interacts in vitro and in vivo with the d-mtDNA helicase and d-mtTFB2, but not with the d-mtTFB1 promoters. Transient transfection assays in Drosophila S2 cells with mutated DRE motifs and truncated promoter regions show that DREF controls the transcription of d-mtDNA helicase and d-mtTFB2, but not that of d-mtTFB1. RNA interference of DREF in S2 cells reinforces these results showing a decrease in the mRNA levels of d-mtDNA helicase and d-mtTFB2 and no changes in those of the d-mtTFB1. These results link the genetic regulation of nuclear DNA replication with the genetic control of mtDNA replication and transcriptional activation in Drosophila. PMID:23916463

mtDNA recombination in a natural population.

PubMed

Saville, B J; Kohli, Y; Anderson, J B

1998-02-03

Variation in mtDNA has been used extensively to draw inferences in phylogenetics and population biology. In the majority of eukaryotes investigated, transmission of mtDNA is uniparental and clonal, with genotypic diversity arising from mutation alone. In other eukaryotes, the transmission of mtDNA is biparental or primarily uniparental with the possibility of "leakage" from the minority parent. In these cases, heteroplasmy carries the potential for recombination between mtDNAs of different descent. In fungi, such mtDNA recombination has long been documented but only in laboratory experiments and only under conditions in which heteroplasmy is ensured. Despite this experimental evidence, mtDNA recombination has not been to our knowledge documented in a natural population. Because evidence from natural populations is prerequisite to understanding the evolutionary impact of mtDNA recombination, we investigated the possibility of mtDNA recombination in an organism with the demonstrated potential for heteroplasmy in laboratory matings. Using nucleotide sequence data, we report here that the genotypic structure of mtDNA in a natural population of the basidiomycete fungus Armillaria gallica is inconsistent with purely clonal mtDNA evolution and is fully consistent with mtDNA recombination.

Characterization and expression of a metallothionein gene in the aquatic fern Azolla filiculoides under heavy metal stress.

PubMed

Schor-Fumbarov, Tamar; Goldsbrough, Peter B; Adam, Zach; Tel-Or, Elisha

2005-12-01

A cDNA encoding a type 2 metallothionein (MT) was isolated from Azolla filiculoides, termed AzMT2, accession no. AF482470. The AzMT2 transcript was expressed in sterile A. filiculoides that were free of the cyanobiont Anabaena azollae after erythromycin treatment, proving that AzMT2 is encoded by the fern genome. AzMT2 RNA expression was enhanced by the addition of Cd(+2), Cu(+2), Zn(+2) and Ni(+2) to the growth medium. The transcript level of AzMT2 correlated with the metal content in the plants. Temporal analysis of AzMT2 expression demonstrated that Cd(2+) and Ni(2+) induction of AzMT2 RNA expression occurred within 48 h. AzMT2-enhanced expression responded more intensely to the toxic Cd and Ni ions in A. filiculoides suggesting that AzMT2 may participate in detoxification mechanism. The more moderate response of AzMT2 to Zn and Cu ions, which are essential micronutrients, suggest a role for AzMT2 in metal homeostasis.

Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.

We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% andmore » 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.« less

Nuclear and mitochondrial patterns of population structure in North Pacific false killer whales (Pseudorca crassidens).

PubMed

Martien, Karen K; Chivers, Susan J; Baird, Robin W; Archer, Frederick I; Gorgone, Antoinette M; Hancock-Hanser, Brittany L; Mattila, David; McSweeney, Daniel J; Oleson, Erin M; Palmer, Carol; Pease, Victoria L; Robertson, Kelly M; Schorr, Gregory S; Schultz, Mark B; Webster, Daniel L; Taylor, Barbara L

2014-01-01

False killer whales (Pseudorca crassidens) are large delphinids typically found in deep water far offshore. However, in the Hawaiian Archipelago, there are 2 resident island-associated populations of false killer whales, one in the waters around the main Hawaiian Islands (MHI) and one in the waters around the Northwestern Hawaiian Islands (NWHI). We use mitochondrial DNA (mtDNA) control region sequences and genotypes from 16 nuclear DNA (nucDNA) microsatellite loci from 206 individuals to examine levels of differentiation among the 2 island-associated populations and offshore animals from the central and eastern North Pacific. Both mtDNA and nucDNA exhibit highly significant differentiation between populations, confirming limited gene flow in both sexes. The mtDNA haplotypes exhibit a strong pattern of phylogeographic concordance, with island-associated populations sharing 3 closely related haplotypes not found elsewhere in the Pacific. However, nucDNA data suggest that NWHI animals are at least as differentiated from MHI animals as they are from offshore animals. The patterns of differentiation revealed by the 2 marker types suggest that the island-associated false killer whale populations likely share a common colonization history, but have limited contemporary gene flow. Published by Oxford University Press on behalf of the American Genetic Association 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

On the Existence of the Logarithmic Surface Layer in the Inner Core of Hurricanes

DTIC Science & Technology

2012-01-01

characteristics of eyewall boundary layer of Hurricane Hugo (1989). Mon. Wea. Rev., 139, 1447-1462. Zhang, JA, Montgomery MT. 2012 Observational...the inner core of hurricanes Roger K. Smitha ∗and Michael T. Montgomeryb a Meteorological Institute, University of Munich, Munich, Germany b Dept. of...logarithmic surface layer”, or log layer, in the boundary layer of the rapidly-rotating core of a hurricane . One such study argues that boundary-layer

Implementation Guidance for the Accelerated Improvement Method (AIM). Software Engineering Process Management: Special Report

DTIC Science & Technology

2010-12-01

PSP and TSP books by Watts Humphrey or in the TSP-MT (multi-team) process extension. A few additional items should be created, e.g., see OPD-2...Institute, Carnegie Mellon University, 2000. www.sei.cmu.edu/library/abstracts/reports/00tr023.cfm [ Humphrey 2005] Humphrey , Watts S . PSP : A Self... Humphrey 2006] Humphrey , Watts S . TSP: Coaching Development Teams. Addison Wesley, 2006 (ISBN 978- 0201731132). www.sei.cmu.edu/library/abstracts/

Pathogenic role of mtDNA duplications in mitochondrial diseases associated with mtDNA deletions.

PubMed

Odoardi, Francesca; Rana, Michele; Broccolini, Aldobrando; Mirabella, Massimiliano; Modoni, Anna; D'Amico, Adele; Papacci, Manuela; Tonali, Pietro; Servidei, Serenella; Silvestri, Gabriella

2003-04-30

We estimated the frequency of multiple mtDNA rearrangements by Southern blot in 32 patients affected by mitochondrial disorders associated with single deletions in order to assess genotype-phenotype correlations and elucidate the pathogenic significance of mtDNA duplications. Muscle in situ hybridization studies were performed in patients showing mtDNA duplications at Southern blot. We found multiple rearrangements in 12/32 (37.5%) patients; in particular, mtDNA duplications were detected in 4/4 Kearns-Sayre syndrome (KSS), in 1 Pearson's syndrome, in 1/3 encephalomyopathies with progressive external ophthalmoplegia (PEO), and in 2/23 PEO. In situ studies documented an exclusive accumulation of deleted mtDNAs in cytochrome c oxidase negative fibers of patients with mtDNA duplications. The presence of mtDNA duplications significantly correlated with onset of symptoms before age 15 and occurrence of clinical multisystem involvement. Analysis of biochemical data documented a predominant reduction of complex III in patients without duplications compared to patients with mtDNA duplications. Our data indicate that multiple mtDNA rearrangements are detectable in a considerable proportion of patients with single deletions and that mtDNA duplications do not cause any oxidative impairment. They more likely play a pathogenic role in the determination of clinical expression of mitochondrial diseases associated with single mtDNA deletions, possibly generating deleted mtDNAs in embryonic tissues by homologous recombination. Copyright 2003 Wiley-Liss, Inc.

Using hyperspectral plant signatures for CO2 leak detection during the 2008 ZERT CO2 sequestration field experiment in Bozeman, Montana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Male, E.J.; Pickles, W.L.; Silver, E.A.

2009-11-01

Hyperspectral plant signatures can be used as a short-term, as well as long-term (100-yr timescale) monitoring technique to verify that CO2 sequestration fields have not been compromised. An influx of CO2 gas into the soil can stress vegetation, which causes changes in the visible to nearinfrared reflectance spectral signature of the vegetation. For 29 days, beginning on July 9th, 2008, pure carbon dioxide gas was released through a 100-meter long horizontal injection well, at a flow rate of 300 kg/day. Spectral signatures were recorded almost daily from an unmown patch of plants over the injection with a ''FieldSpec Pro'' spectrometermore » by Analytical Spectral Devices, Inc. Measurements were taken both inside and outside of the CO2 leak zone to normalize observations for other environmental factors affecting the plants.« less

Aberration of mitosis by hexavalent chromium in some Fabaceae members is mediated by species-specific microtubule disruption.

PubMed

Eleftheriou, Eleftherios P; Michalopoulou, Vasiliki A; Adamakis, Ioannis-Dimosthenis S

2015-05-01

Because the detrimental effects of chromium (Cr) to higher plants have been poorly investigated, the present study was undertaken to verify the toxic attributes of hexavalent chromium [Cr(VI)] to plant mitotic microtubules (MTs), to determine any differential disruption of MTs during mitosis of taxonomically related species and to clarify the relationship between the visualized chromosomal aberrations and the Cr(VI)-induced MT disturbance. For this purpose, 5-day-old uniform seedlings of Vicia faba, Pisum sativum, Vigna sinensis and Vigna angularis, all belonging to the Fabaceae family, were exposed to 250 μM Cr(VI) supplied as potassium dichromate (K₂Cr₂O₇) for 24, 72 and 120 h and others in distilled water serving as controls. Root tip samples were processed for tubulin immunolabelling (for MT visualization) and DNA fluorescent staining (for chromosomal visualization). Microscopic preparations of cell squashes were then examined and photographed by confocal laser scanning microscopy (CLSM). Cr(VI) halted seedling growth turning roots brown and necrotic. Severe chromosomal abnormalities and differential disturbance of the corresponding MT arrays were found in all mitotic phases. In particular, in V. faba MTs were primarily depolymerized and replaced by atypical tubulin conformations, whereas in P. sativum, V. sinensis and V. angularis they became bundled in a time-dependent manner. In P. sativum, the effects were milder compared to those of the other species, but in all cases MT disturbance adversely affected the proper aggregation of chromosomes on the metaphase plate, their segregation at anaphase and organization of the new nuclei at telophase. Cr(VI) is very toxic to seedling growth. The particular effect depends on the exact stage the cell is found at the time of Cr(VI) entrance and is species-specific. Mitotic MT arrays are differentially deranged by Cr(VI) in the different species examined, even if they are taxonomically related, while their disturbance underlies chromosomal abnormalities. Results furthermore support the view that MTs may constitute a reliable, sensitive and universal subcellular marker for monitoring heavy metal toxicity.

Mount Everest (Chomolungma, Goddess Mother of the World)

NASA Technical Reports Server (NTRS)

2002-01-01

Mt. Everest is the highest (29,035 feet, 8850 meters) mountain in the world. This detailed look at Mt. Everest and Lhotse is part of a more extensive photograph of the central Himalaya taken in October 1993 that is one of the best views of the mountain captured by astronauts to date. It shows the North and South Faces of Everest in shadow with the Kangshung Face in morning light. Other major peaks in the immediate area are Nuptse and Bei Peak (Changtse). The picture was taken looking slightly obliquely when the spacecraft was north of Everest. Everest holds a powerful fascination for climbers and trekkers from around the world. The paths for typical North and South climbing routes are sketched on this image. Much of the regional context can be seen in the complete photograph, which shows Mt. Everest and other large peaks to the northwest. More information on the photograph STS058-101-12 can be found at the Gateway to Astronaut Photography of Earth. An unannotated version can also be downloaded. The digital images shown have been reduced to a spatial resolution equivalent to 48 m / pixel; a high-resolution digital image of the same photograph would be at 12 meters per pixel. A new interactive tutorial, Find Mt. Everest From Space, is now available on the Web. The presentation was created by the Earth Sciences and Image Analysis Laboratory, Johnson Space Center, from astronaut training materials developed by William R. Muehlberger (University of Texas, Austin), who has instructed astronauts in geology since the Apollo missions. While circling the globe every 90 minutes, astronauts have only seconds to find key peaks in the Himalayas. These photographs are used to train their eyes so they can rapidly find and photograph Everest when they pass over. The tutorial features astronaut photographs of the Himalayas, interactive graphics that illustrate key geographic features for locating Mt. Everest, and. information on the geology of the region. The lesson concludes with a test of your ability to identify Everest in different photographs taken from the Space Shuttle. Earth Sciences and Image Analysis Laboratory, Johnson Space Center

Adjusting MtDNA Quantification in Whole Blood for Peripheral Blood Platelet and Leukocyte Counts.

PubMed

Hurtado-Roca, Yamilee; Ledesma, Marta; Gonzalez-Lazaro, Monica; Moreno-Loshuertos, Raquel; Fernandez-Silva, Patricio; Enriquez, Jose Antonio; Laclaustra, Martin

2016-01-01

Alterations of mitochondrial DNA copy number (mtDNAcn) in the blood (mitochondrial to nuclear DNA ratio) appear associated with several systemic diseases, including primary mitochondrial disorders, carcinogenesis, and hematologic diseases. Measuring mtDNAcn in DNA extracted from whole blood (WB) instead of from peripheral blood mononuclear cells or buffy coat may yield different results due to mitochondrial DNA present in platelets. The aim of this work is to quantify the contribution of platelets to mtDNAcn in whole blood [mtDNAcn(WB)] and to propose a correction formula to estimate leukocytes' mtDNAcn [mtDNAcn(L)] from mtDNAcn(WB). Blood samples from 10 healthy adults were combined with platelet-enriched plasma and saline solution to produce artificial blood preparations. Aliquots of each sample were combined with five different platelet concentrations. In 46 of these blood preparations, mtDNAcn was measured by qPCR. MtDNAcn(WB) increased 1.07 (95%CI 0.86, 1.29; p<0.001) per 1000 platelets present in the preparation. We proved that leukocyte count should also be taken into account as mtDNAcn(WB) was inversely associated with leukocyte count; it increased 1.10 (95%CI 0.95, 1.25, p<0.001) per unit increase of the ratio between platelet and leukocyte counts. If hematological measurements are available, subtracting 1.10 the platelets/leukocyte ratio from mtDNAcn(WB) may serve as an estimation for mtDNAcn(L). Both platelet and leukocyte counts in the sample are important sources of variation if comparing mtDNAcn among groups of patients when mtDNAcn is measured in DNA extracted from whole blood. Not taking the platelet/leukocyte ratio into account in whole blood measurements, may lead to overestimation and misclassification if interpreted as leukocytes' mtDNAcn.

Feasibility study of a combined treatment of electromyography-triggered neuromuscular stimulation and mirror therapy in stroke patients: a randomized crossover trial.

PubMed

Kojima, Kosuke; Ikuno, Koki; Morii, Yuta; Tokuhisa, Kentaro; Morimoto, Shigeru; Shomoto, Koji

2014-01-01

Mirror therapy (MT) and electromyography-triggered neuromuscular stimulation (ETMS) are both effective treatments for impaired upper limbs following stroke. A combination of these two treatments (ETMS-MT) may result in greater gain than either treatment alone. The feasibility and possible effects of ETMS-MT upon upper extremity function were investigated in stroke patients. Thirteen post-acute stroke patients were randomly assigned to an immediate ETMS-MT group or a delayed ETMS-MT group and then underwent an 8-week training program. The immediate ETMS-MT group received ETMS-MT in addition to physical and occupational therapy (PT+OT) for 4 weeks. They then received only PT+OT for the next 4 weeks. In the delayed ETMS-MT group, interventions were provided in the reverse order. The main outcome measure was the Fugl-Meyer Assessment (FMA). The immediate ETMS-MT group showed significantly greater gain in FMA in the first 4 weeks. The delayed ETMS-MT group showed significantly greater gain in active range of motion during the latter 4 weeks. No adverse effects were reported following ETMS-MT. ETMS-MT might be as effective as independent MT or ETMS without causing any side effects. Future research should focus upon the direct comparisons between independent and combined interventions.

Genome sequence of two members of the chloroaromatic-degrading MT community: Pseudomonas reinekei MT1 and Achromobacter xylosoxidans MT3.

PubMed

Gutierrez-Urrutia, Izabook; Miossec, Matthieu J; Valenzuela, Sandro L; Meneses, Claudio; Dos Santos, Vitor A P Martins; Castro-Nallar, Eduardo; Poblete-Castro, Ignacio

2018-06-10

We describe the genome sequence of Pseudomonas reinekei MT1 and Achromobacter xylosoxidans MT3, the most abundant members of a bacterial community capable of degrading chloroaromatic compounds. The MT1 genome contains open reading frames encoding enzymes responsible for the catabolism of chlorosalicylate, methylsalicylate, chlorophenols, phenol, benzoate, p-coumarate, phenylalanine, and phenylacetate. On the other hand, the MT3 strain genome possesses no ORFs to metabolize chlorosalicylates; instead the bacterium is capable of metabolizing nitro-phenolic and phenolic compounds, which can be used as the only carbon and energy source by MT3. We also confirmed that MT3 displays the genetic machinery for the metabolism of chlorocathecols and chloromuconates, where the latter are toxic compounds secreted by MT1 when degrading chlorosalicylates. Altogether, this work will advance our fundamental understanding of bacterial interactions. Copyright © 2018 Elsevier B.V. All rights reserved.

The Effect of Microgravity on the Smallest Space Travelers: Bacterial Physiology and Virulence on Earth and in Microgravity

NASA Technical Reports Server (NTRS)

Pyle, Barry; Vasques, Marilyn; Aquilina, Rudy (Technical Monitor)

2002-01-01

Since the first human flights outside of Earth's gravity, crew health and well-being have been major concerns. Exposure to microgravity during spaceflight is known to affect the human immune response, possibly making the crew members more vulnerable to infectious disease. In addition, biological experiments previously flown in space have shown that bacteria grow faster in microgravity than they do on Earth. The ability of certain antibiotics to control bacterial infections may also differ greatly in microgravity. It is therefore critical to understand how spaceflight and microgravity affect bacterial virulence, which is their ability to cause disease. By utilizing spaceflight hardware provided by the European Space Agency (ESA), Dr. Barry Pyle and his team at Montana State University, Bozeman, will be performing an experiment to study the effects of microgravity on the virulence of a common soil and water bacterium, Pseudomonas aeruginosa. Importantly, these bacteria have been detected in the water supplies of previous Space Shuttle flights. The experiment will examine the effects of microgravity exposure on bacterial growth and on the bacterium's ability to form a toxin called Exotoxin A. Another goal is to evaluate the effects of microgravity on the physiology of the bacteria by analyzing their ability to respire (produce energy), by studying the condition of the plasma membrane surrounding the cell, and by determining if specific enzymes remain active. Proteins produced by the bacteria will also be assayed to see if the normal functions of the bacteria are affected. In the context of human life support in spaceflight, the results of this experiment will offer guidance in providing the highest possible water quality for the Shuttle in order to limit the risk of infection to human occupants and to minimize water system and spacecraft deterioration.

Transient Changes in Shallow Groundwater Chemistry During the MSU-ZERT CO2 Injection Experiment

NASA Astrophysics Data System (ADS)

Zheng, L.; Apps, J. A.; Spycher, N.; Birkholzer, J. T.; Kharaka, Y. K.; Thordsen, J. J.; Kakouros, E.; Trautz, R. C.

2009-12-01

The Montana State University Zero Emission Research and Technology (MSU-ZERT) field experiment at Bozeman, Montana, is designed to evaluate atmospheric and near-surface monitoring and detection techniques applicable to the potential leakage of CO2 from deep storage reservoirs. However, the experiment also affords an excellent opportunity to investigate the transient changes in groundwater chemical composition in response to increasing CO2 partial pressures. Between July 9 and August 7, 2008, 300 kg/day of food-grade CO2 was injected into shallow groundwater through a horizontal perforated pipe about 2-2.3 m below the ground surface. Changes in groundwater quality were investigated through comprehensive chemical analyses of 80 water samples taken before, during and following CO2 injection from 10 shallow observation wells located 1-6 m from the injection pipe, and from two distant monitoring wells. Field and laboratory analyses suggest rapid and systematic changes in pH, alkalinity, and conductance, as well as increases in the aqueous concentrations of both major and trace element species. A principal component analysis and independent thermodynamic interpretation of the water quality analyses were conducted. Results were interpreted in conjunction with a mineralogical characterization of the shallow sediments and a review of historical records of the chemical composition of rainfall at neighboring monitoring sites. The interpretation permitted tentative identification of a complex array of adsorption/desorption, ion exchange, precipitation/dissolution, oxidation/reduction and infiltration processes that were operative during the test. Geochemical modeling was conducted using TOUGHREACT to test whether the observed water quality changes were consistent with the hypothesized processes, and very good agreement was obtained with respect to the behavior of both major and trace elements.

Combining afferent stimulation and mirror therapy for rehabilitating motor function, motor control, ambulation, and daily functions after stroke.

PubMed

Lin, Keh-chung; Huang, Pai-chuan; Chen, Yu-ting; Wu, Ching-yi; Huang, Wen-ling

2014-02-01

Mirror therapy (MT) and mesh glove (MG) afferent stimulation may be effective in reducing motor impairment after stroke. A hybrid intervention of MT combined with MG (MT + MG) may broaden aspects of treatment benefits. To demonstrate the comparative effects of MG + MT, MT, and a control treatment (CT) on the outcomes of motor impairments, manual dexterity, ambulation function, motor control, and daily function. Forty-three chronic stroke patients with mild to moderate upper extremity impairment were randomly assigned to receive MT + MG, MT, or CT for 1.5 hours/day, 5 days/week for 4 weeks. Outcome measures were the Fugl-Meyer Assessment (FMA) and muscle tone measured by Myoton-3 for motor impairment and the Box and Block Test (BBT) and 10-Meter Walk Test (10 MWT) for motor function. Secondary outcomes included kinematic parameters for motor control and the Motor Activity Log and ABILHAND Questionnaire for daily function. FMA total scores were significantly higher and synergistic shoulder abduction during reach was less in the MT + MG and MT groups compared with the CT group. Performance on the BBT and the 10 MWT (velocity and stride length in self-paced task and velocity in as-quickly-as-possible task) were improved after MT + MG compared with MT. MT + MG improved manual dexterity and ambulation. MT + MG and MT reduced motor impairment and synergistic shoulder abduction more than CT. Future studies may integrate functional task practice into treatments to enhance functional outcomes in patients with various levels of motor severity. The long-term effects of MG + MT remain to be evaluated.

OCCUPATIONAL EXPOSURE OF NMR SPECTROMETRISTS TO STATIC AND RADIOFREQUENCY FIELDS.

PubMed

Berlana, Tania; Úbeda, Alejandro

2017-12-01

Occupational exposure to static and radiofrequency fields emitted by nuclear magnetic resonance spectrometers was assessed through systematic field metering during operation of 19 devices in nine research centers. Whereas no measurable levels of radiofrequency radiation were registered outside the spectrometers, significant exposure to static field was detected, with maximum values recorded at the user's hand (B = 683.00 mT) and head-thorax (B = 135.70 mT) during spectrometer manipulation. All values were well below the exposure limits set by the European standard for workers protection against the effects of acute field exposure only. As for potential effects of chronic exposure, waiting for more complete knowledge, adoption of technical and operational strategies for exposure minimizing is advisable. In this respect, the data revealed that compared with standard magnetic shielding, ultrashield technology allows a 20-65-fold reduction of the field strength received by the operator. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Snake River Plain FORGE Site Characterization Data

DOE Data Explorer

Moos, Danial; Barton, Colleen A.

2016-04-18

The site characterization data used to develop the conceptual geologic model for the Snake River Plain site in Idaho, as part of phase 1 of the Frontier Observatory for Research in Geothermal Energy (FORGE) initiative. This collection includes data on seismic events, groundwater, geomechanical models, gravity surveys, magnetics, resistivity, magnetotellurics (MT), rock physics, stress, the geologic setting, and supporting documentation, including several papers. Also included are 3D models (Petrel and Jewelsuite) of the proposed site. Data for wells INEL-1, WO-2, and USGS-142 have been included as links to separate data collections. These data have been assembled by the Snake River Geothermal Consortium (SRGC), a team of collaborators that includes members from national laboratories, universities, industry, and federal agencies, lead by the Idaho National Laboratory (INL). Other contributors include the National Renewable Energy Laboratory (NREL), Lawrence Livermore National Laboratory (LLNL), the Center for Advanced Energy Studies (CEAS), the University of Idaho, Idaho State University, Boise State University, University of Wyoming, University of Oklahoma, Energy and Geoscience Institute-University of Utah, US Geothermal, Baker Hughes Campbell Scientific Inc., Chena Power, US Geological Survey (USGS), Idaho Department of Water Resources, Idaho Geological Survey, and Mink GeoHydro.

Metallothionein turnover in mammalian cell lines: implications in drug resistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monia, B.P.; Butt, T.R.; Ecker, D.J.

1986-05-01

Metallothioneins (MT) are low molecular weight, cysteine-rich proteins believed to participate in metal detoxification. A wide variety of cells in culture have been shown to accumulate MT in response to metal administration. These metal-induced increases in MT levels result from an increased rate of MT gene transcription, MT mRNA accumulation, and MT synthesis. Turnover of Cd-, Zn- and Au-induced MT was studied in a Chinese Hamster Ovary (CHO) cell line which was resistant to Cd and the Au-containing drug Auranofin (AF). Cd, Zn and Au were potent inducers of MT mRNA and accumulated approximately equal amounts of mRNA under themore » conditions employed in this study. Pulse-chase studies utilizing (/sup 35/S)cysteine revealed that the half-life of Au-, Zn- and Cd-induced MT was 0.75, 10 and 24 hrs. respectively. The reported differences in the tertiary structure of Au-MT from that of Cd-MT lead us to propose that the differences in half-lives observed reflect differences in subceptibility to intracellular proteolysis, which in turn, may effect the ability of MT to confer resistance to various metals.« less

Multi scale modeling of 2450MHz electric field effects on microtubule mechanical properties.

PubMed

Setayandeh, S S; Lohrasebi, A

2016-11-01

Microtubule (MT) rigidity and response to 2450MHz electric fields were investigated, via multi scale modeling approach. For this purpose, six systems were designed and simulated to consider all types of feasible interactions between α and β monomers in MT, by using all atom molecular dynamics method. Subsequently, coarse grain modeling was used to design different lengths of MT. Investigation of effects of external 2450MHz electric field on MT showed MT less rigidity in the presence of such field, which may perturb its functions. Moreover, an additional computational setup was designed to study effects of 2450MHz field on MT response to AFM tip. It was found, more tip velocity led to MT faster transformation and less time was required to change MT elastic response to plastic one, applying constant radius. Moreover it was observed smaller tip caused to increase required time to change MT elastic response to plastic one, considering constant velocity. Furthermore, exposing MT to 2450MHz field led to no significant changes in MT response to AFM tip, but quick change in MT elastic response to plastic one. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluating use and outcomes of mobility technology: a multiple stakeholder analysis.

PubMed

Hammel, Joy; Southall, Kenneth; Jutai, Jeffrey; Finlayson, Marcia; Kashindi, Gabriel; Fok, Daniel

2013-07-01

This qualitative, multi-site study compared and contrasted the outcomes of mobility technology (MT) and the factors influencing these outcomes from the perspective of MT users, caregivers, and professionals involved in MT service delivery. Qualitative focus groups were held in the USA and Canada with multiple stakeholder groups (consumer: n = 45, caregiver: n = 10, service provider: n = 10). Data were analyzed thematically. MT outcomes were conceptualized by participants as a match between expectations for MT and the actual outcomes experienced. Several factors influenced the match including a) MT features, b) environmental factors (e.g. built/physical environment, societal context of acceptance, MT delivery systems/policies), and c) the ability to self-manage the interaction across person, technology and environment, which involved constant negotiation and strategizing. Stakeholders identified MT outcomes that corresponded to ICF levels including body structure and function, activity, and participation across environments; however, varied on their importance and influence on MT impact. The conceptual fit model and factors related to self-management of MT represent new knowledge and provide a framework for stakeholder-based evaluation of MT outcomes. Implications for MT assessment, service delivery, outcomes research, and interventions are discussed.

Deoxynucleoside salvage enzymes and tissue specific mitochondrial DNA depletion.

PubMed

Wang, L

2010-06-01

Adequate mitochondrial DNA (mtDNA) copies are required for normal mitochondria function and reductions in mtDNA copy number due to genetic alterations cause tissue-specific mtDNA depletion syndrome (MDS). There are eight nuclear genes, directly or indirectly involved in mtDNA replication and mtDNA precursor synthesis, which have been identified as the cause of MDS. However, the tissue specific pathology of these nuclear gene mutations is not well understood. Here, mtDNA synthesis, mtDNA copy number control, and mtDNA turnover, as well as the synthesis of mtDNA precursors in relation to the levels of salvage enzymes are discussed. The question why MDS caused by TK2 and p53R2 mutations are predominantly muscle specific while dGK deficiency affected mainly liver will be addressed.

MESSENGER Education and Public Outreach Arranges a Ride to the Innermost Planet

NASA Astrophysics Data System (ADS)

Weir, H. M.; Chapman, C. R.; Edmonds, J.; Goldstein, J.; Hallau, K. G.; Hirshon, B.; Vanhala, H.; Solomon, S. C.; Messenger Education; Public Outreach Team

2010-12-01

Exploration of the mysterious planet Mercury offers an unprecedented opportunity for teachers, students, and citizens to tag along for the ride, and the Education and Public Outreach (EPO) Team for MESSENGER (MErcury Surface, Space ENvironment, GEochemistry, and Ranging) is making sure the public gets quite a show. Since 2004, when MESSENGER was launched, MESSENGER has been gathering intriguing data and information about the Solar System's innermost planet. That journey will continue at a quickened pace after March 18, 2011, when MESSENGER enters into orbit around Mercury for one year of observations of the planet and its environment. The EPO Team - an extensive network of individuals and institutions - has sought to convey the excitement and complexity of the mission as MESSENGER's team overcomes challenges, achieves triumphs, and shares the adventure of space exploration with the American and global public. The EPO Team has developed a broad and comprehensive set of educational and outreach activities, ranging from curricular materials, teacher training, and unique mission-related student investigations to museum displays and special outreach to underserved communities and minority students. One of the most visible aspects of this effort is the MESSENGER Educator Fellows program: master science educators who conduct teacher training workshops throughout the nation for pre-K-12 educators. Educator Fellows train teachers on the EPO Team's MESSENGER Education Modules, which are also relevant to other NASA missions reaching important milestones this year (see http://www.messenger-education.org/teachers/educ_modules.php). By the time MESSENGER goes into orbit, Educator Fellows will have trained an estimated 18,000 teachers, who in turn, facilitate classroom experiences to over 1.8 million students. The EPO Team comprises individuals from the American Association for the Advancement of Science (AAAS); Carnegie Academy for Science Education (CASE); Center for Educational Resources (CERES) at Montana State University (MSU) - Bozeman; National Center for Earth and Space Science Education (NCESSE); Johns Hopkins University Applied Physics Laboratory (JHU/APL); National Air and Space Museum (NASM); Science Systems and Applications, Inc. (SSAI); and Southwest Research Institute (SwRI).

The mitochondrial genome of Moniliophthora roreri, the frosty pod rot pathogen of cacao.

PubMed

Costa, Gustavo G L; Cabrera, Odalys G; Tiburcio, Ricardo A; Medrano, Francisco J; Carazzolle, Marcelo F; Thomazella, Daniela P T; Schuster, Stephen C; Carlson, John E; Guiltinan, Mark J; Bailey, Bryan A; Mieczkowski, Piotr; Pereira, Gonçalo A G; Meinhardt, Lyndel W

2012-05-01

In this study, we report the sequence of the mitochondrial (mt) genome of the Basidiomycete fungus Moniliophthora roreri, which is the etiologic agent of frosty pod rot of cacao (Theobroma cacao L.). We also compare it to the mtDNA from the closely-related species Moniliophthora perniciosa, which causes witches' broom disease of cacao. The 94 Kb mtDNA genome of M. roreri has a circular topology and codes for the typical 14 mt genes involved in oxidative phosphorylation. It also codes for both rRNA genes, a ribosomal protein subunit, 13 intronic open reading frames (ORFs), and a full complement of 27 tRNA genes. The conserved genes of M. roreri mtDNA are completely syntenic with homologous genes of the 109 Kb mtDNA of M. perniciosa. As in M. perniciosa, M. roreri mtDNA contains a high number of hypothetical ORFs (28), a remarkable feature that make Moniliophthoras the largest reservoir of hypothetical ORFs among sequenced fungal mtDNA. Additionally, the mt genome of M. roreri has three free invertron-like linear mt plasmids, one of which is very similar to that previously described as integrated into the main M. perniciosa mtDNA molecule. Moniliophthora roreri mtDNA also has a region of suspected plasmid origin containing 15 hypothetical ORFs distributed in both strands. One of these ORFs is similar to an ORF in the mtDNA gene encoding DNA polymerase in Pleurotus ostreatus. The comparison to M. perniciosa showed that the 15 Kb difference in mtDNA sizes is mainly attributed to a lower abundance of repetitive regions in M. roreri (5.8 Kb vs 20.7 Kb). The most notable differences between M. roreri and M. perniciosa mtDNA are attributed to repeats and regions of plasmid origin. These elements might have contributed to the rapid evolution of mtDNA. Since M. roreri is the second species of the genus Moniliophthora whose mtDNA genome has been sequenced, the data presented here contribute valuable information for understanding the evolution of fungal mt genomes among closely-related species. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Expression of metallothionein protein in the lungs of Wistar rats and C57 and DBA mice exposed to cadmium oxide fumes.

PubMed

McKenna, I M; Gordon, T; Chen, L C; Anver, M R; Waalkes, M P

1998-12-01

Chronic exposure to inhaled cadmium (Cd) has been shown to induce lung tumors in rats (Wistar strain) but not in mice (NMRI strain). The protein metallothionein (MT) plays an important role in Cd detoxification, and it has been suggested that differential inducibility of pulmonary MT may lead to interspecies susceptibility differences to inhaled Cd. Interstrain differences in the pulmonary response of the MT gene to Cd stimuli have not been examined in rats or mice. We compared pulmonary MT expression in Wistar Furth (WF) rats with that in DBA and C57 mice, following a single 3-h exposure to CdO fumes containing 1 mg Cd/m3. Induction of the MT gene was assessed by the levels of MT-I and MT-II transcripts, MT-protein content, and number of MT-labeled alveolar and bronchiolar epithelial cells immediately after Cd exposure and 1, 3, and 5 days later. Control animals were exposed to air/argon furnace gases. We observed differential intra- and interspecies inducibility of the MT gene in the lung following Cd inhalation. DBA mice exhibited greater levels of MT-mRNA, mainly for the MT-I isoform, MT-protein content, and number of MT positive cells relative to C57 mice. WF rats showed lower transcription and translation responses of the MT gene upon Cd stimuli than C57 mice. The present results, in concert with our previous findings of higher lung cell proliferation in Cd-exposed C57 relative to DBA mice, predict greater susceptibility of C57 to the carcinogenic effects of inhaled Cd. Furthermore, the low transcriptional and translation responses of the MT gene to Cd stimuli in WF rats might explain the higher susceptibility of this rat strain to develop malignant lung tumors after chronic exposure to Cd via inhalation. Parallel to our findings in mice, differences in the responsiveness of lung MT gene may exist across rat strains. Thus intraspecies genetic variability in pulmonary MT may influence the susceptibility of rats or mice to lung carcinogenesis induced by inhalation of Cd compounds. Copyright 1998 Academic Press.

Transcription profiling suggests that mitochondrial topoisomerase IB acts as a topological barrier and regulator of mitochondrial DNA transcription.

PubMed

Dalla Rosa, Ilaria; Zhang, Hongliang; Khiati, Salim; Wu, Xiaolin; Pommier, Yves

2017-12-08

Mitochondrial DNA (mtDNA) is essential for cell viability because it encodes subunits of the respiratory chain complexes. Mitochondrial topoisomerase IB (TOP1MT) facilitates mtDNA replication by removing DNA topological tensions produced during mtDNA transcription, but it appears to be dispensable. To test whether cells lacking TOP1MT have aberrant mtDNA transcription, we performed mitochondrial transcriptome profiling. To that end, we designed and implemented a customized tiling array, which enabled genome-wide, strand-specific, and simultaneous detection of all mitochondrial transcripts. Our technique revealed that Top1mt KO mouse cells process the mitochondrial transcripts normally but that protein-coding mitochondrial transcripts are elevated. Moreover, we found discrete long noncoding RNAs produced by H-strand transcription and encompassing the noncoding regulatory region of mtDNA in human and murine cells and tissues. Of note, these noncoding RNAs were strongly up-regulated in the absence of TOP1MT. In contrast, 7S DNA, produced by mtDNA replication, was reduced in the Top1mt KO cells. We propose that the long noncoding RNA species in the D-loop region are generated by the extension of H-strand transcripts beyond their canonical stop site and that TOP1MT acts as a topological barrier and regulator for mtDNA transcription and D-loop formation.

Mirror-Touch Synaesthesia Is Not Associated with Heightened Empathy, and Can Occur with Autism

PubMed Central

Baron-Cohen, Simon; Robson, Emma; Lai, Meng-Chuan; Allison, Carrie

2016-01-01

Research has linked Mirror-Touch (MT) synaesthesia with enhanced empathy. We test the largest sample of MT synaesthetes to date to examine two claims that have been previously made: that MT synaesthetes (1) have superior empathy; and (2) only ever experience their MT synaesthesia in response to viewing a person being touched. Given that autism has been suggested to involve deficits in cognitive empathy, we also test two predictions: that MT synaesthetes should (3) be less likely than general population individuals without MT synaesthesia to have an autism spectrum condition (ASC), if MT is characterized by superior empathy; and (4) have fewer autistic traits. We selected three groups: a pure MT synaesthesia group (N = 46), a pure grapheme-colour (GC) synaesthesia group (N = 36), and a typical control group without synaesthesia (N = 46). Participants took three measures of empathy and one measure of autistic traits. MT synaesthetes did not show enhanced empathy. In addition, 30% of all MT synaesthetes recruited into this study (N = 135) reported also having ASC, and MT synaesthetes showed higher autistic trait scores than controls. Finally, some MT experiences were reported in response to viewing objects being touched. Our findings dispute the views that MT synaesthesia is linked with enhanced empathy, is less likely to occur with ASC or elevated autistic traits, and is specific to seeing a person being touched. PMID:27490947

Mirror-Touch Synaesthesia Is Not Associated with Heightened Empathy, and Can Occur with Autism.

PubMed

Baron-Cohen, Simon; Robson, Emma; Lai, Meng-Chuan; Allison, Carrie

2016-01-01

Research has linked Mirror-Touch (MT) synaesthesia with enhanced empathy. We test the largest sample of MT synaesthetes to date to examine two claims that have been previously made: that MT synaesthetes (1) have superior empathy; and (2) only ever experience their MT synaesthesia in response to viewing a person being touched. Given that autism has been suggested to involve deficits in cognitive empathy, we also test two predictions: that MT synaesthetes should (3) be less likely than general population individuals without MT synaesthesia to have an autism spectrum condition (ASC), if MT is characterized by superior empathy; and (4) have fewer autistic traits. We selected three groups: a pure MT synaesthesia group (N = 46), a pure grapheme-colour (GC) synaesthesia group (N = 36), and a typical control group without synaesthesia (N = 46). Participants took three measures of empathy and one measure of autistic traits. MT synaesthetes did not show enhanced empathy. In addition, 30% of all MT synaesthetes recruited into this study (N = 135) reported also having ASC, and MT synaesthetes showed higher autistic trait scores than controls. Finally, some MT experiences were reported in response to viewing objects being touched. Our findings dispute the views that MT synaesthesia is linked with enhanced empathy, is less likely to occur with ASC or elevated autistic traits, and is specific to seeing a person being touched.

Retroviral gene transfer of an antisense construct against membrane type 1 matrix metalloproteinase reduces the invasiveness of rheumatoid arthritis synovial fibroblasts.

PubMed

Rutkauskaite, Edita; Volkmer, Dagmar; Shigeyama, Yukio; Schedel, Jörg; Pap, Geza; Müller-Ladner, Ulf; Meinecke, Ingmar; Alexander, Dorothea; Gay, Renate E; Drynda, Susanne; Neumann, Wolfram; Michel, Beat A; Aicher, Wilhelm K; Gay, Steffen; Pap, Thomas

2005-07-01

Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed prominently in rheumatoid arthritis synovial fibroblasts (RASFs), but the specific contribution of MT1-MMP to fibroblast-mediated destruction of articular cartilage is incompletely understood. This study used gene transfer of an antisense expression construct to assess the effects of MT1-MMP inhibition on the invasiveness of RASFs. Retroviral gene transfer of a pLXIN vector-based antisense RNA expression construct (MT1-MMPalphaS) to MT1-MMP was used to stably transduce RASFs. Levels of MT1-MMP RNA and protein were determined by quantitative polymerase chain reaction, Western blotting, and immunocytochemistry in MT1-MMPalphaS-transduced RASFs as well as in control cells, with monitoring for 60 days. The effects of MT1-MMPalphaS on the invasiveness of RASFs were analyzed in the SCID mouse co-implantation model of RA. MT1-MMPalphaS-transduced RASFs produced high levels of antisense RNA that exceeded endogenous levels of MT1-MMP messenger RNA by 15-fold and resulted in a down-regulation of MT1-MMP at the protein level. Inhibition of MT1-MMP production was maintained for 60 days and significantly reduced the invasiveness of RASFs in the SCID mouse model. Whereas prominent invasion into cartilage by non-transduced and mock-transduced RASFs was observed (mean invasion scores 3.0 and 3.1, respectively), MT1-MMPalphaS-transduced cells showed only moderate invasiveness (mean invasion score 1.8; P < 0.05). The data demonstrate that an antisense RNA expression construct against MT1-MMP can be generated and expressed in RASFs for at least 60 days. Inhibition of MT1-MMP significantly reduces the cartilage degradation by RASFs.

Barley Metallothioneins: MT3 and MT4 Are Localized in the Grain Aleurone Layer and Show Differential Zinc Binding1[W][OA

PubMed Central

Hegelund, Josefine Nymark; Schiller, Michaela; Kichey, Thomas; Hansen, Thomas Hesselhøj; Pedas, Pai; Husted, Søren; Schjoerring, Jan Kofod

2012-01-01

Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins believed to play a role in cytosolic zinc (Zn) and copper (Cu) homeostasis. However, evidence for the functional properties of MTs has been hampered by methodological problems in the isolation and characterization of the proteins. Here, we document that barley (Hordeum vulgare) MT3 and MT4 proteins exist in planta and that they differ in tissue localization as well as in metal coordination chemistry. Combined transcriptional and histological analyses showed temporal and spatial correlations between transcript levels and protein abundance during grain development. MT3 was present in tissues of both maternal and filial origin throughout grain filling. In contrast, MT4 was confined to the embryo and aleurone layer, where it appeared during tissue specialization and remained until maturity. Using state-of-the-art speciation analysis by size-exclusion chromatography inductively coupled plasma mass spectrometry and electrospray ionization time-of-flight mass spectrometry on recombinant MT3 and MT4, their specificity and capacity for metal ion binding were quantified, showing a strong preferential Zn binding relative to Cu and cadmium (Cd) in MT4, which was not the case for MT3. When complementary DNAs from barley MTs were expressed in Cu- or Cd-sensitive yeast mutants, MT3 provided a much stronger complementation than did MT4. We conclude that MT3 may play a housekeeping role in metal homeostasis, while MT4 may function in Zn storage in developing and mature grains. The localization of MT4 and its discrimination against Cd make it an ideal candidate for future biofortification strategies directed toward increasing food and feed Zn concentrations. PMID:22582132

Barley metallothioneins: MT3 and MT4 are localized in the grain aleurone layer and show differential zinc binding.

PubMed

Hegelund, Josefine Nymark; Schiller, Michaela; Kichey, Thomas; Hansen, Thomas Hesselhøj; Pedas, Pai; Husted, Søren; Schjoerring, Jan Kofod

2012-07-01

Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins believed to play a role in cytosolic zinc (Zn) and copper (Cu) homeostasis. However, evidence for the functional properties of MTs has been hampered by methodological problems in the isolation and characterization of the proteins. Here, we document that barley (Hordeum vulgare) MT3 and MT4 proteins exist in planta and that they differ in tissue localization as well as in metal coordination chemistry. Combined transcriptional and histological analyses showed temporal and spatial correlations between transcript levels and protein abundance during grain development. MT3 was present in tissues of both maternal and filial origin throughout grain filling. In contrast, MT4 was confined to the embryo and aleurone layer, where it appeared during tissue specialization and remained until maturity. Using state-of-the-art speciation analysis by size-exclusion chromatography inductively coupled plasma mass spectrometry and electrospray ionization time-of-flight mass spectrometry on recombinant MT3 and MT4, their specificity and capacity for metal ion binding were quantified, showing a strong preferential Zn binding relative to Cu and cadmium (Cd) in MT4, which was not the case for MT3. When complementary DNAs from barley MTs were expressed in Cu- or Cd-sensitive yeast mutants, MT3 provided a much stronger complementation than did MT4. We conclude that MT3 may play a housekeeping role in metal homeostasis, while MT4 may function in Zn storage in developing and mature grains. The localization of MT4 and its discrimination against Cd make it an ideal candidate for future biofortification strategies directed toward increasing food and feed Zn concentrations.

Association of metallothionein-III with oligodendroglial cytoplasmic inclusions in multiple system atrophy.

PubMed

Pountney, D L; Dickson, T C; Power, J H T; Vickers, J C; West, A J; Gai, W P

2011-01-01

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease characterised by Parkinsonian and autonomic symptoms and by widespread intracytoplasmic inclusion bodies in oligodendrocytes. These glial cytoplasmic inclusions (GCIs) are comprised of 9-10 nm filaments rich in the protein alpha-synuclein, also found in neuronal inclusion bodies associated with Parkinson's disease. Metallothioneins (MTs) are a class of low-molecular weight (6-7 kDa), cysteine-rich metal-binding proteins the expression of which is induced by heavy metals, glucocorticoids, cytokines and oxidative stress. Recent studies have shown a role for the ubiquitously expressed MT-I/II isoforms in the brain following a variety of stresses, whereas, the function of the brain-specific MT isoform, MT-III, is less clear. MT-III and MT-I/II immunostaining of post-mortem tissue in MSA and normal control human brains showed that the number of MT-III-positive cells is significantly increased in MSA in visual cortex, whereas MT-I/II isoforms showed no significant difference in the distribution of immunopositive cells in MSA compared to normal tissue. GCIs were immunopositive for MT-III, but were immunonegative for the MT-I/II isoforms. Immunofluorescence double labelling showed the co-localisation of alpha-synuclein and MT-III in GCIs in MSA tissue. In isolated GCIs, transmission electron microscopy demonstrated MT-III immunogold labelling of the amorphous material surrounding alpha-synuclein filaments in GCIs. High-molecular weight MT-III species in addition to MT-III monomer were detected in GCIs by Western analysis of the detergent-solubilised proteins of purified GCIs. These results show that MT-III, but not MT-I/II, is a specific component of GCIs, present in abnormal aggregated forms external to the alpha-synuclein filaments.

Cattle phenotypes can disguise their maternal ancestry.

PubMed

Srirattana, Kanokwan; McCosker, Kieren; Schatz, Tim; St John, Justin C

2017-06-26

Cattle are bred for, amongst other factors, specific traits, including parasite resistance and adaptation to climate. However, the influence and inheritance of mitochondrial DNA (mtDNA) are not usually considered in breeding programmes. In this study, we analysed the mtDNA profiles of cattle from Victoria (VIC), southern Australia, which is a temperate climate, and the Northern Territory (NT), the northern part of Australia, which has a tropical climate, to determine if the mtDNA profiles of these cattle are indicative of breed and phenotype, and whether these profiles are appropriate for their environments. A phylogenetic tree of the full mtDNA sequences of different breeds of cattle, which were obtained from the NCBI database, showed that the mtDNA profiles of cattle do not always reflect their phenotype as some cattle with Bos taurus phenotypes had Bos indicus mtDNA, whilst some cattle with Bos indicus phenotypes had Bos taurus mtDNA. Using D-loop sequencing, we were able to contrast the phenotypes and mtDNA profiles from different species of cattle from the 2 distinct cattle breeding regions of Australia. We found that 67 of the 121 cattle with Bos indicus phenotypes from NT (55.4%) had Bos taurus mtDNA. In VIC, 92 of the 225 cattle with Bos taurus phenotypes (40.9%) possessed Bos indicus mtDNA. When focusing on oocytes from cattle with the Bos taurus phenotype in VIC, their respective oocytes with Bos indicus mtDNA had significantly lower levels of mtDNA copy number compared with oocytes possessing Bos taurus mtDNA (P < 0.01). However, embryos derived from oocytes with Bos indicus mtDNA had the same ability to develop to the blastocyst stage and the levels of mtDNA copy number in their blastocysts were similar to blastocysts derived from oocytes harbouring Bos taurus mtDNA. Nevertheless, oocytes originating from the Bos indicus phenotype exhibited lower developmental potential due to low mtDNA copy number when compared with oocytes from cattle with a Bos taurus phenotype. The phenotype of cattle is not always related to their mtDNA profiles. MtDNA profiles should be considered for breeding programmes as they also influence phenotypic traits and reproductive capacity in terms of oocyte quality.

Mouse models of mitochondrial DNA defects and their relevance for human disease

PubMed Central

Tyynismaa, Henna; Suomalainen, Anu

2009-01-01

Qualitative and quantitative changes in mitochondrial DNA (mtDNA) have been shown to be common causes of inherited neurodegenerative and muscular diseases, and have also been implicated in ageing. These diseases can be caused by primary mtDNA mutations, or by defects in nuclear-encoded mtDNA maintenance proteins that cause secondary mtDNA mutagenesis or instability. Furthermore, it has been proposed that mtDNA copy number affects cellular tolerance to environmental stress. However, the mechanisms that regulate mtDNA copy number and the tissue-specific consequences of mtDNA mutations are largely unknown. As post-mitotic tissues differ greatly from proliferating cultured cells in their need for mtDNA maintenance, and as most mitochondrial diseases affect post-mitotic cell types, the mouse is an important model in which to study mtDNA defects. Here, we review recently developed mouse models, and their contribution to our knowledge of mtDNA maintenance and its role in disease. PMID:19148224

Mitochondrial RNA polymerase is an essential enzyme in erythrocytic stages of Plasmodium falciparum.

PubMed

Ke, Hangjun; Morrisey, Joanne M; Ganesan, Suresh M; Mather, Michael W; Vaidya, Akhil B

2012-09-01

We have shown that transgenic Plasmodium falciparum parasites expressing the yeast DHODH (dihydroorotate dehydrogenase) are independent of the mtETC (mitochondrial electron transport chain), suggesting that they might not need the mitochondrial genome (mtDNA), since it only encodes three protein subunits belonging to the mtETC and fragmentary ribosomal RNA molecules. Disrupting the mitochondrial RNA polymerase (mtRNAP), which is critical for mtDNA replication and transcription, might then cause the generation of a ρ(0) parasite line lacking mtDNA. We made multiple attempts to disrupt the mtRNAP gene by double crossover recombination methods in parasite lines expressing yDHODH either episomally or integrated in the genome, but were unable to produce the desired knockout. We verified that the mtRNAP gene was accessible to recombination by successfully integrating a triple HA tag at the 3' end via single cross-over recombination. These studies suggest that mtRNAP is essential even in mtETC-independent P. falciparum parasites. Copyright © 2012 Elsevier B.V. All rights reserved.

Astronomy in New Zealand

NASA Astrophysics Data System (ADS)

Hearnshaw, John B.

2006-01-01

Although New Zealand is a young country, astronomy played a significant role in its early exploration and discovery during the three voyages of Cook from 1769. In the later 19th century several expeditions came to New Zealand to observe the transits of Venus of 1874 and 1882 and New Zealand's rich history of prominent amateur astronomers dates from this time. The Royal Astronomical Society of New Zealand (founded in 1920) has catered for the amateur community. Professional astronomy however had a slow start in New Zealand. The Carter Observatory was founded in 1941. But it was not until astronomy was taken up by New Zealand's universities, notably by the University of Canterbury from 1963, that a firm basis for research in astronomy and astrophysics was established. Mt John University Observatory with its four optical telescopes (largest 1.8 m) is operated by the University of Canterbury and is the main base for observational astronomy in the country. However four other New Zealand universities also have an interest in astronomical research at the present time. There is also considerable involvement in large international projects such as MOA, SALT, AMOR, IceCube and possibly SKA.

In vivo conformation of mitochondrial DNA revealed by pulsed-field gel electrophoresis in the true slime mold, Physarum polycephalum.

PubMed

Sakurai, R; Sasaki, N; Takano, H; Abe, T; Kawano, S

2000-04-28

Pulsed-field gel electrophoresis (PFGE) was used to examine the in vivo and in vitro conformations of Physarum polycephalum mitochondrial DNA (mtDNA). We used plugs containing isolated mitochondria, isolated mitochondrial nucleoids (mt-nuclei), and isolated mtDNA, in addition to whole cells. The mtDNA contained in the myxamoebae, plasmodia, isolated mitochondria, and isolated mt-nuclei was circular, but most of the isolated mtDNA had been site-specifically fragmented and linearized during DNA preparation and storage under low ionic strength conditions. Restriction mapping of Physarum mtDNA by the direct digestion of the isolated mt-nuclei from two different strains, DP89 x AI16 and KM88 x AI16, resulted in the circular form. A linear mitochondrial plasmid, mF, is known to promote mitochondrial fusion and integration of itself into the mtDNA in Physarum. Linearization of mtDNA by the integration of the mF plasmid was demonstrated when we used PFGE to analyze isolated mitochondria from the plasmodial strain DP89 x NG7 carrying the mF plasmid (mF+). The PFGE system can be used not only to determine whether the form of mtDNA is linear or circular but also to analyze the dynamic conformational changes of mtDNA.

Mindfulness training attenuates the increase in salivary cortisol concentration associated with competition in highly trained wheelchair-basketball players.

PubMed

MacDonald, Luke A; Minahan, Clare L

2018-02-01

This study determined the effect of 8 wk of mindfulness training (MT) on salivary cortisol (sCort) and rate of salivary Immunoglobulin-A (sIgA) secretion in wheelchair-basketball players during a competition period. The mindful group completed 8 weeks of MT in addition to training and competition. sCort and rate of sIgA secretion were measured at baseline, at 2-week intervals, the end and 2 weeks following the intervention. A significant time and group interaction was observed for sCort (F = 3.297, P = 0.040, ES = 0.191); sCort increased in the control group from MT-BL to MT-2wk (P = 0.001) and remained significantly elevated at MT-4wk (P = 0.013) and MT-6wk (P = 0.002). sCort decreased from MT-6wk to MT-8wk (P < 0.001) and concentrations were not different at MT-8wk and Post-2wk to MT-BL (P > 0.05). Mindful group sCort increased from MT-BL to MT-2wk (P = 0.042) but decreased to concentrations no different to MT-BL for the rest of the intervention period (P > 0.05). There were no group differences in rate of sIgA secretion during the intervention (P = 0.810). It was concluded that 8 weeks of MT attenuated the increase in sCort associated with the competition period.

Differential Regulation of Cell Proliferation and Apoptosis by Melatonin Receptor Subtype-Signaling in the Adult Murine Brain.

PubMed

Fredrich, Michaela; Christ, Elmar; Korf, Horst-Werner

2018-06-27

Background/Aims: Zeitgeber time (ZT)-dependent changes in cell proliferation and apoptosis are regulated by melatonin receptor (MT)-mediated signaling in the adult hippocampus and hypothalamic-hypophyseal system. There are two G-protein-coupled MT-subtypes, MT1 and MT2. Therefore, the present study examined which MT-subtype is required for regulation of ZT-dependent changes in cell proliferation and/or apoptosis in the adult murine brain and pituitary. Adult melatonin-proficient (C3H) mice with targeted deletion of MT1 (MT1 KO) or MT2 (MT2 KO) were adapted to a 12-hour light, 12-hour dark photoperiod and sacrificed at ZT00, ZT06, ZT12, and ZT18. Immunohistochemistry for Ki67 or activated caspase-3 served to quantify proliferating and apoptotic cells in the hippocampal subgranular zone (SGZ) and granule cell layer, the hypothalamic median eminence (ME), and the hypophyseal pars tuberalis. ZT-dependent changes in cell proliferation were found exclusively in the SGZ and ME of MT1 KO mice, while apoptosis showed no ZT-dependent changes in the regions analyzed, neither in MT1 nor in MT2 KO mice. Comparison with our previous studies in C3H mice with functional MTs and MT1/2 KO mice revealed that MT2-mediated signaling is required and sufficient for ZT-dependent changes in cell proliferation in the SGZ and ME, while ZT-dependent changes in apoptosis require signaling from both MT-subtypes. Our results indicate that generation and timing of ZT-dependent changes in cell proliferation and apoptosis by melatonin require different MT-subtype-constellations and emphasize the importance to shed light on the specific function of each receptor-subtype in different tissues and physiological conditions.
. ©2018S. Karger AG, Basel.

A new Starlight Reserve for the central South Island of New Zealand

NASA Astrophysics Data System (ADS)

Hearnshaw, John

2015-03-01

The Aoraki Mackenzie International Dark Sky Reserve is a new reserve created in 2012 by the International Dark-Sky Association in the central South Island of New Zealand, and covers over 4300 square kilometres around Mt John University Observatory. It is the first such reserve to be recognized at gold tier level and is the largest dark sky reserve in the world. Astro-tourism in the new reserve will be a prominent activity in the coming years.

Quasi-local energy in presence of gravitational radiation

NASA Astrophysics Data System (ADS)

Chen, Po-Ning; Wang, Mu-Tao; Yau, Shing-Tung

2016-07-01

We discuss our recent work [P.-N. Chen, M.-T. Wang and S.-T. Yau, Quasi-local mass in the gravitational perturbations of black holes, to appear.] in which gravitational radiation was studied by evaluating the Wang-Yau quasi-local mass of surfaces of fixed size at the infinity of both axial and polar perturbations of the Schwarzschild spacetime, à la Chandrasekhar. [S. Chandrasekhar, The Mathematical Theory of Black Holes, Oxford Classic Texts in the Physical Sciences (Oxford University Press, New York, 1998).

Low-cost enclosure for the sub-millimeter telescope

NASA Astrophysics Data System (ADS)

Ulich, B. L.; Hoffmann, W. F.; Davison, W. B.; Baars, J. W. M.; Mezger, P. G.

1984-01-01

The University of Arizona and the Max-Planck-Institut fuer Radioastronomie are collaborating to construct a submillimeter-wavelength radio telescope facility at the summit of Mt. Lemmon (2791 m above sea level) near Tucson, Arizona. A corotating building has been designed to protect the 10 m-diameter Submillimeter Telescope against storm damage, to provide large instrumentation rooms at the Nasmyth foci, and to minimize degradation of the reflector profile accuracy and pointing errors caused by wind forces and solar radiation.

Low-Cost Enclosure For The Sub-Millimeter Telescope

NASA Astrophysics Data System (ADS)

Ulich, Bobby L.; Hoffmann, William F.; Davison, Warren B.; Baars, Jacob W. M.; Mezger, Peter G.

1983-11-01

The University of Arizona and the Max-Planck-Institut fur Radioastronomie are collaborating to construct a sub-millimeter wavelength radio telescope facility at the summit of Mt. Lemmon (2791 m above sea level) near Tucson, Arizona. We have designed a corotating building to protect the 10 m diameter Sub-Millimeter Telescope (SMT) against storm damage, to provide large instrumentation rooms at the Nasmyth foci, and to minimize degradation of the reflector profile accuracy and pointing errors caused by wind forces and solar radiation.

Sensitivity of Tropical Cyclone Models to the Surface Drag Coefficient in Different Boundary-Layer Schemes

DTIC Science & Technology

2011-10-20

altitude of about 500 m in Hurricanes Allen (1980) and Hugo (1989) by Zhang et al. (2010). In Hugo these were about 110 m2 s−1 beneath the eyewall...Marks FD Montgomery MT Lorsolo S. 2010 Estimation of turbulence characteristics of eyewall boundary layer of Hurricane Hugo (1989) Mon. Wea. Rev., in...University of Munich, Munich, Germany b Dept. of Meteorology, Naval Postgraduate School, Monterey, CA & NOAA’s Hurricane Research Division ∗Correspondence

Colors of Outer Solar System Objects Measured with VATT

NASA Astrophysics Data System (ADS)

Romanishin, William; Tegler, S. C.; Consolmagno, G. J.

2010-10-01

Over the past 7 years, we have measured optical B-V and V-R colors for about 40 minor outer solar system objects using the 1.8-m Vatican Advanced Technology Telescope (VATT) located on Mt. Graham in southeast Arizona. We will present these colors and use them to update the discussion of colors of minor bodies in the outer solar system. We gratefully acknowledge funding from the NASA Planetary Astronomy Program to Northern Arizona University and the U. of Oklahoma which helped support this work.

Observations on Bubble Dynamics at High Pressures and Bubble Dynamics in Stagnation Flow.

DTIC Science & Technology

1982-11-30

reverse side It nocooeuAn aifdentifly by block mt..bet) S 1 Cavitation, High Speed Photography, Ruby Laser . 20. AFSTAACT Co.nflno on revere side Of...AT NIGH ASIE3r.T PRESSUrES A.T. Ellis and J.E. Starrect University of California, San Diego Recent developsent by the authors of a unique ruby laser ...1,000,300 frames per second with exposure clue of approximately 2vl0- seconds. The coherent nature of the laser illuminacion revealed shock waves

NASA missions studies magnetic space explosions

NASA Image and Video Library

2017-12-08

Every day, invisible magnetic explosions are happening around Earth, on the surface of the sun and across the universe. These explosions, known as magnetic reconnection, occur when magnetic field lines cross, releasing stored magnetic energy. Such explosions are a key way that clouds of charged particles — plasmas — are accelerated throughout the universe. In Earth’s magnetosphere — the giant magnetic bubble surrounding our planet — these magnetic reconnections can fling charged particles toward Earth, triggering auroras. Read more: go.nasa.gov/2mnMtDm Video caption - In this simulation, a reconnection even pushes a blob of plasma toward Earth. The jet blown in the opposite direction wobbles due to the unstable conditions. Credit: NASA’s Goddard Space Flight Center/Yi-Hsin Liu/Joy Ng, producer

Preface

NASA Astrophysics Data System (ADS)

Makabe, Toshiaki; Samukawa, Seiji

2007-06-01

Twenty-first century will be the era of the design technology on a firm basis of physics and chemistry under circumstances of a prospective high-speed computing along the line of environmentally friendly and economically saving society. The 4th International Workshop on Basic Aspects of Nonequilibrium Plasmas Interacting with Surfaces (BANPIS); Negative ions, their function & designability, and the 4th EU-Japan Joint Symposium on Plasma Processes (JSPP) were held at Hotel Highland Resort close to Mt. Fuji in Japan on January 30 - February 1, 2006. The joint conference was organized by the 21st century Center of Excellence (COE) for ;Optical & Electronic Device Technology for Access Networks; in Keio University, and co-operated by the Center for ;Atomic and Molecular Engineering,; in Open University, and by The Japan Society of Applied Physics.

44 CFR 15.3 - Access to Mt. Weather.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and areas...

44 CFR 15.3 - Access to Mt. Weather.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and areas...

44 CFR 15.3 - Access to Mt. Weather.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and areas...

44 CFR 15.3 - Access to Mt. Weather.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and areas...

44 CFR 15.3 - Access to Mt. Weather.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Access to Mt. Weather. 15.3... HOMELAND SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING CENTER § 15.3 Access to Mt. Weather. Mt. Weather contains classified material and areas...

Heteromeric MT1/MT2 Melatonin Receptors Modulate Photoreceptor Function

PubMed Central

Baba, Kenkichi; Benleulmi-Chaachoua, Abla; Journé, Anne-Sophie; Kamal, Maud; Guillaume, Jean-Luc; Dussaud, Sébastien; Gbahou, Florence; Yettou, Katia; Liu, Cuimei; Contreras-Alcantara, Susana; Jockers, Ralf; Tosini, Gianluca

2013-01-01

The formation of G protein-coupled receptor (GPCR) heteromers elicits signaling diversification and holds great promise for improved drug selectivity. Most studies have been conducted in heterologous expression systems; however, in vivo validation is missing from most cases thus questioning the physiological significance of GPCR heteromerization. Melatonin MT1 and MT2 receptors have been shown to exist as homo- and heteromers in vitro. We show here that the effect of melatonin on rod photoreceptor light sensitivity is mediated by melatonin MT1/MT2 receptor heteromers. This effect involves activation of the heteromer-specific PLC/PKC pathway and is abolished in MT1−/− and MT2−/− mice as well as in mice overexpressing a non-functional MT2 receptor mutant that competes with the formation of functional MT1/MT2 heteromers in photoreceptor cells. This study establishes the essential role of melatonin receptor heteromers in retinal function and supports the physiological importance of GPCR heteromerization. Finally, our work may have important therapeutic implications, as the heteromer complex may provide a unique pharmacological target to improve photoreceptor functioning and to extend the viability of photoreceptors during aging. PMID:24106342

A tethering mechanism controls the processivity and kinetochore-microtubule plus-end enrichment of the kinesin-8 Kif18A

PubMed Central

Stumpff, Jason; Du, Yaqing; English, Chauca A.; Maliga, Zoltan; Wagenbach, Michael; Asbury, Charles L.; Wordeman, Linda; Ohi, Ryoma

2011-01-01

Summary Metaphase chromosome positioning depends on Kif18A, a kinesin-8 that accumulates at and suppresses the dynamics of K-MT plus ends. By engineering Kif18A mutants that suppress MT dynamics but fail to concentrate at K-MT plus-ends, we identify a mechanism that allows Kif18A to accumulate at K-MT plus ends to a level required to suppress chromosome movements. Enrichment of Kif18A at K-MT plus-ends depends on its C-terminal tail domain, while the ability of Kif18A to suppress MT growth is conferred by the N-terminal motor domain. The Kif18A tail contains a second MT-binding domain that diffuses along the MT lattice, suggesting that it tethers the motor to the MT track. Consistently, the tail enhances Kif18A processivity and is crucial for it to accumulate at K-MT plus-ends. The heightened processivity of Kif18A, conferred by its tail domain, thus promotes concentration of Kif18A at K-MT plus-ends, where it suppresses their dynamics to control chromosome movements. PMID:21884977

Drosophila mitochondrial transcription factor B1 modulates mitochondrial translation but not transcription or DNA copy number in Schneider cells.

PubMed

Matsushima, Yuichi; Adán, Cristina; Garesse, Rafael; Kaguni, Laurie S

2005-04-29

We report the cloning and molecular analysis of Drosophila mitochondrial transcription factor (d-mtTF) B1. An RNA interference (RNAi) construct was designed that reduces expression of d-mtTFB1 to 5% of its normal level in Schneider cells. In striking contrast with our previous study on d-mtTFB2, we found that RNAi knock-down of d-mtTFB1 does not change the abundance of specific mitochondrial RNA transcripts, nor does it affect the copy number of mitochondrial DNA. In a corollary manner, overexpression of d-mtTFB1 did not increase either the abundance of mitochondrial RNA transcripts or mitochondrial DNA copy number. Our data suggest that, unlike d-mtTFB2, d-mtTFB1 does not have a critical role in either transcription or regulation of the copy number of mitochondrial DNA. Instead, because we found that RNAi knockdown of d-mtTFB1 reduces mitochondrial protein synthesis, we propose that it serves its primary role in modulating translation. Our work represents the first study to document the role of mtTFB1 in vivo and establishes clearly functional differences between mtTFB1 and mtTFB2.

Crosstalk between mitochondrial stress signals regulates yeast chronological lifespan.

PubMed

Schroeder, Elizabeth A; Shadel, Gerald S

2014-01-01

Mitochondrial DNA (mtDNA) exists in multiple copies per cell and is essential for oxidative phosphorylation. Depleted or mutated mtDNA promotes numerous human diseases and may contribute to aging. Reduced TORC1 signaling in the budding yeast, Saccharomyces cerevisiae, extends chronological lifespan (CLS) in part by generating a mitochondrial ROS (mtROS) signal that epigenetically alters nuclear gene expression. To address the potential requirement for mtDNA maintenance in this response, we analyzed strains lacking the mitochondrial base-excision repair enzyme Ntg1p. Extension of CLS by mtROS signaling and reduced TORC1 activity, but not caloric restriction, was abrogated in ntg1Δ strains that exhibited mtDNA depletion without defects in respiration. The DNA damage response (DDR) kinase Rad53p, which transduces pro-longevity mtROS signals, is also activated in ntg1Δ strains. Restoring mtDNA copy number alleviated Rad53p activation and re-established CLS extension following mtROS signaling, indicating that Rad53p senses mtDNA depletion directly. Finally, DDR kinases regulate nucleus-mitochondria localization dynamics of Ntg1p. From these results, we conclude that the DDR pathway senses and may regulate Ntg1p-dependent mtDNA stability. Furthermore, Rad53p senses multiple mitochondrial stresses in a hierarchical manner to elicit specific physiological outcomes, exemplified by mtDNA depletion overriding the ability of Rad53p to transduce an adaptive mtROS longevity signal. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Differential Expression of Metallothionein Isoforms in Terrestrial Snail Embryos Reflects Early Life Stage Adaptation to Metal Stress

PubMed Central

Baurand, Pierre-Emmanuel; Pedrini-Martha, Veronika; de Vaufleury, Annette; Niederwanger, Michael; Capelli, Nicolas; Scheifler, Renaud; Dallinger, Reinhard

2015-01-01

The aim of this study was to analyze the expression of three metallothionein (MT) isoform genes (CdMT, CuMT and Cd/CuMT), already known from adults, in the Early Life Stage (ELS) of Cantareus aspersus. This was accomplished by detection of the MT isoform-specific transcription adopting Polymerase Chain Reaction (PCR) amplification and quantitative Real Time (qRT)-PCR of the three MT genes. Freshly laid eggs were kept for 24 hours under control conditions or exposed to three cadmium (Cd) solutions of increasing concentration (5, 10, and 15 mg Cd/L). The transcription of the three MT isoform genes was detected via PCR in 1, 6 and 12-day-old control or Cd-exposed embryos. Moreover, the transcription of this isoform genes during development was followed by qRT-PCR in 6 and 12-day-old embryos. Our results showed that the CdMT and Cd/CuMT genes, but not the CuMT gene, are expressed in embryos at the first day of development. The transcription of the 3 MT genes in control embryos increased with development time, suggesting that the capacities of metal regulation and detoxification may have gradually increased throughout embryogenesis. However in control embryos, the most highly expressed MT gene was that of the Cd/CuMT isoform, whose transcription levels greatly exceeded those of the other two MT genes. This contrasts with the minor significance of this gene in adult snails and suggests that in embryos, this isoform may play a comparatively more important role in metal physiology compared to adult individuals. This function in adult snails appears not to be related to Cd detoxification. Instead, snail embryos responded to Cd exposure by over-expression of the CdMT gene in a concentration-dependent manner, whereas the expression of the Cd/CuMT gene remained unaffected. Moreover, our study demonstrates the ability of snail embryos to respond very early to Cd exposure by up-regulation of the CdMT gene. PMID:25706953

In vivo imaging of membrane type-1 matrix metalloproteinase with a novel activatable near-infrared fluorescence probe.

PubMed

Shimizu, Yoichi; Temma, Takashi; Hara, Isao; Makino, Akira; Kondo, Naoya; Ozeki, Ei-Ichi; Ono, Masahiro; Saji, Hideo

2014-08-01

Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease activating MMP-2 that mediates cleavage of extracellular matrix components and plays pivotal roles in tumor migration, invasion and metastasis. Because in vivo noninvasive imaging of MT1-MMP would be useful for tumor diagnosis, we developed a novel near-infrared (NIR) fluorescence probe that can be activated following interaction with MT1-MMP in vivo. MT1-hIC7L is an activatable fluorescence probe comprised of anti-MT1-MMP monoclonal antibodies conjugated to self-assembling polymer micelles that encapsulate NIR dyes (IC7-1, λem : 858 nm) at concentrations sufficient to cause fluorescence self-quenching. In aqueous buffer, MT1-hIC7L fluorescence was suppressed to background levels and increased approximately 35.5-fold in the presence of detergent. Cellular uptake experiments revealed that in MT1-MMP positive C6 glioma cells, MT1-hIC7L showed significantly higher fluorescence that increased with time as compared to hIC7L, a negative control probe lacking the anti-MT1-MMP monoclonal antibody. In MT1-MMP negative MCF-7 breast adenocarcinoma cells, both MT1-hIC7L and hIC7L showed no obvious fluorescence. In addition, the fluorescence intensity of C6 cells treated with MT1-hIC7L was suppressed by pre-treatment with an MT1-MMP endocytosis inhibitor (P < 0.05). In vivo optical imaging using probes intravenously administered to tumor-bearing mice showed that MT1-hIC7L specifically visualized C6 tumors (tumor-to-background ratios: 3.8 ± 0.3 [MT1-hIC7L] vs 3.1 ± 0.2 [hIC7L] 48 h after administration, P < 0.05), while the probes showed similarly low fluorescence in MCF-7 tumors. Together, these results show that MT1-hIC7L would be a potential activatable NIR probe for specifically detecting MT1-MMP-expressing tumors. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

The mitochondrial genome of the gymnosperm Cycas taitungensis contains a novel family of short interspersed elements, Bpu sequences, and abundant RNA editing sites.

PubMed

Chaw, Shu-Miaw; Shih, Arthur Chun-Chieh; Wang, Daryi; Wu, Yu-Wei; Liu, Shu-Mei; Chou, The-Yuan

2008-03-01

The mtDNA of Cycas taitungensis is a circular molecule of 414,903 bp, making it 2- to 6-fold larger than the known mtDNAs of charophytes and bryophytes, but similar to the average of 7 elucidated angiosperm mtDNAs. It is characterized by abundant RNA editing sites (1,084), more than twice the number found in the angiosperm mtDNAs. The A + T content of Cycas mtDNA is 53.1%, the lowest among known land plants. About 5% of the Cycas mtDNA is composed of a novel family of mobile elements, which we designated as "Bpu sequences." They share a consensus sequence of 36 bp with 2 terminal direct repeats (AAGG) and a recognition site for the Bpu 10I restriction endonuclease (CCTGAAGC). Comparison of the Cycas mtDNA with other plant mtDNAs revealed many new insights into the biology and evolution of land plant mtDNAs. For example, the noncoding sequences in mtDNAs have drastically expanded as land plants have evolved, with abrupt increases appearing in the bryophytes, and then in the seed plants. As a result, the genomic organizations of seed plant mtDNAs are much less compact than in other plants. Also, the Cycas mtDNA appears to have been exempted from the frequent gene loss observed in angiosperm mtDNAs. Similar to the angiosperms, the 3 Cycas genes nad1, nad2, and nad5 are disrupted by 5 group II intron squences, which have brought the genes into trans-splicing arrangements. The evolutionary origin and invasion/duplication mechanism of the Bpu sequences in Cycas mtDNA are hypothesized and discussed.

Mitochondrial DNA damage is associated with damage accrual and disease duration in patients with Systemic Lupus Erythematosus

PubMed Central

López-López, Linnette; Nieves-Plaza, Mariely; Castro, María del R.; Font, Yvonne M.; Torres-Ramos, Carlos; Vilá, Luis M.; Ayala-Peña, Sylvette

2014-01-01

Objective To determine the extent of mitochondrial DNA (mtDNA) damage in systemic lupus erythematosus (SLE) patients compared to healthy subjects and to determine the factors associated with mtDNA damage among SLE patients. Methods A cross-sectional study was performed in 86 SLE patients (per American College of Rheumatology classification criteria) and 86 healthy individuals matched for age and gender. Peripheral blood mononuclear cells (PBMCs) were collected from subjects to assess the relative amounts of mtDNA damage. Quantitative polymerase chain reaction assay was used to measure the frequency of mtDNA lesions and mtDNA abundance. Socioeconomic-demographic features, clinical manifestations, pharmacologic treatment, disease activity, and damage accrual were determined. Statistical analyses were performed using t test, pairwise correlation, and Pearson’s chi-square test (or Fisher’s exact test) as appropriate. Results Among SLE patients, 93.0% were women. The mean (SD) age was 38.0 (10.4) years and the mean (SD) disease duration was 8.7 (7.5) years. SLE patients exhibited increased levels of mtDNA damage as shown by higher levels of mtDNA lesions and decreased mtDNA abundance as compared to healthy individuals. There was a negative correlation between disease damage and mtDNA abundance and a positive correlation between mtDNA lesions and disease duration. No association was found between disease activity and mtDNA damage. Conclusion PBMCs from SLE patients exhibited more mtDNA damage compared to healthy subjects. Higher levels of mtDNA damage were observed among SLE patients with major organ involvement and damage accrual. These results suggest that mtDNA damage have a potential role in the pathogenesis of SLE. PMID:24899636

Mitochondrial DNA damage is associated with damage accrual and disease duration in patients with systemic lupus erythematosus.

PubMed

López-López, L; Nieves-Plaza, M; Castro, M del R; Font, Y M; Torres-Ramos, C A; Vilá, L M; Ayala-Peña, S

2014-10-01

To determine the extent of mitochondrial DNA (mtDNA) damage in systemic lupus erythematosus (SLE) patients compared to healthy subjects and to determine the factors associated with mtDNA damage among SLE patients. A cross-sectional study was performed in 86 SLE patients (per American College of Rheumatology classification criteria) and 86 healthy individuals matched for age and gender. Peripheral blood mononuclear cells (PBMCs) were collected from subjects to assess the relative amounts of mtDNA damage. Quantitative polymerase chain reaction assay was used to measure the frequency of mtDNA lesions and mtDNA abundance. Socioeconomic-demographic features, clinical manifestations, pharmacologic treatment, disease activity, and damage accrual were determined. Statistical analyses were performed using t test, pairwise correlation, and Pearson's chi-square test (or Fisher's exact test) as appropriate. Among SLE patients, 93.0% were women. The mean (SD) age was 38.0 (10.4) years and the mean (SD) disease duration was 8.7 (7.5) years. SLE patients exhibited increased levels of mtDNA damage as shown by higher levels of mtDNA lesions and decreased mtDNA abundance as compared to healthy individuals. There was a negative correlation between disease damage and mtDNA abundance and a positive correlation between mtDNA lesions and disease duration. No association was found between disease activity and mtDNA damage. PBMCs from SLE patients exhibited more mtDNA damage compared to healthy subjects. Higher levels of mtDNA damage were observed among SLE patients with major organ involvement and damage accrual. These results suggest that mtDNA damage have a potential role in the pathogenesis of SLE. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Uptake and depletion of plasma 17alpha-methyltestosterone during induction of masculinization in muskellunge, Esox masquinongy: effect on plasma steroids and sex reversal.

PubMed

Rinchard, J; Dabrowski, K; Garcia-Abiado, M A; Ottobre, J

1999-08-01

Oral administration of 17alpha-methyltestosterone (MT) was used to induce masculinization of sexually undifferentiated muskellunge, Esox masquinongy. Three groups of muskellunge (mean weight, 2.5 +/- 0.6 g) were submitted to MT treatment (15 mg of MT/kg) for 60 days. An additional one group was used as a control (hormone-free diet). Food was distributed over a 10-h period by using automatic belt feeders. Blood was sampled in both control and treated fish at different intervals during and after feeding: before (0 h), at 3 h, 6 h, and cessation of feeding (10 h), and after a fast of 22 h (32 h). MT had no significant effect on growth and survival in muskellunge 6 months after the treatment. Concentrations of plasma MT increased during the feeding period and reached their maximum levels 6 or 10 h after starting feeding. This rapid increase of MT indicated a rapid absorption of this steroid. Plasma MT levels then declined and reached a radir by 22 h after cessation of feeding, suggesting that MT is rapidly metabolized and excreted. The profiles of plasma testosterone during the MT treatment did not differ significantly between control and MT-treated groups. During and after the MT treatment, the concentration of plasma testosterone did not differ significantly between control and MT-treated groups. Moreover, no sexual dimorphism of testosterone levels was observed. Six months after treatment, the sex ratio in MT-treated groups (33% males, 62% females, and 5% intersex) was opposite to control (70% and 30%, respectively) and differed significantly. This suggests that at 15 mg of MT/kg over 60 days, a paradoxical feminization took place.

Functional mapping of protein-protein interactions in an enzyme complex by directed evolution.

PubMed

Roderer, Kathrin; Neuenschwander, Martin; Codoni, Giosiana; Sasso, Severin; Gamper, Marianne; Kast, Peter

2014-01-01

The shikimate pathway enzyme chorismate mutase converts chorismate into prephenate, a precursor of Tyr and Phe. The intracellular chorismate mutase (MtCM) of Mycobacterium tuberculosis is poorly active on its own, but becomes >100-fold more efficient upon formation of a complex with the first enzyme of the shikimate pathway, 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (MtDS). The crystal structure of the enzyme complex revealed involvement of C-terminal MtCM residues with the MtDS interface. Here we employed evolutionary strategies to probe the tolerance to substitution of the C-terminal MtCM residues from positions 84-90. Variants with randomized positions were subjected to stringent selection in vivo requiring productive interactions with MtDS for survival. Sequence patterns identified in active library members coincide with residue conservation in natural chorismate mutases of the AroQδ subclass to which MtCM belongs. An Arg-Gly dyad at positions 85 and 86, invariant in AroQδ sequences, was intolerant to mutation, whereas Leu88 and Gly89 exhibited a preference for small and hydrophobic residues in functional MtCM-MtDS complexes. In the absence of MtDS, selection under relaxed conditions identifies positions 84-86 as MtCM integrity determinants, suggesting that the more C-terminal residues function in the activation by MtDS. Several MtCM variants, purified using a novel plasmid-based T7 RNA polymerase gene expression system, showed that a diminished ability to physically interact with MtDS correlates with reduced activatability and feedback regulatory control by Tyr and Phe. Mapping critical protein-protein interaction sites by evolutionary strategies may pinpoint promising targets for drugs that interfere with the activity of protein complexes.

Functional Mapping of Protein-Protein Interactions in an Enzyme Complex by Directed Evolution

PubMed Central

Roderer, Kathrin; Neuenschwander, Martin; Codoni, Giosiana; Sasso, Severin; Gamper, Marianne; Kast, Peter

2014-01-01

The shikimate pathway enzyme chorismate mutase converts chorismate into prephenate, a precursor of Tyr and Phe. The intracellular chorismate mutase (MtCM) of Mycobacterium tuberculosis is poorly active on its own, but becomes >100-fold more efficient upon formation of a complex with the first enzyme of the shikimate pathway, 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (MtDS). The crystal structure of the enzyme complex revealed involvement of C-terminal MtCM residues with the MtDS interface. Here we employed evolutionary strategies to probe the tolerance to substitution of the C-terminal MtCM residues from positions 84–90. Variants with randomized positions were subjected to stringent selection in vivo requiring productive interactions with MtDS for survival. Sequence patterns identified in active library members coincide with residue conservation in natural chorismate mutases of the AroQδ subclass to which MtCM belongs. An Arg-Gly dyad at positions 85 and 86, invariant in AroQδ sequences, was intolerant to mutation, whereas Leu88 and Gly89 exhibited a preference for small and hydrophobic residues in functional MtCM-MtDS complexes. In the absence of MtDS, selection under relaxed conditions identifies positions 84–86 as MtCM integrity determinants, suggesting that the more C-terminal residues function in the activation by MtDS. Several MtCM variants, purified using a novel plasmid-based T7 RNA polymerase gene expression system, showed that a diminished ability to physically interact with MtDS correlates with reduced activatability and feedback regulatory control by Tyr and Phe. Mapping critical protein-protein interaction sites by evolutionary strategies may pinpoint promising targets for drugs that interfere with the activity of protein complexes. PMID:25551646

Rhenium and technetium tricarbonyl, {M(CO)3} (+) (M = Tc, Re), binding to mammalian metallothioneins: new insights into chemical and radiopharmaceutical implications.

PubMed

Lecina, Joan; Palacios, Òscar; Atrian, Sílvia; Capdevila, Mercè; Suades, Joan

2015-04-01

This paper deals with the binding of the four mammalian metallothioneins (MTs) to the organometallic metal fragment {fac-M(CO)3}(+) (M = (99)Tc, Re), which is highly promising for the preparation of second-generation radiopharmaceuticals. The study of the transmetallation reaction between zinc and rhenium in Zn7-MT1 by means of UV-vis and CD spectroscopy demonstrated the incorporation of the {fac-Re(CO)3}(+) fragment to the MTs. This reaction should be performed at 70 °C to accelerate the reaction rate, a result that is consistent with the reported reactivity of the rhenium fragment. ESI-TOF MS demonstrated the formation of mixed-metal species as Zn6,{Re(CO)3}-MT, Zn6,{Re(CO)3}2-MT, and Zn5,{Re(CO)3}3-MT, as well as the different reactivity of the four MT isoforms. Hence, Zn-MT3 showed the highest reactivity, in agreement with its high Cu-thionein character, whereas Zn-MT2 exhibited the lowest reactivity, in line with its high Zn-thionein character. The reactivity of the Zn-loaded forms of MT1 and MT4 is intermediate between those of MT3 and MT2. The study of the binding of the {fac-(99)Tc(CO)3}(+) fragment to MTs showed a significant and very interesting different reactivity in relation to rhenium. The transmetallation reaction is much more effective with technetium than with rhenium and significant amounts of mixed Zn x ,{(99)Tc(CO)3} y -MT species were formed with the four MT isoforms whereas only MT3 rendered similar amounts of rhenium derivatives. The results obtained in this study support the possible use of technetium for labelling mammalian metallothioneins and also for possible radiopharmaceutical applications.

The Metallothionein-Null Phenotype Is Associated with Heightened Sensitivity to Lead Toxicity and an Inability to Form Inclusion Bodies

PubMed Central

Qu, Wei; Diwan, Bhalchandra A.; Liu, Jie; Goyer, Robert A.; Dawson, Tammy; Horton, John L.; Cherian, M. George; Waalkes, Michael P.

2002-01-01

Susceptibility to lead toxicity in MT-null mice and cells, lacking the major forms of the metallothionein (MT) gene, was compared to wild-type (WT) mice or cells. Male MT-null and WT mice received lead in the drinking water (0 to 4000 ppm) for 10 to 20 weeks. Lead did not alter body weight in any group. Unlike WT mice, lead-treated MT-null mice showed dose-related nephromegaly. In addition, after lead exposure renal function was significantly diminished in MT-null mice in comparison to WT mice. MT-null mice accumulated less renal lead than WT mice and did not form lead inclusion bodies, which were present in the kidneys of WT mice. In gene array analysis, renal glutathione S-transferases were up-regulated after lead in MT-null mice only. In vitro studies on fibroblast cell lines derived from MT-null and WT mice showed that MT-null cells were much more sensitive to lead cytotoxicity. MT-null cells accumulated less lead and formed no inclusion bodies. The MT-null phenotype seems to preclude lead-induced inclusion body formation and increases lead toxicity at the organ and cellular level despite reducing lead accumulation. This study reveals important roles for MT in chronic lead toxicity, lead accumulation, and inclusion body formation. PMID:11891201

Mitotic Kinesin CENP-E Promotes Microtubule Plus-End Elongation

PubMed Central

Sardar, Harjinder S.; Luczak, Vincent G.; Lopez, Maria M.; Lister, Bradford C.; Gilbert, Susan P.

2010-01-01

Summary Centromere protein CENP-E is a dimeric kinesin (Kinesin-7 family) with critical roles in mitosis including establishment of microtubule (MT)-chromosome linkage and movement of monooriented chromosomes on kinetochore microtubules (kMTs) for proper alignment at metaphase [1-9]. We performed studies to test the hypothesis that CENP-E promotes MT elongation at the MT plus-ends. A human CENP-E construct was engineered, expressed, and purified which yielded the CENP-E-6His dimeric motor protein. The results show that CENP-E promotes MT plus-end directed MT gliding at 11 nm/s. The results from real-time microscopy assays indicate that 60.3% of polarity marked MTs exhibited CENP-E promoted MT plus-end elongation. The MT extension required ATP turnover, and MT plus-end elongation occurred at 1.48 μm/30 min. Immunolocalization studies revealed that 80.8% of plus-end elongated MTs showed CENP-E at the MT plus-end. The time dependence of CENP-E promoted MT elongation in solution best fit a single exponential function (kobs = 5.1 s−1), which is indicative of a mechanism in which α,β-tubulin subunit addition is tightly coupled to ATP turnover. Based on these results, we propose that CENP-E as part of its function in chromosome kinetochore-MT linkage plays a direct role in MT elongation. PMID:20797864

MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis.

PubMed

Rebustini, Ivan T; Myers, Christopher; Lassiter, Keyonica S; Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn; Pedchenko, Vadim; Hudson, Billy G; Hoffman, Matthew P

2009-10-01

Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here, we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Specifically, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA treatment, increasing MT-MMP and proproliferative gene expression via beta1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis.

More evidence for non-maternal inheritance of mitochondrial DNA?

PubMed

Bandelt, H-J; Kong, Q-P; Parson, W; Salas, A

2005-12-01

A single case of paternal co-transmission of mitochondrial DNA (mtDNA) in humans has been reported so far. To find potential instances of non-maternal inheritance of mtDNA. Published medical case studies (of single patients) were searched for irregular mtDNA patterns by comparing the given haplotype information for different clones or tissues with the worldwide mtDNA database as known to date-a method that has proved robust and reliable for the detection of flawed mtDNA sequence data. More than 20 studies were found reporting clear cut instances with mtDNAs of different ancestries in single individuals. As examples, cases are reviewed from recent published reports which, at face value, may be taken as evidence for paternal inheritance of mtDNA or recombination. Multiple types (or recombinant types) of quite dissimilar mitochondrial DNA from different parts of the known mtDNA phylogeny are often reported in single individuals. From re-analyses and corrigenda of forensic mtDNA data, it is apparent that the phenomenon of mixed or mosaic mtDNA can be ascribed solely to contamination and sample mix up.

Stochastic modelling, Bayesian inference, and new in vivo measurements elucidate the debated mtDNA bottleneck mechanism

PubMed Central

Johnston, Iain G; Burgstaller, Joerg P; Havlicek, Vitezslav; Kolbe, Thomas; Rülicke, Thomas; Brem, Gottfried; Poulton, Jo; Jones, Nick S

2015-01-01

Dangerous damage to mitochondrial DNA (mtDNA) can be ameliorated during mammalian development through a highly debated mechanism called the mtDNA bottleneck. Uncertainty surrounding this process limits our ability to address inherited mtDNA diseases. We produce a new, physically motivated, generalisable theoretical model for mtDNA populations during development, allowing the first statistical comparison of proposed bottleneck mechanisms. Using approximate Bayesian computation and mouse data, we find most statistical support for a combination of binomial partitioning of mtDNAs at cell divisions and random mtDNA turnover, meaning that the debated exact magnitude of mtDNA copy number depletion is flexible. New experimental measurements from a wild-derived mtDNA pairing in mice confirm the theoretical predictions of this model. We analytically solve a mathematical description of this mechanism, computing probabilities of mtDNA disease onset, efficacy of clinical sampling strategies, and effects of potential dynamic interventions, thus developing a quantitative and experimentally-supported stochastic theory of the bottleneck. DOI: http://dx.doi.org/10.7554/eLife.07464.001 PMID:26035426

Widespread recombination in published animal mtDNA sequences.

PubMed

Tsaousis, A D; Martin, D P; Ladoukakis, E D; Posada, D; Zouros, E

2005-04-01

Mitochondrial DNA (mtDNA) recombination has been observed in several animal species, but there are doubts as to whether it is common or only occurs under special circumstances. Animal mtDNA sequences retrieved from public databases were unambiguously aligned and rigorously tested for evidence of recombination. At least 30 recombination events were detected among 186 alignments examined. Recombinant sequences were found in invertebrates and vertebrates, including primates. It appears that mtDNA recombination may occur regularly in the animal cell but rarely produces new haplotypes because of homoplasmy. Common animal mtDNA recombination would necessitate a reexamination of phylogenetic and biohistorical inference based on the assumption of clonal mtDNA transmission. Recombination may also have an important role in producing and purging mtDNA mutations and thus in mtDNA-based diseases and senescence.

Minds “At Attention”: Mindfulness Training Curbs Attentional Lapses in Military Cohorts

PubMed Central

Jha, Amishi P.; Morrison, Alexandra B.; Dainer-Best, Justin; Parker, Suzanne; Rostrup, Nina; Stanley, Elizabeth A.

2015-01-01

We investigated the impact of mindfulness training (MT) on attentional performance lapses associated with task-unrelated thought (i.e., mind wandering). Periods of persistent and intensive demands may compromise attention and increase off-task thinking. Here, we investigated if MT may mitigate these deleterious effects and promote cognitive resilience in military cohorts enduring a high-demand interval of predeployment training. To better understand which aspects of MT programs are most beneficial, three military cohorts were examined. Two of the three groups were provided MT. One group received an 8-hour, 8-week variant of Mindfulness-based Mind Fitness Training (MMFT) emphasizing engagement in training exercises (training-focused MT, n = 40), a second group received a didactic-focused variant emphasizing content regarding stress and resilience (didactic-focused MT, n = 40), and the third group served as a no-training control (NTC, n = 24). Sustained Attention to Response Task (SART) performance was indexed in all military groups and a no-training civilian group (CIV, n = 45) before (T1) and after (T2) the MT course period. Attentional performance (measured by A’, a sensitivity index) was lower in NTC vs. CIV at T2, suggesting that performance suffers after enduring a high-demand predeployment interval relative to a similar time period of civilian life. Yet, there were significantly fewer performance lapses in the military cohorts receiving MT relative to NTC, with training-focused MT outperforming didactic-focused MT at T2. From T1 to T2, A’ degraded in NTC and didactic-focused MT but remained stable in training-focused MT and CIV. In sum, while protracted periods of high-demand military training may increase attentional performance lapses, practice-focused MT programs akin to training-focused MT may bolster attentional performance more than didactic-focused programs. As such, training-focused MT programs should be further examined in cohorts experiencing protracted high-demand intervals. PMID:25671579

MT-4 suppresses resistant ovarian cancer growth through targeting tubulin and HSP27.

PubMed

Pai, Hui Chen; Kumar, Sunil; Shen, Chien-Chang; Liou, Jing Ping; Pan, Shiow Lin; Teng, Che Ming

2015-01-01

In this study, the anticancer mechanisms of MT-4 were examined in A2780 and multidrug-resistant NCI-ADR/res human ovarian cancer cell lines. To evaluate the activity of MT-4, we performed in vitro cell viability and cell cycle assays and in vivo xenograft assays. Immunoblotting analysis was carried out to evaluate the effect of MT-4 on ovarian cancer. Tubulin polymerization was determined using a tubulin binding assay. MT-4 (2-Methoxy-5-[2-(3,4,5-trimethoxy-phenyl)-ethyl]-phenol), a derivative of moscatilin, can inhibit both sensitive A2780 and multidrug-resistant NCI-ADR/res cell growth and viability. MT-4 inhibited tubulin polymerization to induce G2/M arrest followed by caspase-mediated apoptosis. Further studies indicated that MT-4 is not a substrate of P-glycoprotein (p-gp). MT-4 also caused G2/M cell cycle arrest, accompanied by the upregulation of cyclin B, p-Thr161 Cdc2/p34, polo-like kinase 1 (PLK1), Aurora kinase B, and phospho-Ser10-histone H3 protein levels. In addition, we found that p38 MAPK pathway activation was involved in MT-4-induced apoptosis. Most importantly, MT-4 also decreased heat shock protein 27 expression and reduced its interaction with caspase-3, which inured cancer cells to chemotherapy resistance. Treatment of cells with SB203580 or overexpression of dominant negative (DN)-p38 or wild-type HSP27 reduced PARP cleavage caused by MT-4. MT-4 induced apoptosis through regulation of p38 and HSP27. Our xenograft models also show the in vivo efficacy of MT-4. MT-4 inhibited both A2780 and NCI-ADR/res cell growth in vitro and in vivo. These findings indicate that MT-4 could be a potential lead compound for the treatment of multidrug-resistant ovarian cancer.

Minds "at attention": mindfulness training curbs attentional lapses in military cohorts.

PubMed

Jha, Amishi P; Morrison, Alexandra B; Dainer-Best, Justin; Parker, Suzanne; Rostrup, Nina; Stanley, Elizabeth A

2015-01-01

We investigated the impact of mindfulness training (MT) on attentional performance lapses associated with task-unrelated thought (i.e., mind wandering). Periods of persistent and intensive demands may compromise attention and increase off-task thinking. Here, we investigated if MT may mitigate these deleterious effects and promote cognitive resilience in military cohorts enduring a high-demand interval of predeployment training. To better understand which aspects of MT programs are most beneficial, three military cohorts were examined. Two of the three groups were provided MT. One group received an 8-hour, 8-week variant of Mindfulness-based Mind Fitness Training (MMFT) emphasizing engagement in training exercises (training-focused MT, n = 40), a second group received a didactic-focused variant emphasizing content regarding stress and resilience (didactic-focused MT, n = 40), and the third group served as a no-training control (NTC, n = 24). Sustained Attention to Response Task (SART) performance was indexed in all military groups and a no-training civilian group (CIV, n = 45) before (T1) and after (T2) the MT course period. Attentional performance (measured by A', a sensitivity index) was lower in NTC vs. CIV at T2, suggesting that performance suffers after enduring a high-demand predeployment interval relative to a similar time period of civilian life. Yet, there were significantly fewer performance lapses in the military cohorts receiving MT relative to NTC, with training-focused MT outperforming didactic-focused MT at T2. From T1 to T2, A' degraded in NTC and didactic-focused MT but remained stable in training-focused MT and CIV. In sum, while protracted periods of high-demand military training may increase attentional performance lapses, practice-focused MT programs akin to training-focused MT may bolster attentional performance more than didactic-focused programs. As such, training-focused MT programs should be further examined in cohorts experiencing protracted high-demand intervals.

The Strictly Aerobic Yeast Yarrowia lipolytica Tolerates Loss of a Mitochondrial DNA-Packaging Protein

PubMed Central

Bakkaiova, Jana; Arata, Kosuke; Matsunobu, Miki; Ono, Bungo; Aoki, Tomoyo; Lajdova, Dana; Nebohacova, Martina; Nosek, Jozef; Miyakawa, Isamu

2014-01-01

Mitochondrial DNA (mtDNA) is highly compacted into DNA-protein structures termed mitochondrial nucleoids (mt-nucleoids). The key mt-nucleoid components responsible for mtDNA condensation are HMG box-containing proteins such as mammalian mitochondrial transcription factor A (TFAM) and Abf2p of the yeast Saccharomyces cerevisiae. To gain insight into the function and organization of mt-nucleoids in strictly aerobic organisms, we initiated studies of these DNA-protein structures in Yarrowia lipolytica. We identified a principal component of mt-nucleoids in this yeast and termed it YlMhb1p (Y. lipolytica mitochondrial HMG box-containing protein 1). YlMhb1p contains two putative HMG boxes contributing both to DNA binding and to its ability to compact mtDNA in vitro. Phenotypic analysis of a Δmhb1 strain lacking YlMhb1p resulted in three interesting findings. First, although the mutant exhibits clear differences in mt-nucleoids accompanied by a large decrease in the mtDNA copy number and the number of mtDNA-derived transcripts, its respiratory characteristics and growth under most of the conditions tested are indistinguishable from those of the wild-type strain. Second, our results indicate that a potential imbalance between subunits of the respiratory chain encoded separately by nuclear DNA and mtDNA is prevented at a (post)translational level. Third, we found that mtDNA in the Δmhb1 strain is more prone to mutations, indicating that mtHMG box-containing proteins protect the mitochondrial genome against mutagenic events. PMID:24972935

Fibromyalgia--a syndrome associated with decreased nocturnal melatonin secretion.

PubMed

Wikner, J; Hirsch, U; Wetterberg, L; Röjdmark, S

1998-08-01

Most patients with fibromyalgic syndrome (FMS) complain of sleep disturbances, fatigue, and pain. These symptoms might be a consequence of changed melatonin (MT) secretion, since MT is known to have sleep promoting properties. Moreover, serum concentrations of two MT precursors (tryptophan and serotonin)--affecting both sleep and pain perception--appear to be low in patients with FMS. Therefore, the objective of this investigation was to study whether serum MT (s-MT) level is also low in these patients. Eight patients with FMS and 8 healthy sex-, BMI-, and age-matched controls were included in the study. s-MT concentrations were determined every second hour between 1800 and 0800 h. Urine was collected between 2200 and 0700 h for determination of urinary MT excretion. To evaluate total MT secretion between 1800 and 0800 h and MT secretion during the hours of darkness (between 23 and 07 h) individual MT areas under the curve (AUC) were calculated and expressed as group means. The FMS patients had a 31% lower MT secretion than healthy subjects during the hours of darkness (MT AUC 2300-0700 h (mean +/- SEM): 1.70 +/- 0.17 vs 2.48 +/- 0.38 nmol/l; P < 0.05). Also the s-MT peak value was significantly lower in the patient group: 0.28 +/- 0.03 vs 0.44 +/- 0.06 nmol/l; P < 0.05). Patients with fibromyalgic syndrome have a lower melatonin secretion during the hours of darkness than healthy subjects. This may contribute to impaired sleep at night, fatigue during the day, and changed pain perception.

Evidence of animal mtDNA recombination between divergent populations of the potato cyst nematode Globodera pallida.

PubMed

Hoolahan, Angelique H; Blok, Vivian C; Gibson, Tracey; Dowton, Mark

2012-03-01

Recombination is typically assumed to be absent in animal mitochondrial genomes (mtDNA). However, the maternal mode of inheritance means that recombinant products are indistinguishable from their progenitor molecules. The majority of studies of mtDNA recombination assess past recombination events, where patterns of recombination are inferred by comparing the mtDNA of different individuals. Few studies assess contemporary mtDNA recombination, where recombinant molecules are observed as direct mosaics of known progenitor molecules. Here we use the potato cyst nematode, Globodera pallida, to investigate past and contemporary recombination. Past recombination was assessed within and between populations of G. pallida, and contemporary recombination was assessed in the progeny of experimental crosses of these populations. Breeding of genetically divergent organisms may cause paternal mtDNA leakage, resulting in heteroplasmy and facilitating the detection of recombination. To assess contemporary recombination we looked for evidence of recombination between the mtDNA of the parental populations within the mtDNA of progeny. Past recombination was detected between a South American population and several UK populations of G. pallida, as well as between two South American populations. This suggests that these populations may have interbred, paternal mtDNA leakage occurred, and the mtDNA of these populations subsequently recombined. This evidence challenges two dogmas of animal mtDNA evolution; no recombination and maternal inheritance. No contemporary recombination between the parental populations was detected in the progeny of the experimental crosses. This supports current arguments that mtDNA recombination events are rare. More sensitive detection methods may be required to adequately assess contemporary mtDNA recombination in animals.

Mitochondrial tRNA cleavage by tRNA-targeting ribonuclease causes mitochondrial dysfunction observed in mitochondrial disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, Tetsuhiro, E-mail: atetsu@mail.ecc.u-tokyo.ac.jp; Shimizu, Ayano; Takahashi, Kazutoshi

2014-08-15

Highlights: • MTS-tagged ribonuclease was translocated successfully to the mitochondrial matrix. • MTS-tagged ribonuclease cleaved mt tRNA and reduced COX activity. • Easy and reproducible method of inducing mt tRNA dysfunction. - Abstract: Mitochondrial DNA (mtDNA) is a genome possessed by mitochondria. Since reactive oxygen species (ROS) are generated during aerobic respiration in mitochondria, mtDNA is commonly exposed to the risk of DNA damage. Mitochondrial disease is caused by mitochondrial dysfunction, and mutations or deletions on mitochondrial tRNA (mt tRNA) genes are often observed in mtDNA of patients with the disease. Hence, the correlation between mt tRNA activity and mitochondrialmore » dysfunction has been assessed. Then, cybrid cells, which are constructed by the fusion of an enucleated cell harboring altered mtDNA with a ρ{sup 0} cell, have long been used for the analysis due to difficulty in mtDNA manipulation. Here, we propose a new method that involves mt tRNA cleavage by a bacterial tRNA-specific ribonuclease. The ribonuclease tagged with a mitochondrial-targeting sequence (MTS) was successfully translocated to the mitochondrial matrix. Additionally, mt tRNA cleavage, which resulted in the decrease of cytochrome c oxidase (COX) activity, was observed.« less

Metallothionein expression in canine and feline mammary and melanotic tumours.

PubMed

Dincer, Z; Jasani, B; Haywood, S; Mullins, J E; Fuentealba, I C

2001-01-01

Moderate to strong immunohistochemical metallothionein (MT) positivity (MT expression) is associated with a poor prognosis in some human tumours. The aim of this study was to determine MT expression in mammary tumours and cutaneous melanomas in dogs and cats. Canine (67) and feline (47) mammary tumours, and cutaneous melanomas (canine 40, feline 26) were immunolabelled with MT monoclonal antibody E9. The overall incidence of MT expression of these tumours was similar to that observed in various human neoplasms. However, a striking interspecies difference was detected. In dogs, MT expression occurred in 100% of benign and 57% of malignant mammary tumours. In cats, however, 30% of malignant mammary tumours expressed MT but benign mammary tumours and cases of fibroadenomatous hyperplasia did not. Moderate to strong MT immunoreactivity was detected in 30% of benign and 25% of malignant cutaneous melanomas in dogs, and in 6% of malignant melanomas in cats. The findings in feline mammary tumours resembled findings reported in human breast cancer, but the cause of tumour-associated MT expression is unknown. Studies are in progress to determine whether the MT state (apo [metal-free] or holo [metal-bound]) accounts for the paradoxical association of MT expression with individual types of tumours and the animal species in which they arise. Copyright Harcourt Publishers Ltd.

Mitochondrial genome-maintaining activity of mouse mitochondrial transcription factor A and its transcript isoform in Saccharomyces cerevisiae.

PubMed

Yoon, Young Geol; Koob, Michael D; Yoo, Young Hyun

2011-09-15

Mitochondrial transcription factor A (Tfam) binds to and organizes mitochondrial DNA (mtDNA) genome into a mitochondrial nucleoid (mt-nucleoid) structure, which is necessary for mtDNA transcription and maintenance. Here, we demonstrate the mtDNA-organizing activity of mouse Tfam and its transcript isoform (Tfam(iso)), which has a smaller high-mobility group (HMG)-box1 domain, using a yeast model system that contains a deletion of the yeast homolog of mouse Tfam protein, Abf2p. When the mouse Tfam genes were introduced into the ABF2 locus of yeast genome, the corresponding mouse proteins, Tfam and Tfam(iso), can functionally replace the yeast Abf2p and support mtDNA maintenance and mitochondrial biogenesis in yeast. Growth properties, mtDNA content and mitochondrial protein levels of genes encoded in the mtDNA were comparable in the strains expressing mouse proteins and the wild-type yeast strain, indicating that the proteins have robust mtDNA-maintaining and -expressing function in yeast mitochondria. These results imply that the mtDNA-organizing activities of the mouse mt-nucleoid proteins are structurally and evolutionary conserved, thus they can maintain the mtDNA of distantly related and distinctively different species, such as yeast. Copyright © 2011 Elsevier B.V. All rights reserved.

Mitochondrial DNA heteroplasmy in Candida glabrata after mitochondrial transformation.

PubMed

Zhou, Jingwen; Liu, Liming; Chen, Jian

2010-05-01

Genetic manipulation of mitochondrial DNA (mtDNA) is the most direct method for investigating mtDNA, but until now, this has been achieved only in the diploid yeast Saccharomyces cerevisiae. In this study, the ATP6 gene on mtDNA of the haploid yeast Candida glabrata (Torulopsis glabrata) was deleted by biolistic transformation of DNA fragments with a recoded ARG8(m) mitochondrial genetic marker, flanked by homologous arms to the ATP6 gene. Transformants were identified by arginine prototrophy. However, in the transformants, the original mtDNA was not lost spontaneously, even under arginine selective pressure. Moreover, the mtDNA transformants selectively lost the transformed mtDNA under aerobic conditions. The mtDNA heteroplasmy in the transformants was characterized by PCR, quantitative PCR, and Southern blotting, showing that the heteroplasmy was relatively stable in the absence of arginine. Aerobic conditions facilitated the loss of the original mtDNA, and anaerobic conditions favored loss of the transformed mtDNA. Moreover, detailed investigations showed that increases in reactive oxygen species in mitochondria lacking ATP6, along with their equal cell division, played important roles in determining the dynamics of heteroplasmy. Based on our analysis of mtDNA heteroplasmy in C. glabrata, we were able to generate homoplasmic Deltaatp6 mtDNA strains.

Presequence-Independent Mitochondrial Import of DNA Ligase Facilitates Establishment of Cell Lines with Reduced mtDNA Copy Number

PubMed Central

Spadafora, Domenico; Kozhukhar, Natalia; Alexeyev, Mikhail F.

2016-01-01

Due to the essential role played by mitochondrial DNA (mtDNA) in cellular physiology and bioenergetics, methods for establishing cell lines with altered mtDNA content are of considerable interest. Here, we report evidence for the existence in mammalian cells of a novel, low- efficiency, presequence-independent pathway for mitochondrial protein import, which facilitates mitochondrial uptake of such proteins as Chlorella virus ligase (ChVlig) and Escherichia coli LigA. Mouse cells engineered to depend on this pathway for mitochondrial import of the LigA protein for mtDNA maintenance had severely (up to >90%) reduced mtDNA content. These observations were used to establish a method for the generation of mouse cell lines with reduced mtDNA copy number by, first, transducing them with a retrovirus encoding LigA, and then inactivating in these transductants endogenous Lig3 with CRISPR-Cas9. Interestingly, mtDNA depletion to an average level of one copy per cell proceeds faster in cells engineered to maintain mtDNA at low copy number. This makes a low-mtDNA copy number phenotype resulting from dependence on mitochondrial import of DNA ligase through presequence-independent pathway potentially useful for rapidly shifting mtDNA heteroplasmy through partial mtDNA depletion. PMID:27031233

Subsurface Structure Interpretation Beneath of Mt. Pandan Based on Gravity Data

NASA Astrophysics Data System (ADS)

Santoso, D.; Wahyudi, E. J.; Alawiyah, S.; Nugraha, A. D.; Widiyantoro, S.; Kadir, W. G. A.; Supendi, P.; Wiyono, S.; Zulkafriza

2017-04-01

Mt. Pandan is one of the volcano that state as dormant volcano. On the other hand, Smyth et al. (2008) defined that Mt. Pandan is an active volcano. This volcano is apart a volcanic chain in Java island which is trending east-west along the island. This volcanic chain known as present day volcanic arc. Mt. Wilis is located in the south and it relatively much bigger compare to Mt. Pandan. There were earthquakes activity experienced in the surrounding Mt. Pandan area in the past several years. This event is interesting, because Mt. Pandan is not classify as the active volcano according to the list of volcanoes in Indonesia. On the otherhand Smyth et. al. (2008) mentioned that G. Pandan as modern volcanic which is located in Kendeng Zone of East Java. Gravity measurement around Mt. Pandan area was done in order to understand subsurface structure of Mt. Pandan. Gravity interpretation results shows that there is a low density structure beneath Mt. Pandan. It could be interpreted as existing of magma body below the surface. Some indication of submagmatic activities were found as hot spring and warm ground. Therefore it could be concluded that there is a possibility of magmatic activity below the Mt. Pandan.

Nose-to-brain transport of melatonin from polymer gel suspensions: a microdialysis study in rats.

PubMed

Jayachandra Babu, R; Dayal, Pankaj Patrick; Pawar, Kasturi; Singh, Mandip

2011-11-01

Exogenous melatonin (MT) has significant neuroprotective roles in Alzheimer's and Parkinson's diseases. This study investigates the delivery MT to brain via nasal route as a polymeric gel suspension using central brain microdialysis in anesthetized rats. Micronized MT suspensions using polymers [carbopol, carboxymethyl cellulose (CMC)] and polyethylene glycol 400 (PEG400) were prepared and characterized for nasal administration. In vitro permeation of the formulations was measured across a three-dimensional tissue culture model EpiAirway(™). The central brain delivery into olfactory bulb of nasally administered MT gel suspensions was studied using brain microdialysis in male Wistar rats. The MT content of microdialysis samples was analyzed by high performance liquid chromatography (HPLC) using electrochemical detection. The nose-to-brain delivery of MT formulations was compared with intravenously administered MT solution. MT suspensions in carbopol and CMC vehicles have shown significantly higher permeability across Epiairway(™) as compared to control, PEG400 (P < 0.05). The brain (olfactory bulb) levels of MT after intranasal administration were 9.22, 6.77 and 4.04-fold higher for carbopol, CMC and PEG400, respectively, than that of intravenous MT in rats. In conclusion, microdialysis studies demonstrated increased brain levels of MT via nasal administration in rats.

Nose-to-brain transport of melatonin from polymer gel suspensions: a microdialysis study in rats

PubMed Central

Babu, R. Jayachandra; Dayal, Pankaj Patrick; Pawar, Kasturi; Singh, Mandip

2012-01-01

Purpose Exogenous melatonin (MT) has significant neuroprotective roles in Alzheimer’s and Parkinson’s diseases. This study investigates the delivery MT to brain via nasal route as a polymeric gel suspension using central brain microdialysis in anesthetized rats. Methods Micronized MT suspensions using polymers [carbopol, carboxymethyl cellulose (CMC)] and polyethylene glycol 400 (PEG400) were prepared and characterized for nasal administration. In vitro permeation of the formulations was measured across a three-dimensional tissue culture model EpiAirway™. The central brain delivery into olfactory bulb of nasally administered MT gel suspensions was studied using brain microdialysis in male Wistar rats. The MT content of microdialysis samples was analyzed by high performance liquid chromatography (HPLC) using electrochemical detection. The nose-to-brain delivery of MT formulations was compared with intravenously administered MT solution. Results MT suspensions in carbopol and CMC vehicles have shown significantly higher permeability across Epiairway™ as compared to control, PEG400 (P < 0.05). The brain (olfactory bulb) levels of MT after intranasal administration were 9.22, 6.77 and 4.04-fold higher for carbopol, CMC and PEG400, respectively, than that of intravenous MT in rats. In conclusion, microdialysis studies demonstrated increased brain levels of MT via nasal administration in rats. PMID:21428693

Cytoplasmic Nucleation and Atypical Branching Nucleation Generate Endoplasmic Microtubules in Physcomitrella patens[OPEN

PubMed Central

Nakaoka, Yuki; Kimura, Akatsuki; Tani, Tomomi; Goshima, Gohta

2015-01-01

The mechanism underlying microtubule (MT) generation in plants has been primarily studied using the cortical MT array, in which fixed-angled branching nucleation and katanin-dependent MT severing predominate. However, little is known about MT generation in the endoplasm. Here, we explored the mechanism of endoplasmic MT generation in protonemal cells of Physcomitrella patens. We developed an assay that utilizes flow cell and oblique illumination fluorescence microscopy, which allowed visualization and quantification of individual MT dynamics. MT severing was infrequently observed, and disruption of katanin did not severely affect MT generation. Branching nucleation was observed, but it showed markedly variable branch angles and was occasionally accompanied by the transport of nucleated MTs. Cytoplasmic nucleation at seemingly random locations was most frequently observed and predominated when depolymerized MTs were regrown. The MT nucleator γ-tubulin was detected at the majority of the nucleation sites, at which a single MT was generated in random directions. When γ-tubulin was knocked down, MT generation was significantly delayed in the regrowth assay. However, nucleation occurred at a normal frequency in steady state, suggesting the presence of a γ-tubulin-independent backup mechanism. Thus, endoplasmic MTs in this cell type are generated in a less ordered manner, showing a broader spectrum of nucleation mechanisms in plants. PMID:25616870

Organization and dynamics of yeast mitochondrial nucleoids

PubMed Central

MIYAKAWA, Isamu

2017-01-01

Mitochondrial DNA (mtDNA) is packaged by association with specific proteins in compact DNA-protein complexes named mitochondrial nucleoids (mt-nucleoids). The budding yeast Saccharomyces cerevisiae is able to grow either aerobically or anaerobically. Due to this characteristic, S. cerevisiae has been extensively used as a model organism to study genetics, morphology and biochemistry of mitochondria for a long time. Mitochondria of S. cerevisiae frequently fuse and divide, and perform dynamic morphological changes depending on the culture conditions and the stage of life cycle of the yeast cells. The mt-nucleoids also dynamically change their morphology, accompanying morphological changes of mitochondria. The mt-nucleoids have been isolated morphologically intact and functional analyses of mt-nucleoid proteins have been extensively performed. These studies have revealed that the functions of mt-nucleoid proteins are essential for maintenance of mtDNA. The aims of this review are to summarize the history on the research of yeast mt-nucleoids as well as recent findings on the organization of the mt-nucleoids and mitochondrial dynamics. PMID:28496055

A novel noncovalent complex of chorismate mutase and DAHP synthase from Mycobacterium tuberculosis: protein purification, crystallization and X-ray diffraction analysis

PubMed Central

Ökvist, Mats; Sasso, Severin; Roderer, Kathrin; Kast, Peter; Krengel, Ute

2009-01-01

Chorismate mutase catalyzes a key step in the shikimate-biosynthetic pathway and hence is an essential enzyme in bacteria, plants and fungi. Mycobacterium tuberculosis contains two chorismate mutases, a secreted and an intracellular one, the latter of which (MtCM; Rv0948c; 90 amino-acid residues; 10 kDa) is the subject of this work. Here are reported the gene expression, purification and crystallization of MtCM alone and of its complex with another shikimate-pathway enzyme, DAHP synthase (MtDS; Rv2178c; 472 amino-acid residues; 52 kDa), which has been shown to enhance the catalytic efficiency of MtCM. The MtCM–MtDS complex represents the first noncovalent enzyme complex from the common shikimate pathway to be structurally characterized. Soaking experiments with a transition-state analogue are also reported. The crystals of MtCM and the MtCM–MtDS complex diffracted to 1.6 and 2.1 Å resolution, respectively. PMID:19851019

Steroid androgen 17α-methyltestosterone induces malformations and biochemical alterations in zebrafish embryos.

PubMed

Rivero-Wendt, Carla Letícia Gediel; Oliveira, Rhaul; Monteiro, Marta Sofia; Domingues, Inês; Soares, Amadeu Mortágua Velho Maia; Grisolia, Cesar Koppe

2016-06-01

The synthetic androgen 17α-methyltestosterone is widely used in fish aquaculture for sex reversion of female individuals. Little is known about the amount of MT residues reaching the aquatic environment and further impacts in non-target organisms, including fish early-life stages. Thus, in this work, zebrafish embryos were exposed to two forms of 17α-methyltestosterone: the pure compound (MT) and a formulation commonly used in Brazil (cMT). For MT, a 96h-LC50 of 10.09mg/l was calculated. MT also affected embryo development inducing tail malformations, edemas, abnormal development of the head, and hatching delay. At biochemical level MT inhibited vitellogenin (VTG) and inhibited cholinesterase and lactate dehydrogenase. cMT elicited similar patterns of toxicity as the pure compound (MT). Effects reported in this study suggest a potential environmental risk of MT, especially since the VTG effects occurred at environmental relevant concentrations (0.004mg/l). Copyright © 2016 Elsevier B.V. All rights reserved.

Functions of the high mobility group protein, Abf2p, in mitochondrial DNA segregation, recombination and copy number in Saccharomyces cerevisiae.

PubMed

Zelenaya-Troitskaya, O; Newman, S M; Okamoto, K; Perlman, P S; Butow, R A

1998-04-01

Previous studies have established that the mitochondrial high mobility group (HMG) protein, Abf2p, of Saccharomyces cerevisiae influences the stability of wild-type (rho+) mitochondrial DNA (mtDNA) and plays an important role in mtDNA organization. Here we report new functions for Abf2p in mtDNA transactions. We find that in homozygous deltaabf2 crosses, the pattern of sorting of mtDNA and mitochondrial matrix protein is altered, and mtDNA recombination is suppressed relative to homozygous ABF2 crosses. Although Abf2p is known to be required for the maintenance of mtDNA in rho+ cells growing on rich dextrose medium, we find that it is not required for the maintenance of mtDNA in p cells grown on the same medium. The content of both rho+ and rho- mtDNAs is increased in cells by 50-150% by moderate (two- to threefold) increases in the ABF2 copy number, suggesting that Abf2p plays a role in mtDNA copy control. Overproduction of Abf2p by > or = 10-fold from an ABF2 gene placed under control of the GAL1 promoter, however, leads to a rapid loss of rho+ mtDNA and a quantitative conversion of rho+ cells to petites within two to four generations after a shift of the culture from glucose to galactose medium. Overexpression of Abf2p in rho- cells also leads to a loss of mtDNA, but at a slower rate than was observed for rho+ cells. The mtDNA instability phenotype is related to the DNA-binding properties of Abf2p because a mutant Abf2p that contains mutations in residues of both HMG box domains known to affect DNA binding in vitro, and that binds poorly to mtDNA in vivo, complements deltaabf2 cells only weakly and greatly lessens the effect of overproduction on mtDNA instability. In vivo binding was assessed by colocalization to mtDNA of fusions between mutant or wild-type Abf2p and green fluorescent protein. These findings are discussed in the context of a model relating mtDNA copy number control and stability to mtDNA recombination.

Lunar rover technology demonstrations with Dante and Ratler

NASA Technical Reports Server (NTRS)

Krotkov, Eric; Bares, John; Katragadda, Lalitesh; Simmons, Reid; Whittaker, Red

1994-01-01

Carnegie Mellon University has undertaken a research, development, and demonstration program to enable a robotic lunar mission. The two-year mission scenario is to traverse 1,000 kilometers, revisiting the historic sites of Apollo 11, Surveyor 5, Ranger 8, Apollo 17, and Lunokhod 2, and to return continuous live video amounting to more than 11 terabytes of data. Our vision blends autonomously safeguarded user driving with autonomous operation augmented with rich visual feedback, in order to enable facile interaction and exploration. The resulting experience is intended to attract mass participation and evoke strong public interest in lunar exploration. The encompassing program that forwards this work is the Lunar Rover Initiative (LRI). Two concrete technology demonstration projects currently advancing the Lunar Rover Initiative are: (1) The Dante/Mt. Spurr project, which, at the time of this writing, is sending the walking robot Dante to explore the Mt. Spurr volcano, in rough terrain that is a realistic planetary analogue. This project will generate insights into robot system robustness in harsh environments, and into remote operation by novices; and (2) The Lunar Rover Demonstration project, which is developing and evaluating key technologies for navigation, teleoperation, and user interfaces in terrestrial demonstrations. The project timetable calls for a number of terrestrial traverses incorporating teleoperation and autonomy including natural terrain this year, 10 km in 1995. and 100 km in 1996. This paper will discuss the goals of the Lunar Rover Initiative and then focus on the present state of the Dante/Mt. Spurr and Lunar Rover Demonstration projects.

Lung excision of non-small-cell lung cancer leaves cancer cells in residual lobe: cytological detection using pulmonary vein blood.

PubMed

Sawabata, Noriyoshi; Funaki, Soichiro; Shintani, Yasushi; Okumura, Meinosin

2016-02-01

Lung excision to treat non-small-cell lung cancer (NSCLC) is associated with a worse prognosis when compared with a lobectomy. Cancer relapse may be caused by tumour cells remaining in the residual lobe, the possibility of dislodged cancer cells in the residual lobe is assessed using pulmonary vein blood (PVB) from the resected lung. Twenty-eight patients with pathological stage I NSCLC who underwent lung excision followed by a lobectomy were evaluated according to the status of isolated tumour cells (ITCs) (origin of circulating tumour cells) in PVB from the resected lobe. Survival was also assessed according to the status of ITCs. The rate of ITC presence was 60.7% and depended on margin distance/tumour size (M/T) with a threshold of 1.0-30.8% (4/13) in M/T greater than or equal to 1.0 and 86.7% (13/15) in M/T smaller than 1.0 (P = 0.001). PVB-ITC status was no ITCs (N) in 11 (39.3%), only singular cells (S) in 13 (50.0%) and clustered cells (C) in 4 (14.3%). In addition, the survival status of patients with clustered cells was exclusively wrong. After pulmonary excision for lung cancer, tumour cells remain in the residual lobe and the morphology of which may indicate recurrence. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Germline mitochondrial DNA mutations aggravate ageing and can impair brain development.

PubMed

Ross, Jaime M; Stewart, James B; Hagström, Erik; Brené, Stefan; Mourier, Arnaud; Coppotelli, Giuseppe; Freyer, Christoph; Lagouge, Marie; Hoffer, Barry J; Olson, Lars; Larsson, Nils-Göran

2013-09-19

Ageing is due to an accumulation of various types of damage, and mitochondrial dysfunction has long been considered to be important in this process. There is substantial sequence variation in mammalian mitochondrial DNA (mtDNA), and the high mutation rate is counteracted by different mechanisms that decrease maternal transmission of mutated mtDNA. Despite these protective mechanisms, it is becoming increasingly clear that low-level mtDNA heteroplasmy is quite common and often inherited in humans. We designed a series of mouse mutants to investigate the extent to which inherited mtDNA mutations can contribute to ageing. Here we report that maternally transmitted mtDNA mutations can induce mild ageing phenotypes in mice with a wild-type nuclear genome. Furthermore, maternally transmitted mtDNA mutations lead to anticipation of reduced fertility in mice that are heterozygous for the mtDNA mutator allele (PolgA(wt/mut)) and aggravate premature ageing phenotypes in mtDNA mutator mice (PolgA(mut/mut)). Unexpectedly, a combination of maternally transmitted and somatic mtDNA mutations also leads to stochastic brain malformations. Our findings show that a pre-existing mutation load will not only allow somatic mutagenesis to create a critically high total mtDNA mutation load sooner but will also increase clonal expansion of mtDNA mutations to enhance the normally occurring mosaic respiratory chain deficiency in ageing tissues. Our findings suggest that maternally transmitted mtDNA mutations may have a similar role in aggravating aspects of normal human ageing.

Anchoring plant metallothioneins to the inner face of the plasma membrane of Saccharomyces cerevisiae cells leads to heavy metal accumulation.

PubMed

Ruta, Lavinia Liliana; Lin, Ya-Fen; Kissen, Ralph; Nicolau, Ioana; Neagoe, Aurora Daniela; Ghenea, Simona; Bones, Atle M; Farcasanu, Ileana Cornelia

2017-01-01

In this study we engineered yeast cells armed for heavy metal accumulation by targeting plant metallothioneins to the inner face of the yeast plasma membrane. Metallothioneins (MTs) are cysteine-rich proteins involved in the buffering of excess metal ions, especially Cu(I), Zn(II) or Cd(II). The cDNAs of seven Arabidopsis thaliana MTs (AtMT1a, AtMT1c, AtMT2a, AtMT2b, AtMT3, AtMT4a and AtMT4b) and four Noccaea caerulescens MTs (NcMT1, NcMT2a, NcMT2b and NcMT3) were each translationally fused to the C-terminus of a myristoylation green fluorescent protein variant (myrGFP) and expressed in Saccharomyces cerevisiae cells. The myrGFP cassette introduced a yeast myristoylation sequence which allowed directional targeting to the cytosolic face of the plasma membrane along with direct monitoring of the intracellular localization of the recombinant protein by fluorescence microscopy. The yeast strains expressing plant MTs were investigated against an array of heavy metals in order to identify strains which exhibit the (hyper)accumulation phenotype without developing toxicity symptoms. Among the transgenic strains which could accumulate Cu(II), Zn(II) or Cd(II), but also non-canonical metal ions, such as Co(II), Mn(II) or Ni(II), myrGFP-NcMT3 qualified as the best candidate for bioremediation applications, thanks to the robust growth accompanied by significant accumulative capacity.

Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease

PubMed Central

Nicholls, Thomas J.; Zsurka, Gábor; Peeva, Viktoriya; Schöler, Susanne; Szczesny, Roman J.; Cysewski, Dominik; Reyes, Aurelio; Kornblum, Cornelia; Sciacco, Monica; Moggio, Maurizio; Dziembowski, Andrzej; Kunz, Wolfram S.; Minczuk, Michal

2014-01-01

MGME1, also known as Ddk1 or C20orf72, is a mitochondrial exonuclease found to be involved in the processing of mitochondrial DNA (mtDNA) during replication. Here, we present detailed insights on the role of MGME1 in mtDNA maintenance. Upon loss of MGME1, elongated 7S DNA species accumulate owing to incomplete processing of 5′ ends. Moreover, an 11-kb linear mtDNA fragment spanning the entire major arc of the mitochondrial genome is generated. In contrast to control cells, where linear mtDNA molecules are detectable only after nuclease S1 treatment, the 11-kb fragment persists in MGME1-deficient cells. In parallel, we observed characteristic mtDNA duplications in the absence of MGME1. The fact that the breakpoints of these mtDNA rearrangements do not correspond to either classical deletions or the ends of the linear 11-kb fragment points to a role of MGME1 in processing mtDNA ends, possibly enabling their repair by homologous recombination. In agreement with its functional involvement in mtDNA maintenance, we show that MGME1 interacts with the mitochondrial replicase PolgA, suggesting that it is a constituent of the mitochondrial replisome, to which it provides an additional exonuclease activity. Thus, our results support the viewpoint that MGME1-mediated mtDNA processing is essential for faithful mitochondrial genome replication and might be required for intramolecular recombination of mtDNA. PMID:24986917

Reduced mitochondrial DNA content associates with poor prognosis of prostate cancer in African American men.

PubMed

Koochekpour, Shahriar; Marlowe, Timothy; Singh, Keshav K; Attwood, Kristopher; Chandra, Dhyan

2013-01-01

Reduction or depletion of mitochondrial DNA (mtDNA) has been associated with cancer progression. Although imbalanced mtDNA content is known to occur in prostate cancer, differences in mtDNA content between African American (AA) and Caucasian American (CA) men are not defined. We provide the first evidence that tumors in AA men possess reduced level of mtDNA compared to CA men. The median tumor mtDNA content was reduced in AA men. mtDNA content was also reduced in normal prostate tissues of AA men compared to CA men, suggesting a possible predisposition to cancer in AA men. mtDNA content was also reduced in benign prostatic hyperplasia (BPH) tissue from AA men. Tumor and BPH tissues from patients ≥ 60 years of age possess reduced mtDNA content compared to patients <60 years of age. In addition, mtDNA content was higher in normal tissues from patients with malignant T3 stage disease compared to patients with T2 stage disease. mtDNA levels in matched normal prostate tissues were nearly doubled in Gleason grade of >7 compared to ≤ 7, whereas reduced mtDNA content was observed in tumors of Gleason grade >7 compared to ≤ 7. Together, our data suggest that AA men possess lower mtDNA levels in normal and tumor tissues compared to CA men, which could contribute to higher risk and more aggressive prostate cancer in AA men.

Washington Camp-A New Site for TSU Astronomy

NASA Astrophysics Data System (ADS)

Wade, Montanez A.

1997-02-01

The astronomy research program at Tennessee State University began in the Center of Excellence in Information Systems in 1988 with a grant from Marshall Space Flight Center. The initial research was to expand the investigation of Dr. D. S. Hall of Vanderbilt University on the behavior of chromospherically active (CA) stars utilizing automatic photometric telescopes (APT's)located in the southern Arizonan desert at the Smithsonian Institution's Mt. Hopkins Facility (Fred Whipple Observatory). The APT's were and are operated by Fairborn Observatory, a non-profit organization. Over the years the TSU program significantly expanded and by 1996 CASS astronomers managed four APT's at the Mt. Hopkins site: Fairborn 10-in, SAO/TSU 30- in, the Vanderbilt/TSU 16-in, and the TSU/SAO 32-in. In addition to CA star research, the program now includes observation of solar duplicates to better understand the Sun-climate connection, investigation of magnetic activity in cool stars, and verification of the existence of extra-solar planets. Observing schemes are programmed in Nashville and data are retrieved from the Arizona site via the Internet. With CASS funding TSU has under construction a 2-m automatic spectroscopic telescope (AST) and a 24-in automatic imaging telescope (AIT). Anticipating this expansion, Fairborn Observatory located a 40 acre site in Washington Camp, AZ to build its own expanded facility. This paper will present a brief history of the TSU astrophysics program including a cursory description of the research areas, the instrumentation utilized in data acquisition, and a description of the facilities.

Scale-invariant instantons and the complete lifetime of the standard model

NASA Astrophysics Data System (ADS)

Andreassen, Anders; Frost, William; Schwartz, Matthew D.

2018-03-01

In a classically scale-invariant quantum field theory, tunneling rates are infrared divergent due to the existence of instantons of any size. While one expects such divergences to be resolved by quantum effects, it has been unclear how higher-loop corrections can resolve a problem appearing already at one loop. With a careful power counting, we uncover a series of loop contributions that dominate over the one-loop result and sum all the necessary terms. We also clarify previously incomplete treatments of related issues pertaining to global symmetries, gauge fixing, and finite mass effects. In addition, we produce exact closed-form solutions for the functional determinants over scalars, fermions, and vector bosons around the scale-invariant bounce, demonstrating manifest gauge invariance in the vector case. With these problems solved, we produce the first complete calculation of the lifetime of our Universe: 1 0139 years . With 95% confidence, we expect our Universe to last more than 1 058 years . The uncertainty is part experimental uncertainty on the top quark mass and on αs and part theory uncertainty from electroweak threshold corrections. Using our complete result, we provide phase diagrams in the mt/mh and the mt/αs planes, with uncertainty bands. To rule out absolute stability to 3 σ confidence, the uncertainty on the top quark pole mass would have to be pushed below 250 MeV or the uncertainty on αs(mZ) pushed below 0.00025.

METHYLATION OF ARSENIC BY RECOMBINANT HUMAN AS3MT/287M AND AS3MT/287T POLYMORPHS

EPA Science Inventory

Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). AS3MT polymorphism is, in part, responsible for interindividual differences in iAs metabolism. AS3MT/M287T polymorphism that is found in ~ 10% of C...

Examining Dark Triad traits in relation to mental toughness and physical activity in young adults.

PubMed

Sabouri, Sarah; Gerber, Markus; Sadeghi Bahmani, Dena; Lemola, Sakari; Clough, Peter J; Kalak, Nadeem; Shamsi, Mahin; Holsboer-Trachsler, Edith; Brand, Serge

2016-01-01

The Dark Triad (DT) describes a set of three closely related personality traits: Machiavellianism, narcissism, and psychopathy. Mental toughness (MT) refers to a psychological construct combining confidence, commitment, control, and challenge. High MT is related to greater physical activity (PA) and, relative to men, women have lower MT scores. The aims of the present study were 1) to investigate the association between DT, MT, and PA, and 2) to compare the DT, MT, and PA scores of men and women. A total of 341 adults (M=29 years; 51.6% women; range: 18-37 years) took part in the study. Participants completed a series of questionnaires assessing DT, MT, and PA. Machiavellianism, narcissism, and psychopathy were all significantly associated with higher MT scores (rs =0.45, 0.50, and 0.20, respectively). DT traits and MT were associated with more vigorous PA. Compared to men, women participants had lower scores for DT traits (overall score and psychopathy), while no differences were found for MT or PA in both sexes. DT traits, high MT, and vigorous PA are interrelated. This pattern of results might explain why, for instance, successful professional athletes can at the same time be tough and ruthless.

The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import.

PubMed Central

Schneider, H C; Westermann, B; Neupert, W; Brunner, M

1996-01-01

Import of preproteins into the mitochondrial matrix is driven by the ATP-dependent interaction of mt-Hsp70 with the peripheral inner membrane import protein Tim44 and the preprotein in transit. We show that Mge1p, a co-chaperone of mt-Hsp70, plays a key role in the ATP-dependent import reaction cycle in yeast. Our data suggest a cycle in which the mt-Hsp70-Tim44 complex forms with ATP: Mge1p promotes assembly of the complex in the presence of ATP. Hydrolysis of ATP by mt-Hsp70 occurs in complex with Tim44. Mge1p is then required for the dissociation of the ADP form of mt-Hsp70 from Tim44 after release of inorganic phosphate but before release of ADP. ATP hydrolysis and complex dissociation are accompanied by tight binding of mt-Hsp70 to the preprotein in transit. Subsequently, the release of mt-Hsp70 from the polypeptide chain is triggered by Mge1p which promotes release of ADP from mt-Hsp70. Rebinding of ATP to mt-Hsp70 completes the reaction cycle. Images PMID:8918457

Decreased Circulating mtDNA Levels in Professional Male Volleyball Players.

PubMed

Nasi, Milena; Cristani, Alessandro; Pinti, Marcello; Lamberti, Igor; Gibellini, Lara; De Biasi, Sara; Guazzaloca, Alessandro; Trenti, Tommaso; Cossarizza, Andrea

2016-01-01

Exercise exerts various effects on the immune system, and evidence is emerging on its anti-inflammatory effects; the mechanisms on the basis of these modifications are poorly understood. Mitochondrial DNA (mtDNA) released from damaged cells acts as a molecule containing the so-called damage-associated molecular patterns and can trigger sterile inflammation. Indeed, high plasma levels of mtDNA are associated to several inflammatory conditions and physiological aging and longevity. The authors evaluated plasma mtDNA in professional male volleyball players during seasonal training and the possible correlation between mtDNA levels and clinical parameters, body composition, and physical performance. Plasma mtDNA was quantified by real-time PCR every 2 mo in 12 professional volleyball players (PVPs) during 2 consecutive seasons. As comparison, 20 healthy nonathlete male volunteers (NAs) were analyzed. The authors found lower levels of mtDNA in plasma of PVPs than in NAs. However, PVPs showed a decrease of circulating mtDNA only in the first season, while no appreciable variations were observed during the second season. No correlation was observed among mtDNA, hematochemical, and anthropometric parameters. Regular physical activity appeared associated with lower levels of circulating mtDNA, further confirming the protective, anti-inflammatory effect of exercise.

MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis

PubMed Central

Rebustini, Ivan T.; Myers, Christopher; Lassiter, Keyonica S.; Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn; Pedchenko, Vadim; Hudson, Billy G.; Hoffman, Matthew P.

2009-01-01

Summary Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Importantly, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA-treatment, increasing MT-MMP and pro-proliferative gene expression via β1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA-treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis. PMID:19853562

Recombination-dependent mtDNA partitioning: in vivo role of Mhr1p to promote pairing of homologous DNA.

PubMed

Ling, Feng; Shibata, Takehiko

2002-09-02

Yeast mhr1-1 was isolated as a defective mutation in mitochondrial DNA (mtDNA) recombination. About half of mhr1-1 cells lose mtDNA during growth at a higher temperature. Here, we show that mhr1-1 exhibits a defect in the partitioning of nascent mtDNA into buds and is a base-substitution mutation in MHR1 encoding a mitochondrial matrix protein. We found that the Mhr1 protein (Mhr1p) has activity to pair single-stranded DNA and homologous double-stranded DNA to form heteroduplex joints in vitro, and that mhr1-1 causes the loss of this activity, indicating its role in homologous mtDNA recombination. While the majority of the mtDNA in the mother cells consists of head-to-tail concatemers, more than half of the mtDNA in the buds exists as genome-sized monomers. The mhr1-1 deltacce1 double mutant cells do not maintain any mtDNA, indicating the strict dependence of mtDNA maintenance on recombination functions. These results suggest a mechanism for mtDNA inheritance similar to that operating in the replication and packaging of phage DNA.

Estimates of Continental Ancestry Vary Widely among Individuals with the Same mtDNA Haplogroup

PubMed Central

Emery, Leslie S.; Magnaye, Kevin M.; Bigham, Abigail W.; Akey, Joshua M.; Bamshad, Michael J.

2015-01-01

The association between a geographical region and an mtDNA haplogroup(s) has provided the basis for using mtDNA haplogroups to infer an individual’s place of origin and genetic ancestry. Although it is well known that ancestry inferences using mtDNA haplogroups and those using genome-wide markers are frequently discrepant, little empirical information exists on the magnitude and scope of such discrepancies between multiple mtDNA haplogroups and worldwide populations. We compared genetic-ancestry inferences made by mtDNA-haplogroup membership to those made by autosomal SNPs in ∼940 samples of the Human Genome Diversity Panel and recently admixed populations from the 1000 Genomes Project. Continental-ancestry proportions often varied widely among individuals sharing the same mtDNA haplogroup. For only half of mtDNA haplogroups did the highest average continental-ancestry proportion match the highest continental-ancestry proportion of a majority of individuals with that haplogroup. Prediction of an individual’s mtDNA haplogroup from his or her continental-ancestry proportions was often incorrect. Collectively, these results indicate that for most individuals in the worldwide populations sampled, mtDNA-haplogroup membership provides limited information about either continental ancestry or continental region of origin. PMID:25620206

Fission yeast Alp14 is a dose-dependent plus end–tracking microtubule polymerase

PubMed Central

Al-Bassam, Jawdat; Kim, Hwajin; Flor-Parra, Ignacio; Lal, Neeraj; Velji, Hamida; Chang, Fred

2012-01-01

XMAP215/Dis1 proteins are conserved tubulin-binding TOG-domain proteins that regulate microtubule (MT) plus-end dynamics. Here we show that Alp14, a XMAP215 orthologue in fission yeast, Schizosaccharomyces pombe, has properties of a MT polymerase. In vivo, Alp14 localizes to growing MT plus ends in a manner independent of Mal3 (EB1). alp14-null mutants display short interphase MTs with twofold slower assembly rate and frequent pauses. Alp14 is a homodimer that binds a single tubulin dimer. In vitro, purified Alp14 molecules track growing MT plus ends and accelerate MT assembly threefold. TOG-domain mutants demonstrate that tubulin binding is critical for function and plus end localization. Overexpression of Alp14 or only its TOG domains causes complete MT loss in vivo, and high Alp14 concentration inhibits MT assembly in vitro. These inhibitory effects may arise from Alp14 sequestration of tubulin and effects on the MT. Our studies suggest that Alp14 regulates the polymerization state of tubulin by cycling between a tubulin dimer–bound cytoplasmic state and a MT polymerase state that promotes rapid MT assembly. PMID:22696680

Stimulation of microtubule-based transport by nucleation of microtubules on pigment granules

PubMed Central

Semenova, Irina; Gupta, Dipika; Usui, Takeo; Hayakawa, Ichiro; Cowan, Ann; Rodionov, Vladimir

2017-01-01

Microtubule (MT)-based transport can be regulated through changes in organization of MT transport tracks, but the mechanisms that regulate these changes are poorly understood. In Xenopus melanophores, aggregation of pigment granules in the cell center involves their capture by the tips of MTs growing toward the cell periphery, and granule aggregation signals facilitate capture by increasing the number of growing MT tips. This increase could be explained by stimulation of MT nucleation either on the centrosome or on the aggregate of pigment granules that gradually forms in the cell center. We blocked movement of pigment granules to the cell center and compared the MT-nucleation activity of the centrosome in the same cells in two signaling states. We found that granule aggregation signals did not stimulate MT nucleation on the centrosome but did increase MT nucleation activity of pigment granules. Elevation of MT-nucleation activity correlated with the recruitment to pigment granules of a major component of MT-nucleation templates, γ-tubulin, and was suppressed by γ-tubulin inhibitors. We conclude that generation of new MT transport tracks by concentration of the leading pigment granules provides a positive feedback loop that enhances delivery of trailing granules to the cell center. PMID:28381426

Day-night and reproductive cycle profiles of melatonin receptor, kiss, and gnrh expression in orange-spotted grouper (Epinephelus coioides).

PubMed

Chai, Ke; Liu, Xiaochun; Zhang, Yong; Lin, Haoran

2013-07-01

It is suggested that the MT1 melatonin receptor mediates the effects of melatonin on reproduction in rodents. Three melatonin receptor types, MT1, MT2, and Mel1c, have been identified in fish. To understand the potential roles of each type of melatonin receptor on reproduction, we explored the day-night and reproductive cycle profiles of melatonin receptor, kiss, and gnrh expression in the orange-spotted grouper (Epinephelus coioides). cDNAs encoding melatonin receptors (MT1, MT2, and Mel1c) were first isolated from the brain of the orange-spotted grouper. Quantitative real-time PCR analysis demonstrated that the expression levels of MT1 and MT2 were higher in most of the brain areas and pituitary, while mel1c mRNA was mainly distributed in some peripheral tissues and the pituitary. The expression levels of MT1 were much higher than those of MT2 and mel1c in most of the brain regions, and the day-night expression variations of MT1 were counter to those of kiss2 and gnrh1. Reproductive cycle variations in MT1 daytime expression were different from those for kiss2 and gnrh1, and contrary to ovarian fecundity. Our results suggest that MT1 may modulate gnrh1 expression through kiss2, or may directly influence it. Together, these signal cascades may regulate the seasonal breeding of the orange-spotted grouper. As the day-length variations were consistent with the ovarian fecundity variation observed during the reproductive cycle, we infer that photoperiod affects ovarian development of the orange-spotted grouper through MT1. Copyright © 2013 Wiley Periodicals, Inc.

Solubility and stability of melatonin in propylene glycol and 2-hydroxypropyl-beta-cyclodextrin vehicles.

PubMed

Lee, B J; Choi, H G; Kim, C K; Parrott, K A; Ayres, J W; Sack, R L

1997-12-01

The physicochemical properties of melatonin (MT) in propylene glycol (PG) and 2-hydroxypropyl-beta-cyclodextrin (2-HPbetaCD) vehicles were characterized. MT was endothermally decomposed as determined by differential scanning calorimetry (DSC). Melting point and heat of fusion obtained were 116.9+/-0.24 degrees C and 7249+/-217 cal/mol, respectively. MT as received from a manufacture was very pure, at least 99.9%. The solubility of MT in PG solution increased slowly until reaching 40% PG and then steeply increased. Solubility of MT increased linearly as concentration of 2-HPbetaCD without PG increased (R(2)=0.993). MT solubility in the mixtures of PG and 2-HPbetaCD also increased linearly but was less than the sum of its solubility in 2-HPbetaCD and PG individually. The MT solubility was low in water, simulated gastric or intestinal fluid but the highest in the mixture of PG (40 v/v%) and 2-HPbetaCD (30 w/v%) although efficiency of MT solubilization in 2-HPbetaCD decreased as the concentration of PG increased. MT was degraded in a fashion of the first order kinetics (r(2)>0.90). MT was unstable in strong acidic solution (HCl-NaCl buffer, pH 1.4) but relatively stable in other pH values of 4 approximately 10 at 70 degrees C. In HCl-NaCl buffer, MT in 10% PG was more quickly degraded and then slowed down at a higher concentration. However, the degradation rate constant of MT in 2-HPbetaCD was not changed significantly when compared to the water. The current studies can be applied to the dosage formulations for the purpose of enhancing percutaneous absorption or bioavailability of MT.

Metabolic rescue in pluripotent cells from patients with mtDNA disease.

PubMed

Ma, Hong; Folmes, Clifford D L; Wu, Jun; Morey, Robert; Mora-Castilla, Sergio; Ocampo, Alejandro; Ma, Li; Poulton, Joanna; Wang, Xinjian; Ahmed, Riffat; Kang, Eunju; Lee, Yeonmi; Hayama, Tomonari; Li, Ying; Van Dyken, Crystal; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Koski, Amy; Mitalipov, Nargiz; Amato, Paula; Wolf, Don P; Huang, Taosheng; Terzic, Andre; Laurent, Louise C; Izpisua Belmonte, Juan Carlos; Mitalipov, Shoukhrat

2015-08-13

Mitochondria have a major role in energy production via oxidative phosphorylation, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell). Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A>G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS), and 8993T>G and 13513G>A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T>G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.

Effect of mirror therapy combined with somatosensory stimulation on motor recovery and daily function in stroke patients: A pilot study.

PubMed

Lin, Keh-Chung; Chen, Yu-Ting; Huang, Pai-Chuan; Wu, Ching-Yi; Huang, Wen-Ling; Yang, Hsiu-Wen; Lai, Hui-Tsz; Lu, Hung-Ju

2014-07-01

Mirror therapy (MT) has been recommended as a simple, inexpensive approach to treat motor dysfunction. The use of a mesh glove (MG) was suggested to normalize muscle tone that ameliorates motor impairment. Combining two efficient treatment protocols might maximize the benefits from training. This study investigated the effects of MT combined with MG (MG + MT) versus MT alone on motor performance and daily function after stroke. Sixteen patients with chronic unilateral stroke were recruited. A randomized two-group pretest and posttest design was used to randomly assign participants to MG + MT or MT groups. MT involves repetitive bimanual, symmetrical movement practice in which the individual moves the affected limb as much as she/he could while watching the reflective illusion of the unaffected limb's movements from a mirror. The MG + MT group wore a MG on the affected hand during the MT. The Modified Ashworth scale of muscle spasticity (MAS), Action Research Arm Test (ARAT), Box and Block Test (BBT), and Functional Independence Measure (FIM) were administered to evaluate spasticity, and motor and daily function. The results for the BBT (p = 0.013), total scores (p = 0.031), grasping subscales (p = 0.036) of ARAT, and FIM transfer scores (p = 0.013) presented significantly large effects in favor of the MG + MT group. Combining MG with MT significantly improves manual dexterity, grasping, and transfer performance. Adding the MG component into the MT likely increased the richness of sensory input and improved the movement performance more than MT alone. Copyright © 2012. Published by Elsevier B.V.

The XMAP215 Ortholog Alp14 Promotes Microtubule Nucleation in Fission Yeast.

PubMed

Flor-Parra, Ignacio; Iglesias-Romero, Ana Belén; Chang, Fred

2018-06-04

The organization and number of microtubules (MTs) in a cell depend on the proper regulation of MT nucleation. Currently, the mechanism of nucleation is the most poorly understood aspect of MT dynamics. XMAP215/chTOG/Alp14/Stu2 proteins are MT polymerases that stimulate MT polymerization at MT plus ends by binding and releasing tubulin dimers. Although these proteins also localize to MT organizing centers and have nucleating activity in vitro, it is not yet clear whether these proteins participate in MT nucleation in vivo. Here, we demonstrate that in the fission yeast Schizosaccharomyces pombe, the XMAP215 ortholog Alp14 is critical for efficient MT nucleation in vivo. In multiple assays, loss of Alp14 function led to reduced nucleation rate and numbers of interphase MT bundles. Conversely, activation of Alp14 led to increased nucleation frequency. Alp14 associated with Mto1 and γ-tubulin complex components, and artificially targeting Alp14 to the γ-tubulin ring complexes (γ-TuRCs) stimulated nucleation. In imaging individual nucleation events, we found that Alp14 transiently associated with a γ-tubulin particle shortly before the appearance of a new MT. The transforming acidic coiled-coil (TACC) ortholog Alp7 mediated the localization of Alp14 at nucleation sites but not plus ends, and was required for efficient nucleation but not for MT polymerization. Our findings provide the strongest evidence to date that Alp14 serves as a critical MT nucleation factor in vivo. We suggest a model in which Alp14 associates with the γ-tubulin complex in an Alp7-dependent manner to facilitate the assembly or stabilization of the nascent MT. Copyright © 2018 Elsevier Ltd. All rights reserved.

Melatonin regulates somatotrope and lactotrope function through common and distinct signaling pathways in cultured primary pituitary cells from female primates.

PubMed

Ibáñez-Costa, Alejandro; Córdoba-Chacón, José; Gahete, Manuel D; Kineman, Rhonda D; Castaño, Justo P; Luque, Raúl M

2015-03-01

Melatonin (MT) is secreted by the pineal gland and exhibits a striking circadian rhythm in its release. Depending on the species studied, some pituitary hormones also display marked circadian/seasonal patterns and rhythms of secretion. However, the precise relationship between MT and pituitary function remains controversial, and studies focusing on the direct role of MT in normal pituitary cells are limited to nonprimate species. Here, adult normal primate (baboons) primary pituitary cell cultures were used to determine the direct impact of MT on the functioning of all pituitary cell types from the pars distalis. MT increased GH and prolactin (PRL) expression/release in a dose- and time-dependent fashion, a response that was blocked by somatostatin. However, MT did not significantly affect ACTH, FSH, LH, or TSH expression/release. MT did not alter GHRH- or ghrelin-induced GH and/or PRL secretions, suggesting that MT may activate similar signaling pathways as ghrelin/GHRH. The effects of MT on GH/PRL release, which are likely mediated through MT1 receptor, involve both common (adenylyl cyclase/protein kinase A/extracellular calcium-channels) and distinct (phospholipase C/intracellular calcium-channels) signaling pathways. Actions of MT on pituitary cells also included regulation of the expression of other key components for the control of somatotrope/lactotrope function (GHRH, ghrelin, and somatostatin receptors). These results show, for the first time in a primate model, that MT directly regulates somatotrope/lactotrope function, thereby lending support to the notion that the actions of MT on these cells might substantially contribute to the define daily patterns of GH and PRL observed in primates and perhaps in humans.

Tissue- and cell-specific expression of metallothionein genes in cadmium- and copper-exposed mussels analyzed by in situ hybridization and RT-PCR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zorita, I.; Bilbao, E.; Schad, A.

2007-04-15

Metallothioneins (MTs) are metal-inducible proteins that can be used as biomarkers of metal exposure. In mussels two families of MT isoforms (MT10 and MT20) have been characterized. In this study, mussels (Mytilus galloprovincialis) were exposed to 200 ppb Cd and 40 ppb Cu for 2 and 9 days to characterize the tissue and isoform specificity of metal-induced MT expression. Non-radioactive in situ hybridization demonstrated that both MT isoforms were mainly transcribed in digestive tubule epithelial cells, especially in basophilic cells. Weaker MT expression was detected in non-ciliated duct cells, stomach and gill epithelial cells, haemocytes, adipogranular cells, spermatic follicles andmore » oocytes. RT-PCR resulted in cloning of a novel M. galloprovincialis isoform homologous to recently cloned Mytilus edulis intron-less MT10B isoform. In gills, Cd only affected MT10 gene expression after 2 days of exposure while increases in MT protein levels occurred at day 9. In the digestive gland, a marked increase of both isoforms, but especially of MT20, was accompanied by increased levels of MT proteins and basophilic cell volume density (Vv{sub BAS}) after 2 and 9 days and of intralysosomal metal accumulation in digestive cells after 9 days. Conversely, although metal was accumulated in digestive cells lysosomes and the Vv{sub BAS} increased in Cu-exposed mussels, Cu exposure did not produce an increase of MT gene expression or MT protein levels. These data suggest that MTs are expressed in a tissue-, cell- and isoform-specific way in response to different metals.« less

Mt, St. Helens, Mt. Adams, and Mt. Rainier, WA, USA

NASA Technical Reports Server (NTRS)

1992-01-01

This view of Mt. St. Helens (46.5N, 122.0W), taken 12 years after the volcanic eruption on 18 May 1980, in which the top 1300 ft. of the 9,677 ft. mountain was blown away, shows the rapid vegetation recovery within the blast area. Many fir trees have grown to heights of 20 ft. within the 150 square mile devastated area. Mt. Adams, an extinct volcano is just to the west and Mt. Rainier is to the north. Checkerboard logging can be seen throughout.

Segregation and manifestations of the mtDNA tRNA[sup Lys] A[r arrow]G[sup (8344)] mutation of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larsson, N.G.; Tulinius, M.H.; Holme, E.

1992-12-01

The authors have studied the segregation and manifestations of the tRNA[sup Lys] A[r arrow]G[sup (8344)] mutation of mtDNA. Three unrelated patients with myoclonus epilepsy and ragged-red fibers (MERRF) syndrome were investigated, along with 30 of their maternal relatives. Mutated mtDNA was not always found in the offspring of women carrying the tRNA[sup Lys] mutation. Four women had 10%-33% of mutated mtDNA in lymphocytes, and no mutated mtDNA was found in 7 of their 14 investigated children. The presence of mutated mtDNA was excluded at a level of 3:1,000. Five women had a proportion of 43%-73% mutated mtDNA in lymphocytes, andmore » mutated mtDNA was found in all their 12 investigated children. This suggests that the risk for transmission of mutated mtDNA to the offspring increases if high levels are present in the mother and that, above a threshold level of 35%-40%, it is very likely that transmission will occur to all children. The three patients with MERRF syndrone had, in muscle, both 94%-96% mutated mtDNA and biochemical and histochemical evidence of a respiratory-chain dysfunction. Four relatives had a proportion of 61%-92% mutated mtDNA in muscle, and biochemical measurements showed a normal respiratory-chain function in muscle in all cases. These findings suggest that >92% of mtDNA with the tRNA[sup Lys] mutation in muscle is required to cause a respiratory-chain dysfunction that can be detected by biochemical methods. There was a positive correlation between the levels of mtDNA with the tRNA[sup Lys] mutation in lymphocytes and the levels in muscle, in all nine investigated cases. The levels of mutated mtDNA were higher in muscle than in lymphocytes in all cases. 30 refs., 3 figs., 5 tabs.« less

Metallothionein expression is suppressed in primary human hepatocellular carcinomas and is mediated through inactivation of CCAAT/enhancer binding protein alpha by phosphatidylinositol 3-kinase signaling cascade.

PubMed

Datta, Jharna; Majumder, Sarmila; Kutay, Huban; Motiwala, Tasneem; Frankel, Wendy; Costa, Robert; Cha, Hyuk C; MacDougald, Ormond A; Jacob, Samson T; Ghoshal, Kalpana

2007-03-15

Reactive oxygen species (ROS) resulting from chronic inflammation cause liver injury leading to transformation of regenerating hepatocytes. Metallothioneins (MT), induced at high levels by oxidative stress, are potent scavengers of ROS. Here, we report that the levels of MT-1 and MT-2A are drastically reduced in primary human hepatocellular carcinomas (HCCs) and in diethylnitrosamine-induced liver tumors in mice, which is primarily due to transcriptional repression. Expression of the transcription factor, MTF-1, essential for MT expression, and its target gene Zn-T1 that encodes the zinc transporter-1 was not significantly altered in HCCs. Inhibitors of both phosphatidylinositol 3-kinase (PI3K) and its downstream target AKT increased expression of MT genes in HCC cells but not in liver epithelial cells. Suppression of MT-1 and MT-2A by ectopic expression of the constitutively active PI3K or AKT and their up-regulation by dominant-negative PI3K or AKT mutant confirmed negative regulation of MT expression by PI3K/AKT signaling pathway. Further, treatment of cells with a specific inhibitor of glycogen synthase kinase-3 (GSK-3), a downstream effector of PI3K/AKT, inhibited MT expression specifically in HCC cells. Short interfering RNA-mediated depletion of CCAAT/enhancer binding protein alpha (C/EBPalpha), a target of GSK-3, impeded MT expression, which could not be reversed by PI3K inhibitors. DNA binding activity of C/EBPalpha and its phosphorylation at T222 and T226 by GSK-3 are required for MT expression. MTF-1 and C/EBPalpha act in concert to increase MT-2A expression, which probably explains the high level of MT expression in the liver. This study shows the role of PI3K/AKT signaling pathway and C/EBPalpha in regulation of MT expression in hepatocarcinogenesis.

Identification of proteins associated with the yeast mitochondrial RNA polymerase by tandem affinity purification

PubMed Central

Markov, Dmitriy A; Savkina, Maria; Anikin, Michael; Del Campo, Mark; Ecker, Karen; Lambowitz, Alan M; De Gnore, Jon P; McAllister, William T

2009-01-01

The abundance of mitochondrial (mt) transcripts varies under different conditions, and is thought to depend upon rates of transcription initiation, transcription termination/attenuation and RNA processing/degradation. The requirement to maintain the balance between RNA synthesis and processing may involve coordination between these processes; however, little is known about factors that regulate the activity of mtRNA polymerase (mtRNAP). Recent attempts to identify mtRNAP–protein interactions in yeast by means of a generalized tandem affinity purification (TAP) protocol were not successful, most likely because they involved a C-terminal mtRNAP–TAP fusion (which is incompatible with mtRNAP function) and because of the use of whole-cell solubilization protocols that did not preserve the integrity of mt protein complexes. Based upon the structure of T7 RNAP (to which mtRNAPs show high sequence similarity), we identified positions in yeast mtRNAP that allow insertion of a small affinity tag, confirmed the mature N-terminus, constructed a functional N-terminal TAP–mtRNAP fusion, pulled down associated proteins, and identified them by LC–MS–MS. Among the proteins found in the pull-down were a DEAD-box protein (Mss116p) and an RNA-binding protein (Pet127p). Previous genetic experiments suggested a role for these proteins in linking transcription and RNA degradation, in that a defect in the mt degradadosome could be suppressed by overexpression of either of these proteins or, independently, by mutations in either mtRNAP or its initiation factor Mtf1p. Further, we found that Mss116p inhibits transcription by mtRNAP in vitro in a steady-state reaction. Our results support the hypothesis that Mss116p and Pet127p are involved in modulation of mtRNAP activity. Copyright © 2009 John Wiley & Sons, Ltd. PMID:19536766

Melatonin administration alters nicotine preference consumption via signaling through high-affinity melatonin receptors.

PubMed

Horton, William J; Gissel, Hannah J; Saboy, Jennifer E; Wright, Kenneth P; Stitzel, Jerry A

2015-07-01

While it is known that tobacco use varies across the 24-h day, the time-of-day effects are poorly understood. Findings from several previous studies indicate a potential role for melatonin in these time-of-day effects; however, the specific underlying mechanisms have not been well characterized. Understanding of these mechanisms may lead to potential novel smoking cessation treatments. The objective of this study is examine the role of melatonin and melatonin receptors in nicotine free-choice consumption A two-bottle oral nicotine choice paradigm was utilized with melatonin supplementation in melatonin-deficient mice (C57BL/6J) or without melatonin supplementation in mice proficient at melatonin synthesis (C3H/Ibg) compared to melatonin-proficient mice lacking both or one of the high-affinity melatonin receptors (MT1 and MT2; double-null mutant DM, or MT1 or MT2). Preference for bitter and sweet tastants also was assessed in wild-type and MT1 and MT2 DM mice. Finally, home cage locomotor monitoring was performed to determine the effect of melatonin administration on activity patterns. Supplemental melatonin in drinking water significantly reduced free-choice nicotine consumption in C57BL/6J mice, which do not produce endogenous melatonin, while not altering activity patterns. Independently, genetic deletion of both MT1 and MT2 receptors in a melatonin-proficient mouse strain (C3H) resulted in significantly more nicotine consumption than controls. However, single genetic deletion of either the MT1 or MT2 receptor alone did not result in increased nicotine consumption. Deletion of MT1 and MT2 did not impact taste preference. This study demonstrates that nicotine consumption can be affected by exogenous or endogenous melatonin and requires at least one of the high-affinity melatonin receptors. The fact that expression of either the MT1 or MT2 melatonin receptor is sufficient to maintain lower nicotine consumption suggests functional overlap and potential mechanistic explanations.

Acetic acid and aromatics units planned in China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alperowicz, N.

1993-01-27

The Shanghai Wujing Chemical Complex (SWCC; Shanghai) is proceeding with construction of an acetic acid plant. The 100,000-m.t./year until will use BP Chemicals carbonylation technology, originally developed by Monsanto. John Brown has been selected by China National Technical Import Corp. (CNTIC) to supply the plant, Chinese sources say. The UK contractor, which competed against Mitsui Engineering Shipbuilding (Tokyo) and Lurgi (Frankfurt), has built a similar plant for BP in the UK, although using different technology. The new plant will require 54,000 m.t./year of methanol, which is available onsite. Carbon monoxide will be delivered from a new plant. The acetic acidmore » unit will joint two other acetic plants in China supplied some time ago by Uhde (Dortmund). SWCC is due to be integrated with two adjacent complexes to form Shanghai Pacific Chemical. Meanwhile, four groups are competing to supply a UOP-process aromatics complex for Jilin Chemical Industrial Corp. They are Toyo Engineering, Lurgi, Lucky/Foster Wheeler, and Eurotechnica. The complex will include plants with annual capacities for 115,000 m.t. of benzene, 90,000 m.t. of ortho-xylene, 93,000 m.t. of mixed xylenes, and 20,000 m.t. of toluene. The plants will form part of a $2-billion petrochemical complex based on a 300,000-m.t./year ethylene plant awarded last year to a consortium of Samsung Engineering and Linde. Downstream plants will have annual capacities for 120,000 m.t. of linear low-density polyethylene, 80,000 m.t. of ethylene oxide, 100,000 m.t. of ethylene glycol, 80,000 m.t. of phenol, 100,000 m.t. of acrylonitrile, 20,000 m.t. of sodium cyanide, 40,000 m.t. of phthalic anhydride, 40,000 m.t. of ethylene propylene rubber, 20,000 m.t. of styrene butadiene styrene, and 30,000 m.t. of acrylic fiber.« less

Epoxyalkane:Coenzyme M Transferase Gene Diversity and Distribution in Groundwater Samples from Chlorinated-Ethene-Contaminated Sites

PubMed Central

Liu, Xikun

2016-01-01

ABSTRACT Epoxyalkane:coenzyme M transferase (EaCoMT) plays a critical role in the aerobic biodegradation and assimilation of alkenes, including ethene, propene, and the toxic chloroethene vinyl chloride (VC). To improve our understanding of the diversity and distribution of EaCoMT genes in the environment, novel EaCoMT-specific terminal-restriction fragment length polymorphism (T-RFLP) and nested-PCR methods were developed and applied to groundwater samples from six different contaminated sites. T-RFLP analysis revealed 192 different EaCoMT T-RFs. Using clone libraries, we retrieved 139 EaCoMT gene sequences from these samples. Phylogenetic analysis revealed that a majority of the sequences (78.4%) grouped with EaCoMT genes found in VC- and ethene-assimilating Mycobacterium strains and Nocardioides sp. strain JS614. The four most-abundant T-RFs were also matched with EaCoMT clone sequences related to Mycobacterium and Nocardioides strains. The remaining EaCoMT sequences clustered within two emergent EaCoMT gene subgroups represented by sequences found in propene-assimilating Gordonia rubripertincta strain B-276 and Xanthobacter autotrophicus strain Py2. EaCoMT gene abundance was positively correlated with VC and ethene concentrations at the sites studied. IMPORTANCE The EaCoMT gene plays a critical role in assimilation of short-chain alkenes, such as ethene, VC, and propene. An improved understanding of EaCoMT gene diversity and distribution is significant to the field of bioremediation in several ways. The expansion of the EaCoMT gene database and identification of incorrectly annotated EaCoMT genes currently in the database will facilitate improved design of environmental molecular diagnostic tools and high-throughput sequencing approaches for future bioremediation studies. Our results further suggest that potentially significant aerobic VC degraders in the environment are not well represented in pure culture. Future research should aim to isolate and characterize aerobic VC-degrading bacteria from these underrepresented groups. PMID:27016563

Development of forensic-quality full mtGenome haplotypes: success rates with low template specimens.

PubMed

Just, Rebecca S; Scheible, Melissa K; Fast, Spence A; Sturk-Andreaggi, Kimberly; Higginbotham, Jennifer L; Lyons, Elizabeth A; Bush, Jocelyn M; Peck, Michelle A; Ring, Joseph D; Diegoli, Toni M; Röck, Alexander W; Huber, Gabriela E; Nagl, Simone; Strobl, Christina; Zimmermann, Bettina; Parson, Walther; Irwin, Jodi A

2014-05-01

Forensic mitochondrial DNA (mtDNA) testing requires appropriate, high quality reference population data for estimating the rarity of questioned haplotypes and, in turn, the strength of the mtDNA evidence. Available reference databases (SWGDAM, EMPOP) currently include information from the mtDNA control region; however, novel methods that quickly and easily recover mtDNA coding region data are becoming increasingly available. Though these assays promise to both facilitate the acquisition of mitochondrial genome (mtGenome) data and maximize the general utility of mtDNA testing in forensics, the appropriate reference data and database tools required for their routine application in forensic casework are lacking. To address this deficiency, we have undertaken an effort to: (1) increase the large-scale availability of high-quality entire mtGenome reference population data, and (2) improve the information technology infrastructure required to access/search mtGenome data and employ them in forensic casework. Here, we describe the application of a data generation and analysis workflow to the development of more than 400 complete, forensic-quality mtGenomes from low DNA quantity blood serum specimens as part of a U.S. National Institute of Justice funded reference population databasing initiative. We discuss the minor modifications made to a published mtGenome Sanger sequencing protocol to maintain a high rate of throughput while minimizing manual reprocessing with these low template samples. The successful use of this semi-automated strategy on forensic-like samples provides practical insight into the feasibility of producing complete mtGenome data in a routine casework environment, and demonstrates that large (>2kb) mtDNA fragments can regularly be recovered from high quality but very low DNA quantity specimens. Further, the detailed empirical data we provide on the amplification success rates across a range of DNA input quantities will be useful moving forward as PCR-based strategies for mtDNA enrichment are considered for targeted next-generation sequencing workflows. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Additional mitochondrial DNA influences the interactions between the nuclear and mitochondrial genomes in a bovine embryo model of nuclear transfer.

PubMed

Srirattana, Kanokwan; St John, Justin C

2018-05-08

We generated cattle embryos using mitochondrial supplementation and somatic cell nuclear transfer (SCNT), named miNT, to determine how additional mitochondrial DNA (mtDNA) modulates the nuclear genome. To eliminate any confounding effects from somatic cell mtDNA in intraspecies SCNT, donor cell mtDNA was depleted prior to embryo production. Additional oocyte mtDNA did not affect embryo development rates but increased mtDNA copy number in blastocyst stage embryos. Moreover, miNT-derived blastocysts had different gene expression profiles when compared with SCNT-derived blastocysts. Additional mtDNA increased expression levels of genes involved in oxidative phosphorylation, cell cycle and DNA repair. Supplementing the embryo culture media with a histone deacetylase inhibitor, Trichostatin A (TSA), had no beneficial effects on the development of miNT-derived embryos, unlike SCNT-derived embryos. When compared with SCNT-derived blastocysts cultured in the presence of TSA, additional mtDNA alone had beneficial effects as the activity of glycolysis may increase and embryonic cell death may decrease. However, these beneficial effects were not found with additional mtDNA and TSA together, suggesting that additional mtDNA alone enhances reprogramming. In conclusion, additional mtDNA increased mtDNA copy number and expression levels of genes involved in energy production and embryo development in blastocyst stage embryos emphasising the importance of nuclear-mitochondrial interactions.

Paternal leakage of mitochondrial DNA in experimental crosses of populations of the potato cyst nematode Globodera pallida.

PubMed

Hoolahan, Angelique H; Blok, Vivian C; Gibson, Tracey; Dowton, Mark

2011-12-01

Animal mtDNA is typically assumed to be maternally inherited. Paternal mtDNA has been shown to be excluded from entering the egg or eliminated post-fertilization in several animals. However, in the contact zones of hybridizing species and populations, the reproductive barriers between hybridizing organisms may not be as efficient at preventing paternal mtDNA inheritance, resulting in paternal leakage. We assessed paternal mtDNA leakage in experimental crosses of populations of a cyst-forming nematode, Globodera pallida. A UK population, Lindley, was crossed with two South American populations, P5A and P4A. Hybridization of these populations was supported by evidence of nuclear DNA from both the maternal and paternal populations in the progeny. To assess paternal mtDNA leakage, a ~3.4 kb non-coding mtDNA region was analyzed in the parental populations and in the progeny. Paternal mtDNA was evident in the progeny of both crosses involving populations P5A and P4A. Further, paternal mtDNA replaced the maternal mtDNA in 22 and 40 % of the hybrid cysts from these crosses, respectively. These results indicate that under appropriate conditions, paternal leakage occurs in the mtDNA of parasitic nematodes, and supports the hypothesis that hybrid zones facilitate paternal leakage. Thus, assumptions of strictly maternal mtDNA inheritance may be frequently violated, particularly when divergent populations interbreed.

Immobilization of metallothionein to carbon paste electrode surface via anti-MT antibodies and its use for biosensing of silver.

PubMed

Trnkova, Libuse; Krizkova, Sona; Adam, Vojtech; Hubalek, Jaromir; Kizek, Rene

2011-01-15

In this paper, heavy metal biosensor based on immobilization of metallothionein (MT) to the surface of carbon paste electrode (CPE) via anti-MT-antibodies is reported. First, the evaluation of MT electroactivity was done. The attention was focused on the capturing of MT to the CPE surface. Antibodies incorporated and mixed into carbon paste were stable; even after two weeks the observed changes in signal height were lower than 5%. Further, the interaction of MT with polyclonal chicken antibodies incorporated in carbon paste electrode was determined by square-wave voltammetry. In the voltammogram, two signals--labelled as cys(MT) and W(a)--were observed. The cys(MT) corresponded to -SH moieties of MT and W(a) corresponded to tryptophan residues of chicken antibodies. Time of interaction (300 s) and MT concentration (125 μg/ml) were optimized to suggest a silver(I) ions biosensor. Biosensor (CPE modified with anti-MT antibody) prepared under the optimized conditions was then used for silver(I) ions detection. The detection limit (3 S/N) for silver(I) ions was estimated as 0.5 nM. The proposed biosensor was tested by detection spiking of silver(I) ions in various water samples (from very pure distilled water to rainwater). Recoveries varied from 74 to 104%. Copyright © 2010 Elsevier B.V. All rights reserved.

Efficient inhibition of heavy metal release from mine tailings against acid rain exposure by triethylenetetramine intercalated montmorillonite (TETA-Mt).

PubMed

Gong, Beini; Wu, Pingxiao; Huang, Zhujian; Li, Yuanyuan; Yang, Shanshan; Dang, Zhi; Ruan, Bo; Kang, Chunxi

2016-11-15

The potential application of triethylenetetramine intercalated montmorillonite (TETA-Mt) in mine tailings treatment and AMD (acid mine drainage) remediation was investigated with batch experiments. The structural and morphological characteristics of TETA-Mt were analyzed with XRD, FTIR, DTG-TG and SEM. The inhibition efficiencies of TETA-Mt against heavy metal release from mine tailings when exposed to acid rain leaching was examined and compared with that of triethylenetetramine (TETA) and Mt. Results showed that the overall inhibition by TETA-Mt surpassed that by TETA or Mt for various heavy metal ions over an acid rain pH range of 3-5.6 and a temperature range of 25-40°C. When mine tailings were exposed to acid rain of pH 4.8 (the average rain pH of the mining site where the mine tailings were from), TETA-Mt achieved an inhibition efficiency of over 90% for Cu(2+), Zn(2+), Cd(2+) and Mn(2+) release, and 70% for Pb(2+) at 25°C. It was shown that TETA-Mt has a strong buffering capacity. Moreover, TETA-Mt was able to adsorb heavy metal ions and the adsorption process was fast, suggesting that coordination was mainly responsible. These results showed the potential of TETA-Mt in AMD mitigation, especially in acid rain affected mining area. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular Insights into the Potential Toxicological Interaction of 2-Mercaptothiazoline with the Antioxidant Enzyme—Catalase

PubMed Central

Huang, Zhenxing; Huang, Ming; Mi, Chenyu; Wang, Tao; Chen, Dong; Teng, Yue

2016-01-01

2-mercaptothiazoline (2-MT) is widely used in many industrial fields, but its residue is potentially harmful to the environment. In this study, to evaluate the biological toxicity of 2-MT at protein level, the interaction between 2-MT and the pivotal antioxidant enzyme—catalase (CAT) was investigated using multiple spectroscopic techniques and molecular modeling. The results indicated that the CAT fluorescence quenching caused by 2-MT should be dominated by a static quenching mechanism through formation of a 2-MT/CAT complex. Furthermore, the identifications of the binding constant, binding forces, and the number of binding sites demonstrated that 2-MT could spontaneously interact with CAT at one binding site mainly via Van der Waals’ forces and hydrogen bonding. Based on the molecular docking simulation and conformation dynamic characterization, it was found that 2-MT could bind into the junctional region of CAT subdomains and that the binding site was close to enzyme active sites, which induced secondary structural and micro-environmental changes in CAT. The experiments on 2-MT toxicity verified that 2-MT significantly inhibited CAT activity via its molecular interaction, where 2-MT concentration and exposure time both affected the inhibitory action. Therefore, the present investigation provides useful information for understanding the toxicological mechanism of 2-MT at the molecular level. PMID:27537873

Parental Perceptions, Experiences, and Desires of Music Therapy

PubMed Central

Kong, Ha-Kyung; Karahalios, Karrie

2016-01-01

Music therapy (MT) is a therapeutic practice where a therapist uses music to enhance the life quality for their patients. Children have an innate enjoyment of music, making music an effective medium for exploring their potential. In this study, we explore the parental perception of MT through an online survey. Contrary to the public perception that MT only addresses emotional needs, 47 out of 59 parents reported seeing improvements in other areas including behavioral, cognitive, linguistic, and social changes. All but one parent indicated that they would recommend MT to others. The survey results further revealed that even parents of children participating in MT had misconceptions regarding MT, which we describe in the paper. Parents reported inaccessibility and cost as other major limitations surrounding MT adoption. We conclude by discussing how technology solutions could mitigate issues with definition, distance, and cost, while maintaining the benefits of MT. PMID:28269946

Thermodynamics of Pb(ii) and Zn(ii) binding to MT-3, a neurologically important metallothionein.

PubMed

Carpenter, M C; Shami Shah, A; DeSilva, S; Gleaton, A; Su, A; Goundie, B; Croteau, M L; Stevenson, M J; Wilcox, D E; Austin, R N

2016-06-01

Isothermal titration calorimetry (ITC) was used to quantify the thermodynamics of Pb(2+) and Zn(2+) binding to metallothionein-3 (MT-3). Pb(2+) binds to zinc-replete Zn7MT-3 displacing each zinc ion with a similar change in free energy (ΔG) and enthalpy (ΔH). EDTA chelation measurements of Zn7MT-3 and Pb7MT-3 reveal that both metal ions are extracted in a tri-phasic process, indicating that they bind to the protein in three populations with different binding thermodynamics. Metal binding is entropically favoured, with an enthalpic penalty that reflects the enthalpic cost of cysteine deprotonation accompanying thiolate ligation of the metal ions. These data indicate that Pb(2+) binding to both apo MT-3 and Zn7MT-3 is thermodynamically favourable, and implicate MT-3 in neuronal lead biochemistry.

Parental Perceptions, Experiences, and Desires of Music Therapy.

PubMed

Kong, Ha-Kyung; Karahalios, Karrie

2016-01-01

Music therapy (MT) is a therapeutic practice where a therapist uses music to enhance the life quality for their patients. Children have an innate enjoyment of music, making music an effective medium for exploring their potential. In this study, we explore the parental perception of MT through an online survey. Contrary to the public perception that MT only addresses emotional needs, 47 out of 59 parents reported seeing improvements in other areas including behavioral, cognitive, linguistic, and social changes. All but one parent indicated that they would recommend MT to others. The survey results further revealed that even parents of children participating in MT had misconceptions regarding MT, which we describe in the paper. Parents reported inaccessibility and cost as other major limitations surrounding MT adoption. We conclude by discussing how technology solutions could mitigate issues with definition, distance, and cost, while maintaining the benefits of MT.

Fourier transform infrared spectra and molecular structure of 5-methoxytryptamine, N-acetyl-5-methoxytryptamine and N-phenylsulfonamide-5-methoxytryptamine

NASA Astrophysics Data System (ADS)

Bayari, S.; Ide, S.

2003-04-01

5-Methoxytryptamine (5-MT) is a potent antioxidant and has radioprotective action. N-acetyl-5-methoxytryptamine (melatonin, NA-5-MT) is a free radical scavenger and antioxidant, which protects against oxidative damage due to a variety of toxicants. The infrared spectra of 5-MT, NA-5-MT and new synthesized N-phenylsulfonamide-5-methoxytryptamine (PS-5-MT) were investigated in the region between 4000 and 400 cm -1. Vibrational assignments of the molecules have been made for fundamental modes on the basis of the group vibrational concept, infrared intensity and comparison with the assignments for related molecules. X-ray powder diffraction patterns of molecules were also recorded. In order to optimize the geometries of the molecules, molecular mechanic calculations (MM3) were performed. Conformational analysis of 5-MT, NA-5-MT and PS-5-MT was also established by the using PM3 method.

A role for recombination junctions in the segregation of mitochondrial DNA in yeast.

PubMed

Lockshon, D; Zweifel, S G; Freeman-Cook, L L; Lorimer, H E; Brewer, B J; Fangman, W L

1995-06-16

In S. cerevisiae, mitochondrial DNA (mtDNA) molecules, in spite of their high copy number, segregate as if there were a small number of heritable units. The rapid segregation of mitochondrial genomes can be analyzed using mtDNA deletion variants. These small, amplified genomes segregate preferentially from mixed zygotes relative to wild-type mtDNA. This segregation advantage is abolished by mutations in a gene, MGT1, that encodes a recombination junction-resolving enzyme. We show here that resolvase deficiency causes a larger proportion of molecules to be linked together by recombination junctions, resulting in the aggregation of mtDNA into a small number of cytological structures. This change in mtDNA structure can account for the increased mitotic loss of mtDNA and the altered pattern of mtDNA segregation from zygotes. We propose that the level of unresolved recombination junctions influences the number of heritable units of mtDNA.

MT3DMS: Model use, calibration, and validation

USGS Publications Warehouse

Zheng, C.; Hill, Mary C.; Cao, G.; Ma, R.

2012-01-01

MT3DMS is a three-dimensional multi-species solute transport model for solving advection, dispersion, and chemical reactions of contaminants in saturated groundwater flow systems. MT3DMS interfaces directly with the U.S. Geological Survey finite-difference groundwater flow model MODFLOW for the flow solution and supports the hydrologic and discretization features of MODFLOW. MT3DMS contains multiple transport solution techniques in one code, which can often be important, including in model calibration. Since its first release in 1990 as MT3D for single-species mass transport modeling, MT3DMS has been widely used in research projects and practical field applications. This article provides a brief introduction to MT3DMS and presents recommendations about calibration and validation procedures for field applications of MT3DMS. The examples presented suggest the need to consider alternative processes as models are calibrated and suggest opportunities and difficulties associated with using groundwater age in transport model calibration.

Structural insight into TPX2-stimulated microtubule assembly

PubMed Central

2017-01-01

During mitosis and meiosis, microtubule (MT) assembly is locally upregulated by the chromatin-dependent Ran-GTP pathway. One of its key targets is the MT-associated spindle assembly factor TPX2. The molecular mechanism of how TPX2 stimulates MT assembly remains unknown because structural information about the interaction of TPX2 with MTs is lacking. Here, we determine the cryo-electron microscopy structure of a central region of TPX2 bound to the MT surface. TPX2 uses two flexibly linked elements (’ridge’ and ‘wedge’) in a novel interaction mode to simultaneously bind across longitudinal and lateral tubulin interfaces. These MT-interacting elements overlap with the binding site of importins on TPX2. Fluorescence microscopy-based in vitro reconstitution assays reveal that this interaction mode is critical for MT binding and facilitates MT nucleation. Together, our results suggest a molecular mechanism of how the Ran-GTP gradient can regulate TPX2-dependent MT formation. PMID:29120325

Induction of metallothionein in mouse cerebellum and cerebrum with low-dose thimerosal injection.

PubMed

Minami, Takeshi; Miyata, Eriko; Sakamoto, Yamato; Yamazaki, Hideo; Ichida, Seiji

2010-04-01

Thimerosal, an ethyl mercury compound, is used worldwide as a vaccine preservative. We previously observed that the mercury concentration in mouse brains did not increase with the clinical dose of thimerosal injection, but the concentration increased in the brain after the injection of thimerosal with lipopolysaccharide, even if a low dose of thimerosal was administered. Thimerosal may penetrate the brain, but is undetectable when a clinical dose of thimerosal is injected; therefore, the induction of metallothionein (MT) messenger RNA (mRNA) and protein was observed in the cerebellum and cerebrum of mice after thimerosal injection, as MT is an inducible protein. MT-1 mRNA was expressed at 6 and 9 h in both the cerebrum and cerebellum, but MT-1 mRNA expression in the cerebellum was three times higher than that in the cerebrum after the injection of 12 microg/kg thimerosal. MT-2 mRNA was not expressed until 24 h in both organs. MT-3 mRNA was expressed in the cerebellum from 6 to 15 h after the injection, but not in the cerebrum until 24 h. MT-1 and MT-3 mRNAs were expressed in the cerebellum in a dose-dependent manner. Furthermore, MT-1 protein was detected from 6 to 72 h in the cerebellum after 12 microg/kg of thimerosal was injected and peaked at 10 h. MT-2 was detected in the cerebellum only at 10 h. In the cerebrum, little MT-1 protein was detected at 10 and 24 h, and there were no peaks of MT-2 protein in the cerebrum. In conclusion, MT-1 and MT-3 mRNAs but not MT-2 mRNA are easily expressed in the cerebellum rather than in the cerebrum by the injection of low-dose thimerosal. It is thought that the cerebellum is a sensitive organ against thimerosal. As a result of the present findings, in combination with the brain pathology observed in patients diagnosed with autism, the present study helps to support the possible biological plausibility for how low-dose exposure to mercury from thimerosal-containing vaccines may be associated with autism.

Correlation of sex ratio at birth with health and socioeconomic indicators.

PubMed

Grech, Victor

2018-03-01

The sex ratio at birth (male divided by total live births: M/T) has been mooted as a potential sentinel health indicator. Several metrics indicate individual countries' health and socioeconomic status. In this study, in all available countries (where such data was accessible), M/T and these indicators were compared in order to ascertain whether better (vis-à-vis health and socioeconomic status) levels of these indicators were associated with higher M/T in available countries. The following were obtained (by country) from various sources: M/T, infant mortality rate, under 5 years mortality rate, fertility rate, Human Development Index, gross domestic product per capita, life expectancy for both sexes, females, males, as well as both sexes Health Adjusted Life Expectancy (HALE). Pearson correlation was performed comparing M/T and these indicators. Despite weak correlation values, all except for the Human Development Index (HDI) correlated with M/T at statistically significant levels. A decrease in mortality and an increase in life expectancy and GDP/capita are indicators of socioeconomic wellbeing. In this study, mortality was negatively correlated with M/T. Life expectancy and GDP/capita were both positively correlated with M/T, indicating that M/T may also serve as a surrogate health indicator, and incidentally, also supporting the Trivers-Willard hypothesis. Improving economies lead to increasing education, which in turns tends to lower fertility rate in association with a declining M/T. In conclusion, the global correlation of health and socioeconomic indicators with M/T suggests that M/T may be a useful sentinel health indicator. Copyright © 2018 Elsevier B.V. All rights reserved.

Metallothioneins regulate the adipogenic differentiation of 3T3-L1 cells via the insulin signaling pathway

PubMed Central

Toriuchi, Yuriko; Aki, Yuka; Mizuno, Yuto; Kawakami, Takashige; Nakaya, Tomoko; Sato, Masao; Suzuki, Shinya

2017-01-01

Knockout of metallothionein (MT) genes contributes to a heavier body weight in early life and the potential to become obese through the intake of a high fat diet (HFD) in mice. It has thus been suggested that MT genes regulate the formation of adipose tissue, which would become the base for later HFD-induced obesity. We evaluated the fat pads of mice during the lactation stage. The fat mass and adipocyte size of MT1 and MT2 knockout mice were greater than those of wild type mice. Next, we assayed the ability of small interfering RNA (siRNA) to silence MT genes in the 3T3-L1 cell line. The expressions of MT1 and MT2 genes were transiently upregulated during adipocyte differentiation, and the siRNA pretreatment led to the suppression of the expression of both MT mRNAs and proteins. The MT siRNA promoted lipid accumulation in adipocytes and caused proliferation of post-confluent preadipocytes; these effects were suppressed by an inhibitor of phosphatidylinositol 3-kinase (LY294002). In addition, MT siRNA promoted insulin-stimulated phosphorylation of Akt, a downstream kinase of the insulin signaling pathway. Enhanced lipid accumulation in 3T3-L1 cells resulting from MT-gene silencing was inhibited by pretreatment with an antioxidant, N-acetylcysteine, used as a substitute for antioxidant protein MTs. These results suggest that interference in MT expression enhanced the activation of the insulin signaling pathway, resulting in higher lipid accumulation in 3T3-L1 adipocytes. PMID:28426713

Diagnostic utility of daytime salivary melatonin levels in Smith-Magenis syndrome.

PubMed

Chik, Constance L; Rollag, Mark D; Duncan, Wallace C; Smith, Ann C M

2010-01-01

An inverted circadian rhythm of melatonin (MT) likely contributes to the sleep disturbance in patients with Smith-Magenis syndrome (SMS). Plasma MT levels have documented this altered rhythm, but daytime levels of salivary MT has not been determined. Daytime measures of salivary MT might have utility in home/outpatient settings for assessing MT levels in undiagnosed patients with clinical features of SMS. The objective of this study was to determine the utility of daytime salivary MT as a diagnostic test in SMS. Thirty individuals with confirmed SMS [28 with del 17p11.2 and 2 with the retinoic acid induced 1 (RAI1) gene mutation] and five controls were studied. Single or serial daytime salivary MT levels were measured. The mean midday salivary MT level was 79.0 pg/ml in SMS patients, compared with 16.3 pg/ml in controls, with nine patients having values similar to controls. The median MT level in SMS patients was 49.0 pg/ml (first and third quartile values = 15.5 and 106.8 pg/ml). Twenty-six (90%) of 29 patients had at least one MT value >15.5 pg/ml, including 70 (78%) of 90 samples from patients with del 17p11.2 and one (20%) of five samples from the two patients with the RAI1 mutation. Neither the pattern of medication use nor age had an effect on daytime salivary MT levels. Although most SMS patients had elevated daytime salivary MT levels, multiple sampling appears necessary to distinguish patients with SMS from other conditions.

The Mitochondrial Genome Impacts Respiration but Not Fermentation in Interspecific Saccharomyces Hybrids

PubMed Central

Rigoulet, Michel; Salin, Benedicte; Masneuf-Pomarede, Isabelle; de Vienne, Dominique; Sicard, Delphine; Bely, Marina; Marullo, Philippe

2013-01-01

In eukaryotes, mitochondrial DNA (mtDNA) has high rate of nucleotide substitution leading to different mitochondrial haplotypes called mitotypes. However, the impact of mitochondrial genetic variant on phenotypic variation has been poorly considered in microorganisms because mtDNA encodes very few genes compared to nuclear DNA, and also because mitochondrial inheritance is not uniparental. Here we propose original material to unravel mitotype impact on phenotype: we produced interspecific hybrids between S. cerevisiae and S. uvarum species, using fully homozygous diploid parental strains. For two different interspecific crosses involving different parental strains, we recovered 10 independent hybrids per cross, and allowed mtDNA fixation after around 80 generations. We developed PCR-based markers for the rapid discrimination of S. cerevisiae and S. uvarum mitochondrial DNA. For both crosses, we were able to isolate fully isogenic hybrids at the nuclear level, yet possessing either S. cerevisiae mtDNA (Sc-mtDNA) or S. uvarum mtDNA (Su-mtDNA). Under fermentative conditions, the mitotype has no phenotypic impact on fermentation kinetics and products, which was expected since mtDNA are not necessary for fermentative metabolism. Alternatively, under respiratory conditions, hybrids with Sc-mtDNA have higher population growth performance, associated with higher respiratory rate. Indeed, far from the hypothesis that mtDNA variation is neutral, our work shows that mitochondrial polymorphism can have a strong impact on fitness components and hence on the evolutionary fate of the yeast populations. We hypothesize that under fermentative conditions, hybrids may fix stochastically one or the other mt-DNA, while respiratory environments may increase the probability to fix Sc-mtDNA. PMID:24086452

Age-related decline in mitochondrial DNA copy number in isolated human pancreatic islets.

PubMed

Cree, L M; Patel, S K; Pyle, A; Lynn, S; Turnbull, D M; Chinnery, P F; Walker, M

2008-08-01

Pancreatic beta cell function has been shown to decline with age in man. Depletion of mitochondrial DNA (mtDNA) copy number is associated with impaired insulin secretion in pancreatic beta cell lines, and decreased mtDNA copy number has been observed with age in skeletal muscle in man. We investigated whether mtDNA copy number decreases with age in human pancreatic beta cells, which might in turn contribute to the age-related decline in insulin secretory capacity. We quantified mtDNA copy number in isolated human islet preparations from 15 pancreas donors aged between 17 and 75 years. Islets (n = 20) were individually hand-picked and pooled from each donor isolate for the quantification of mtDNA copy number and deleted mtDNA (%), which were determined using real-time PCR methods. There was a significant negative correlation between mtDNA copy number and islet donor age (r = -0.53, p = 0.044). mtDNA copy number was significantly decreased in islet preparations from donors aged > or =50 years (n = 8) compared with those aged <50 years (n = 7) (median [interquartile range]: 418 [236-503] vs 596 [554-729] mtDNA copy number/diploid genome; p = 0.032). None of the islet preparations harboured high levels of deleted mtDNA affecting the major arc. Given the correlation between mtDNA content and respiratory chain activity, the age-related decrease in mtDNA copy number that we observed in human pancreatic islet preparations may contribute to the age-dependent decline in pancreatic beta cell insulin secretory capacity.

Diverse Peptide Hormones Affecting Root Growth Identified in the Medicago truncatula Secreted Peptidome.

PubMed

Patel, Neha; Mohd-Radzman, Nadiatul A; Corcilius, Leo; Crossett, Ben; Connolly, Angela; Cordwell, Stuart J; Ivanovici, Ariel; Taylor, Katia; Williams, James; Binos, Steve; Mariani, Michael; Payne, Richard J; Djordjevic, Michael A

2018-01-01

Multigene families encoding diverse secreted peptide hormones play important roles in plant development. A need exists to efficiently elucidate the structures and post-translational-modifications of these difficult-to-isolate peptide hormones in planta so that their biological functions can be determined. A mass spectrometry and bioinformatics approach was developed to comprehensively analyze the secreted peptidome of Medicago hairy root cultures and xylem sap. We identified 759 spectra corresponding to the secreted products of twelve peptide hormones including four CEP ( C -TERMINALLY E NCODED P EPTIDE), two CLE ( CL V3/ E NDOSPERM SURROUNDING REGION RELATED) and six XAP ( X YLEM SAP A SSOCIATED P EPTIDE) peptides. The MtCEP1, MtCEP2, MtCEP5 and MtCEP8 peptides identified differed in post-translational-modifications. Most were hydroxylated at conserved proline residues but some MtCEP1 derivatives were tri-arabinosylated. In addition, many CEP peptides possessed unexpected N - and C -terminal extensions. The pattern of these extensions suggested roles for endo- and exoproteases in CEP peptide maturation. Longer than expected, hydroxylated and homogeneously modified mono- and tri-arabinosylated CEP peptides corresponding to their in vivo structures were chemically synthesized to probe the effect of these post-translational-modifications on function. The ability of CEP peptides to elevate root nodule number was increased by hydroxylation at key positions. MtCEP1 peptides with N -terminal extensions or with tri-arabinosylation modification, however, were unable to impart increased nodulation. The MtCLE5 and MtCLE17 peptides identified were of precise size, and inhibited main root growth and increased lateral root number. Six XAP peptides, each beginning with a conserved DY sulfation motif, were identified including MtXAP1a, MtXAP1b, MtXAP1c, MtXAP3, MtXAP5 and MtXAP7. MtXAP1a and MtXAP5 inhibited lateral root emergence. Transcriptional analyses demonstrated peptide hormone gene expression in the root vasculature and tip. Since hairy roots can be induced on many plants, their corresponding root cultures may represent ideal source materials to efficiently identify diverse peptide hormones in vivo in a broad range of species. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Mitochondrial dysfunction in migraine.

PubMed

Yorns, William R; Hardison, H Huntley

2013-09-01

Migraine is the most frequent type of headache in children. In the 1980s, scientists first hypothesized a connection between migraine and mitochondrial (mt) disorders. More recent studies have suggested that at least some subtypes of migraine may be related to a mt defect. Different types of evidence support a relationship between mitochondria (mt) and migraine: (1) Biochemical evidence: Abnormal mt function translates into high intracellular penetration of Ca(2+), excessive production of free radicals, and deficient oxidative phosphorylation, which ultimately causes energy failure in neurons and astrocytes, thus triggering migraine mechanisms, including spreading depression. The mt markers of these events are low activity of superoxide dismutase, activation of cytochrome-c oxidase and nitric oxide, high levels of lactate and pyruvate, and low ratios of phosphocreatine-inorganic phosphate and N-acetylaspartate-choline. (2) Morphologic evidence: mt abnormalities have been shown in migraine sufferers, the most characteristic ones being direct observation in muscle biopsy of ragged red and cytochrome-c oxidase-negative fibers, accumulation of subsarcolemmal mt, and demonstration of giant mt with paracrystalline inclusions. (3) Genetic evidence: Recent studies have identified specific mutations responsible for migraine susceptibility. However, the investigation of the mtDNA mutations found in classic mt disorders (mt encephalomyopathy with lactic acidosis and stroke-like episodes, myoclonus epilepsy with ragged red fibers, Kearns-Sayre syndrome, and Leber hereditary optic neuropathy) has not demonstrated any association. Recently, 2 common mtDNA polymorphisms (16519C→T and 3010G→A) have been associated with pediatric cyclic vomiting syndrome and migraine. Also, POLG mutations (eg, p.T851 A, p.N468D, p.Y831C, p.G517V, and p.P163S) can cause disease through impaired replication of mtDNA, including migraine. Further studies to investigate the relationship between mtDNA and migraine will require very large sample sizes to obtain statistically significant results. (4) Therapeutic evidence: Several agents that have a positive effect on mt metabolism have shown to be effective in the treatment of migraines. The agents include riboflavin (B2), coenzyme Q10, magnesium, niacin, carnitine, topiramate, and lipoic acid. Further study is warranted to learn how mt interact with other factors to cause migraines. This will facilitate the development of new and more specific treatments that will reduce the frequency or severity or both of this disease. © 2013 Published by Elsevier Inc.

Kinetic changes in tetanic Ca2+ transients in enzymatically dissociated muscle fibres under repetitive stimulation

PubMed Central

Calderón, Juan C; Bolaños, Pura; Caputo, Carlo

2011-01-01

Abstract We used enzymatically dissociated flexor digitorum brevis (FDB) and soleus fibres loaded with the fast Ca2+ dye Magfluo-4 AM, and adhered to Laminin, to test whether repetitive stimulation induces progressive changes in the kinetics of Ca2+ release and reuptake in a fibre-type-dependent fashion. We applied a protocol of tetani of 350 ms, 100 Hz, every 4 s to reach a mean amplitude reduction of 25% of the first peak. Morphology type I (MT-I) and morphology type II (MT-II) fibres underwent a total of 96 and 52.8 tetani (P < 0.01 between groups), respectively. The MT-II fibres (n = 18) showed significant reductions of the amplitude (19%), an increase in rise time (8.5%) and a further reduction of the amplitude/rise time ratio (25.5%) of the first peak of the tetanic transient after 40 tetani, while MT-I fibres (n = 5) did not show any of these changes. However, both fibre types showed significant reductions in the maximum rate of rise of the first peak after 40 tetani. Two subpopulations among the MT-II fibres could be distinguished according to Ca2+ reuptake changes. Fast-fatigable MT-II fibres (fMT-II) showed an increase of 32.2% in the half-width value of the first peak, while for fatigue-resistant MT-II fibres (rMT-II), the increase amounted to 6.9%, both after 40 tetani. Significant and non-significant increases of 36.4% and 11.9% in the first time constant of decay (t1) values were seen after 40 tetani in fMT-II and rMT-II fibres, respectively. MT-I fibres did not show kinetic changes in any of the Ca2+ reuptake variables. All changes were reversed after an average recovery of 7.5 and 15.4 min for MT-I and MT-II fibres, respectively. Further experiments ruled out the possibility that the differences in the kinetic changes of the first peak of the Ca2+ transients between fibres MT-I and MT-II could be related to the inactivation of Ca2+ release mechanism. In conclusion, we established a model of enzymatically dissociated fibres, loaded with Magfluo-4 and adhered to Laminin, to study muscle fatigue and demonstrated fibre-type-dependent, fatigue-induced kinetic changes in both Ca2+ release and reuptake. PMID:21878526

Mitochondrial Nucleoid: Shield and Switch of the Mitochondrial Genome

PubMed Central

2017-01-01

Mitochondria preserve very complex and distinctively unique machinery to maintain and express the content of mitochondrial DNA (mtDNA). Similar to chromosomes, mtDNA is packaged into discrete mtDNA-protein complexes referred to as a nucleoid. In addition to its role as a mtDNA shield, over 50 nucleoid-associated proteins play roles in mtDNA maintenance and gene expression through either temporary or permanent association with mtDNA or other nucleoid-associated proteins. The number of mtDNA(s) contained within a single nucleoid is a fundamental question but remains a somewhat controversial issue. Disturbance in nucleoid components and mutations in mtDNA were identified as significant in various diseases, including carcinogenesis. Significant interest in the nucleoid structure and its regulation has been stimulated in relation to mitochondrial diseases, which encompass diseases in multicellular organisms and are associated with accumulation of numerous mutations in mtDNA. In this review, mitochondrial nucleoid structure, nucleoid-associated proteins, and their regulatory roles in mitochondrial metabolism are briefly addressed to provide an overview of the emerging research field involving mitochondrial biology. PMID:28680532

Thermostability of native and pegylated Myceliophthora thermophila laccase in aqueous and mixed solvents.

PubMed

López-Cruz, J I; Viniegra-Gonzalez, G; Hernández-Arana, A

2006-01-01

A commercial preparation of laccase (EC 1.10.3.2), cloned from Myceliophthora thermophila and expressed in Aspergillus oryzae (MtL), was purified and modified by conjugation with poly(ethylene glycol) (M(r) = 5000) and is labeled PEG-MtL. Native enzyme was found to have a molecular mass of 80 kDa, as determined by gel filtration, and 110 kDa, by SDS-PAGE. The oxidative dimerization of 2,6-dimethoxyphenol (DMP) to produce the corresponding dibenzoquinone was catalyzed by MtL in a manner comparable to that for a diffusion-controlled reaction (k(cat)/K(M) approximately = 10(8) M(-)(1) s(-)(1) and E(a) approximately = 18 kJ M(-)(1)). PEG-MtL was found, by TNBS titration, to have blocked 54% of lysine groups; its hydrodynamic and charge properties were different from those of MtL. Catalytic efficiency (k(cat)/K(M)) of PEG-MtL was similar to that of MtL with DMP as substrate; however, k(cat)/K(M) was 2-fold reduced for the reaction in which 2',2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) is oxidized to form a radical cation. E(a) values were similar in both enzyme preparations when assayed in buffered solutions. Far-UV CD spectra were similar for MtL and PEG-MtL and consistent with a protein rich in beta-sheet structure with negligible content of alpha-helices. A blue shift of near-UV CD spectrum for PEG-MtL as compared to MtL was consistent with the decreased polarity of the tyrosyl side chains upon PEG conjugation. Also the blue band of the copper active site was shifted from lambda approximately 610 nm (MtL) to lambda approximately 575 nm (PEG-MtL). Scanning microcalorimetry showed small denaturation enthalpies (6.3 and 7.5 J g(-)(1) for MtL and PEG-MtL, respectively), indicating the high stability of the beta-sheet folding pattern of laccases. However, PEG-MtL proved to be more stable, its half-denaturation temperature being 2 degrees C higher than that of MtL. In 30% alcohol, pegylated laccase showed slower enzyme-activity decay rates than the unmodified enzyme; this behavior was caused by a decrease in the activation entropy of the denaturation reaction. Results can be explained by entropic stabilization by PEG conjugation because of the restricted motion of some surface amino acid side chains, which results in a more stable active site.

44 CFR 15.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING.... Weather means the Mt. Weather Emergency Operations Center, Bluemont, Virginia. Mt. Weather Executive Director means the Executive Director of the Mt. Weather Emergency Operations Center. NETC means the...

44 CFR 15.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY.... Weather means the Mt. Weather Emergency Operations Center, Bluemont, Virginia. Mt. Weather Executive Director means the Executive Director of the Mt. Weather Emergency Operations Center. NETC means the...

44 CFR 15.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY.... Weather means the Mt. Weather Emergency Operations Center, Bluemont, Virginia. Mt. Weather Executive Director means the Executive Director of the Mt. Weather Emergency Operations Center. NETC means the...

44 CFR 15.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY.... Weather means the Mt. Weather Emergency Operations Center, Bluemont, Virginia. Mt. Weather Executive Director means the Executive Director of the Mt. Weather Emergency Operations Center. NETC means the...

44 CFR 15.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SECURITY GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY.... Weather means the Mt. Weather Emergency Operations Center, Bluemont, Virginia. Mt. Weather Executive Director means the Executive Director of the Mt. Weather Emergency Operations Center. NETC means the...

WSJointInv2D-MT-DCR: An efficient joint two-dimensional magnetotelluric and direct current resistivity inversion

NASA Astrophysics Data System (ADS)

Amatyakul, Puwis; Vachiratienchai, Chatchai; Siripunvaraporn, Weerachai

2017-05-01

An efficient joint two-dimensional direct current resistivity (DCR) and magnetotelluric (MT) inversion, referred to as WSJointInv2D-MT-DCR, was developed with FORTRAN 95 based on the data space Occam's inversion algorithm. Our joint inversion software can be used to invert just the MT data or the DCR data, or invert both data sets simultaneously to get the electrical resistivity structures. Since both MT and DCR surveys yield the same resistivity structures, the two data types enhance each other leading to a better interpretation. Two synthetic and a real field survey are used here to demonstrate that the joint DCR and MT surveys can help constrain each other to reduce the ambiguities occurring when inverting the DCR or MT alone. The DCR data increases the lateral resolution of the near surface structures while the MT data reveals the deeper structures. When the MT apparent resistivity suffers from the static shift, the DCR apparent resistivity can serve as a replacement for the estimation of the static shift factor using the joint inversion. In addition, we also used these examples to show the efficiency of our joint inversion code. With the availability of our new joint inversion software, we expect the number of joint DCR and MT surveys to increase in the future.

Snow cover correlation between Mt. Villarrica and Mt. Lliama in Chile

NASA Astrophysics Data System (ADS)

Kim, Jeong-Cheol; Park, Sung-Hwan; Jung, Hyung-Sup

2014-11-01

The Southern Volcanic Zone (SVZ) of Chile consists of many volcanoes, and all of the volcanoes are covered with snow at the top of mountain. Monitoring snow cover variations in these regions can give us a key parameter in order to understand the mechanisms of volcanic activity. In this study, we investigate on the volcanic activity and snow cover interaction from snow cover area mapping, snow-line extraction. The study areas cover Mt. Villarrica and Mt. Llaima, Chile. Both of them are most active volcanos in SVZ. Sixty Landsat TM and Landsat ETM+ images are used for observing snow cover variations of Mt. Villarrica and Mt. Llaima, spanning the 25 years from September 1986 to February 2011. Results show that snow cover area between volcanic activity and non-activity are largely changed from 42.84 km2 to 13.41 km2, temporarily decreased 79% at the Mt. Villarrica and from 28.98 km2 to 3.82 km2, temporarily decreased 87% at the Mt. Villarrica. The snow line elevation of snow cover retreated by approximately 260 m from 1,606m to 1,871 m at the Mt. Villarrica, approximately 266m from 1,741m to 2,007m at the Mt. Llaima. The results show that there are definitely correlations between snow cover and volcanic activity.

Novel mitochondrial gene content and gene arrangement indicate illegitimate inter-mtDNA recombination in the chigger mite, Leptotrombidium pallidum.

PubMed

Shao, Renfu; Mitani, Harumi; Barker, Stephen C; Takahashi, Mamoru; Fukunaga, Masahito

2005-06-01

To better understand the evolution of mitochondrial (mt) genomes in the Acari (mites and ticks), we sequenced the mt genome of the chigger mite, Leptotrombidium pallidum (Arthropoda: Acari: Acariformes). This genome is highly rearranged relative to that of the hypothetical ancestor of the arthropods and the other species of Acari studied. The mt genome of L. pallidum has two genes for large subunit rRNA, a pseudogene for small subunit rRNA, and four nearly identical large noncoding regions. Nineteen of the 22 tRNAs encoded by this genome apparently lack either a T-arm or a D-arm. Further, the mt genome of L. pallidum has two distantly separated sections with identical sequences but opposite orientations of transcription. This arrangement cannot be accounted for by homologous recombination or by previously known mechanisms of mt gene rearrangement. The most plausible explanation for the origin of this arrangement is illegitimate inter-mtDNA recombination, which has not been reported previously in animals. In light of the evidence from previous experiments on recombination in nuclear and mt genomes of animals, we propose a model of illegitimate inter-mtDNA recombination to account for the novel gene content and gene arrangement in the mt genome of L. pallidum.

Altering the Mitochondrial Fatty Acid Synthesis (mtFASII) Pathway Modulates Cellular Metabolic States and Bioactive Lipid Profiles as Revealed by Metabolomic Profiling

PubMed Central

Clay, Hayley B.; Parl, Angelika K.; Mitchell, Sabrina L.; Singh, Larry; Bell, Lauren N.; Murdock, Deborah G.

2016-01-01

Despite the presence of a cytosolic fatty acid synthesis pathway, mitochondria have retained their own means of creating fatty acids via the mitochondrial fatty acid synthesis (mtFASII) pathway. The reason for its conservation has not yet been elucidated. Therefore, to better understand the role of mtFASII in the cell, we used thin layer chromatography to characterize the contribution of the mtFASII pathway to the fatty acid composition of selected mitochondrial lipids. Next, we performed metabolomic analysis on HeLa cells in which the mtFASII pathway was either hypofunctional (through knockdown of mitochondrial acyl carrier protein, ACP) or hyperfunctional (through overexpression of mitochondrial enoyl-CoA reductase, MECR). Our results indicate that the mtFASII pathway contributes little to the fatty acid composition of mitochondrial lipid species examined. Additionally, loss of mtFASII function results in changes in biochemical pathways suggesting alterations in glucose utilization and redox state. Interestingly, levels of bioactive lipids, including lysophospholipids and sphingolipids, directly correlate with mtFASII function, indicating that mtFASII may be involved in the regulation of bioactive lipid levels. Regulation of bioactive lipid levels by mtFASII implicates the pathway as a mediator of intracellular signaling. PMID:26963735

Early zygote-specific nuclease in mitochondria of the true slime mold Physarum polycephalum.

PubMed

Moriyama, Yohsuke; Yamazaki, Tomokazu; Nomura, Hideo; Sasaki, Narie; Kawano, Shigeyuki

2005-11-01

The active, selective digestion of mtDNA from one parent is a possible molecular mechanism for the uniparental inheritance of mtDNA. In Physarum polycephalum, mtDNA is packed by DNA-binding protein Glom, which packs mtDNA into rod-shaped mt-nucleoids. After the mating, mtDNA from one parent is selectively digested, and the Glom began to disperse. Dispersed Glom was retained for at least 6 h after mtDNA digestion, but disappeared completely by about 12 h after mixing two strains. We identified two novel nucleases using DNA zymography with native-PAGE and SDS-PAGE. One is a Ca2+-dependent, high-molecular-weight nuclease complex (about 670 kDa), and the other is a Mn2+-dependent, high-molecular-weight nuclease complex (440-670 kDa); the activity of the latter was detected as a Mn2+-dependent, 13-kDa DNase band on SDS-PAGE. All mitochondria isolated from myxamoebae had mt-nucleoids, whereas half of the mitochondria isolated from the zygotes at 12 h after mixing had lost the mt-nucleoids. The activity of the Mn2+-dependent nuclease in the isolated mitochondria was detected at least 8 h after mixing of two strains. The timing and localization of the Mn2+-dependent DNase activity matched the selective digestion of mtDNA.

APC functions at the centrosome to stimulate microtubule growth.

PubMed

Lui, Christina; Ashton, Cahora; Sharma, Manisha; Brocardo, Mariana G; Henderson, Beric R

2016-01-01

The adenomatous polyposis coli (APC) tumor suppressor is multi-functional. APC is known to localize at the centrosome, and in mitotic cells contributes to formation of the mitotic spindle. To test whether APC contributes to nascent microtubule (MT) growth at interphase centrosomes, we employed MT regrowth assays in U2OS cells to measure MT assembly before and after nocodazole treatment and release. We showed that siRNA knockdown of full-length APC delayed both initial MT aster formation and MT elongation/regrowth. In contrast, APC-mutant SW480 cancer cells displayed a defect in MT regrowth that was unaffected by APC knockdown, but which was rescued by reconstitution of full-length APC. Our findings identify APC as a positive regulator of centrosome MT initial assembly and suggest that this process is disrupted by cancer mutations. We confirmed that full-length APC associates with the MT-nucleation factor γ-tubulin, and found that the APC cancer-truncated form (1-1309) also bound to γ-tubulin through APC amino acids 1-453. While binding to γ-tubulin may help target APC to the site of MT nucleation complexes, additional C-terminal sequences of APC are required to stimulate and stabilize MT growth. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma

PubMed Central

Nickerson, John M.; Gao, Feng-juan; Sun, Zhongmou; Chen, Xin-ya; Zhang, Shu-jie; Gao, Feng; Chen, Jun-yi; Luo, Yi; Wang, Yan; Sun, Xing-huai

2015-01-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. PMID:25478814

Examining Dark Triad traits in relation to mental toughness and physical activity in young adults

PubMed Central

Sabouri, Sarah; Gerber, Markus; Sadeghi Bahmani, Dena; Lemola, Sakari; Clough, Peter J; Kalak, Nadeem; Shamsi, Mahin; Holsboer-Trachsler, Edith; Brand, Serge

2016-01-01

Objective The Dark Triad (DT) describes a set of three closely related personality traits: Machiavellianism, narcissism, and psychopathy. Mental toughness (MT) refers to a psychological construct combining confidence, commitment, control, and challenge. High MT is related to greater physical activity (PA) and, relative to men, women have lower MT scores. The aims of the present study were 1) to investigate the association between DT, MT, and PA, and 2) to compare the DT, MT, and PA scores of men and women. Methods A total of 341 adults (M=29 years; 51.6% women; range: 18–37 years) took part in the study. Participants completed a series of questionnaires assessing DT, MT, and PA. Results Machiavellianism, narcissism, and psychopathy were all significantly associated with higher MT scores (rs =0.45, 0.50, and 0.20, respectively). DT traits and MT were associated with more vigorous PA. Compared to men, women participants had lower scores for DT traits (overall score and psychopathy), while no differences were found for MT or PA in both sexes. Conclusion DT traits, high MT, and vigorous PA are interrelated. This pattern of results might explain why, for instance, successful professional athletes can at the same time be tough and ruthless. PMID:26869790

Methylation of arsenic by recombinant human wild-type arsenic (+ 3 oxidation state) methyltransferase and its methionine 287 threonine (M287T) polymorph: Role of glutathione

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Lan; Saunders, R. Jesse; Drobná, Zuzana

2012-10-01

Arsenic (+ 3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the pathway for methylation of arsenicals. A common polymorphism in the AS3MT gene that replaces a threonyl residue in position 287 with a methionyl residue (AS3MT/M287T) occurs at a frequency of about 10% among populations worldwide. Here, we compared catalytic properties of recombinant human wild-type (wt) AS3MT and AS3MT/M287T in reaction mixtures containing S-adenosylmethionine, arsenite (iAs{sup III}) or methylarsonous acid (MAs{sup III}) as substrates and endogenous or synthetic reductants, including glutathione (GSH), a thioredoxin reductase (TR)/thioredoxin (Trx)/NADPH reducing system, or tris (2-carboxyethyl) phosphine hydrochloride (TCEP). With either TR/Trx/NADPHmore » or TCEP, wtAS3MT or AS3MT/M287T catalyzed conversion of iAs{sup III} to MAs{sup III}, methylarsonic acid (MAs{sup V}), dimethylarsinous acid (DMAs{sup III}), and dimethylarsinic acid (DMAs{sup V}); MAs{sup III} was converted to DMAs{sup III} and DMAs{sup V}. Although neither enzyme required GSH to support methylation of iAs{sup III} or MAs{sup III}, addition of 1 mM GSH decreased K{sub m} and increased V{sub max} estimates for either substrate in reaction mixtures containing TR/Trx/NADPH. Without GSH, V{sub max} and K{sub m} values were significantly lower for AS3MT/M287T than for wtAS3MT. In the presence of 1 mM GSH, significantly more DMAs{sup III} was produced from iAs{sup III} in reactions catalyzed by the M287T variant than in wtAS3MT-catalyzed reactions. Thus, 1 mM GSH modulates AS3MT activity, increasing both methylation rates and yield of DMAs{sup III}. AS3MT genotype exemplified by differences in regulation of wtAS3MT and AS3MT/M287T-catalyzed reactions by GSH may contribute to differences in the phenotype for arsenic methylation and, ultimately, to differences in the disease susceptibility in individuals chronically exposed to inorganic arsenic. -- Highlights: ► Human AS3MT and AS3MT(M287T) require a dithiol reductant for optimal activity. ► Both enzymes methylate arsenite to tri- and pentavalent methylated metabolites. ► Neither enzyme requires glutathione (GSH) to methylate arsenite or methylarsonite. ► However, in presence of a dithiol addition of 1 mM GSH increases methylation rates. ► In presence of 1 mM GSH, AS3MT(M287T) produces more dimethylarsinite than AS3MT.« less

Effects of multitasking-training on gray matter structure and resting state neural mechanisms

PubMed Central

Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Hashizume, Hiroshi; Sekiguchi, Atsushi; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Sassa, Yuko; Kawashima, Ryuta

2014-01-01

Multitasking (MT) constitutes engaging in two or more cognitive activities at the same time. MT-training improves performance on untrained MT tasks and alters the functional activity of the brain during MT. However, the effects of MT-training on neural mechanisms beyond MT-related functions are not known. We investigated the effects of 4 weeks of MT-training on regional gray matter volume (rGMV) and functional connectivity during rest (resting-FC) in young human adults. MT-training was associated with increased rGMV in three prefrontal cortical regions (left lateral rostral prefrontal cortex (PFC), dorsolateral PFC (DLPFC), and left inferior frontal junction), the left posterior parietal cortex, and the left temporal and lateral occipital areas as well as decreased resting-FC between the right DLPFC and an anatomical cluster around the ventral anterior cingulate cortex (ACC). Our findings suggest that participation in MT-training is as a whole associated with task-irrelevant plasticity (i.e., neural changes are not limited to certain specific task conditions) in regions and the network that are assumed to play roles in MT as well as diverse higher-order cognitive functions. We could not dissociate the effects of each task component and the diverse cognitive processes involved in MT because of the nature of the study, and these remain to be investigated. Hum Brain Mapp 35:3646–3660, 2014. © 2013 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:24343872

Age-Related Mitochondrial DNA Depletion and the Impact on Pancreatic Beta Cell Function

PubMed Central

Nile, Donna L.; Brown, Audrey E.; Kumaheri, Meutia A.; Blair, Helen R.; Heggie, Alison; Miwa, Satomi; Cree, Lynsey M.; Payne, Brendan; Chinnery, Patrick F.; Brown, Louise; Gunn, David A.; Walker, Mark

2014-01-01

Type 2 diabetes is characterised by an age-related decline in insulin secretion. We previously identified a 50% age-related decline in mitochondrial DNA (mtDNA) copy number in isolated human islets. The purpose of this study was to mimic this degree of mtDNA depletion in MIN6 cells to determine whether there is a direct impact on insulin secretion. Transcriptional silencing of mitochondrial transcription factor A, TFAM, decreased mtDNA levels by 40% in MIN6 cells. This level of mtDNA depletion significantly decreased mtDNA gene transcription and translation, resulting in reduced mitochondrial respiratory capacity and ATP production. Glucose-stimulated insulin secretion was impaired following partial mtDNA depletion, but was normalised following treatment with glibenclamide. This confirms that the deficit in the insulin secretory pathway precedes K+ channel closure, indicating that the impact of mtDNA depletion is at the level of mitochondrial respiration. In conclusion, partial mtDNA depletion to a degree comparable to that seen in aged human islets impaired mitochondrial function and directly decreased insulin secretion. Using our model of partial mtDNA depletion following targeted gene silencing of TFAM, we have managed to mimic the degree of mtDNA depletion observed in aged human islets, and have shown how this correlates with impaired insulin secretion. We therefore predict that the age-related mtDNA depletion in human islets is not simply a biomarker of the aging process, but will contribute to the age-related risk of type 2 diabetes. PMID:25532126

Mindfulness training increases cooperative decision making in economic exchanges: Evidence from fMRI.

PubMed

Kirk, Ulrich; Gu, Xiaosi; Sharp, Carla; Hula, Andreas; Fonagy, Peter; Montague, P Read

2016-09-01

Emotions have been shown to exert influences on decision making during economic exchanges. Here we investigate the underlying neural mechanisms of a training regimen which is hypothesized to promote emotional awareness, specifically mindfulness training (MT). We test the hypothesis that MT increases cooperative economic decision making using fMRI in a randomized longitudinal design involving 8weeks of either MT or active control training (CT). We find that MT results in an increased willingness to cooperate indexed by higher acceptance rates to unfair monetary offers in the Ultimatum Game. While controlling for acceptance rates of monetary offers between intervention groups, subjects in the MT and CT groups show differential brain activation patterns. Specifically, a subset of more cooperative MT subjects displays increased activation in the septal region, an area linked to social attachment, which may drive the increased willingness to express cooperative behavior in the MT cohort. Furthermore, MT resulted in attenuated activity in anterior insula compared with the CT group in response to unfair monetary offers post-training, which may suggest that MT enables greater ability to effectively regulate the anterior insula and thereby promotes social cooperation. Finally, functional connectivity analyses show a coupling between the septal region and posterior insula in the MT group, suggesting an integration of interoceptive inputs. Together, these results highlight that MT may be employed in contexts where emotional regulation is required to promote social cooperation. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of metallothionein in oncogenesis and cancer treatment.

PubMed

Bizoń, Anna; Jędryczko, Kinga; Milnerowicz, Halina

2017-02-14

Metallothionein is cysteine-rich low molecular mass protein. The involvement of MT in many physiological and pathophysiological processes such as apoptosis, proliferation, angiogenesis, and the detoxification of heavy metals suggested participation of this protein in carcinogenesis and tumor therapy. Depending on the type of tissue and classification of carcinoma various it was observed relation between MT expression and tumor type, stage, grade, poor prognosis and body resistance to radiotherapy and chemotherapy. MT in tumor cell plays important role in defense mechanism against the effect of radiation by inhibiting the processes that lead to the apoptosis. A number of studies have shown an increased expression of MT in various human tumors of larynx, pancreas, kidney, uterus and breast, whereas lower MT expression was detected in liver tumors. Variable MT expression was detected in case of thyroid, prostate, lung, stomach and central nervous system tumors. Also MT plays crucial role in the cytostatics treatment. MT can bind cis-platinum compounds and removes them from the cells, which may lead to multidrug resistance. However, the same functions of MT protect against the negative effects of chemotherapeutic treatment. It is especially important in case of heart cells. Analysis of MT expression in tumor cells may be useful in choosing method of treatment. It is difficult to determine whether increased expression of MT is only a inducing factor of the development of the carcinogenesis, its malignances and multidrug resistance, or it is a factor inhibiting the induction and development of cancer.

Age-related mitochondrial DNA depletion and the impact on pancreatic Beta cell function.

PubMed

Nile, Donna L; Brown, Audrey E; Kumaheri, Meutia A; Blair, Helen R; Heggie, Alison; Miwa, Satomi; Cree, Lynsey M; Payne, Brendan; Chinnery, Patrick F; Brown, Louise; Gunn, David A; Walker, Mark

2014-01-01

Type 2 diabetes is characterised by an age-related decline in insulin secretion. We previously identified a 50% age-related decline in mitochondrial DNA (mtDNA) copy number in isolated human islets. The purpose of this study was to mimic this degree of mtDNA depletion in MIN6 cells to determine whether there is a direct impact on insulin secretion. Transcriptional silencing of mitochondrial transcription factor A, TFAM, decreased mtDNA levels by 40% in MIN6 cells. This level of mtDNA depletion significantly decreased mtDNA gene transcription and translation, resulting in reduced mitochondrial respiratory capacity and ATP production. Glucose-stimulated insulin secretion was impaired following partial mtDNA depletion, but was normalised following treatment with glibenclamide. This confirms that the deficit in the insulin secretory pathway precedes K+ channel closure, indicating that the impact of mtDNA depletion is at the level of mitochondrial respiration. In conclusion, partial mtDNA depletion to a degree comparable to that seen in aged human islets impaired mitochondrial function and directly decreased insulin secretion. Using our model of partial mtDNA depletion following targeted gene silencing of TFAM, we have managed to mimic the degree of mtDNA depletion observed in aged human islets, and have shown how this correlates with impaired insulin secretion. We therefore predict that the age-related mtDNA depletion in human islets is not simply a biomarker of the aging process, but will contribute to the age-related risk of type 2 diabetes.

Interferon-alpha-induced changes in metallothionein expression in liver biopsies from patients with chronic hepatitis C.

PubMed

Nagamine, Takeaki; Suzuki, Keiji; Kondo, Toshihiko; Nakazato, Kyomi; Kakizaki, Satoru; Takagi, Hitoshi; Nakajima, Katuyuki

2005-08-01

An association between reactive oxygen species and liver damage has been postulated in the course of hepatitis C virus (HCV) infection. Metallothionein (MT), induced by HCV core protein and interferon (IFN), plays a role in scavenging free radicals. MT expression in liver biopsies obtained from 21 patients with chronic HCV infection before and after IFN-alpha therapy was investigated. Changes in Knodell histological activity index (HAI) scores, MT protein levels (immunohistochemistry), MT-I and MT-II messenger (m)RNA expression levels (in situ hybridization) and proliferating cell nuclear antigen (PCNA) labelling index were determined and compared in serial liver specimens. MT staining was clustered around the portal tracts with inflammatory cells and fibrosis. The pattern of MT protein before IFN-alpha therapy was similar in all patients, but was higher in IFN-sustained responders than in nonresponders after IFN-alpha therapy. HAI scores and PCNA labelling indexes were significantly reduced after IFN-alpha therapy. MT-II mRNA expression correlated positively with PCNA index before therapy and with HAI scores after therapy (P<0.05). No correlation was found between MT-I mRNA and HAI scores or PCNA index. The findings indicate that IFN-alpha-induced hepatic MT may participate in the therapeutic effects of IFN-alpha for HCV. In addition, MT-II mRNA expression may be involved in cell proliferation in the livers of patients with chronic HCV infection.

[Major rural accident: the pesticide "rain" case in Lucas do Rio Verde city - MT].

PubMed

Pignati, Wanderlei Antonio; Machado, Jorge M H; Cabral, James F

2007-01-01

The article reports the environmental accident caused by aerial pesticide spraying that reached the urban space of Lucas do Rio Verde-MT, in March 2006. It was characterized as a "major rural accident" of environmental and occupational aspects whose seriousness and extension crossed the agriculturally productive unit boundaries causing sanitary, social and environmental impact. This case study had as its objective the understanding of the social-technical scene of the accident and the monitoring process in health-environment in a research-action dynamic. The information was collected through interviews, documents and daily observation reports. It also referred to accidents, multidisciplinary and participatory analyses with the participation of local institutions of health, agriculture and environment, political and union leaderships, ranchers and farmers, the public prosecutor's office, journalists and the University. The study shows that the pesticide "use and abuse" monitoring actions have been extended to [a] "movement for the sustainable development of the region" supported by the participative monitoring and the fight for democracy and social justice in the search of a sustainable agriculture and/or environment.

African-American mitochondrial DNAs often match mtDNAs found in multiple African ethnic groups

PubMed Central

Ely, Bert; Wilson, Jamie Lee; Jackson, Fatimah; Jackson, Bruce A

2006-01-01

Background Mitochondrial DNA (mtDNA) haplotypes have become popular tools for tracing maternal ancestry, and several companies offer this service to the general public. Numerous studies have demonstrated that human mtDNA haplotypes can be used with confidence to identify the continent where the haplotype originated. Ideally, mtDNA haplotypes could also be used to identify a particular country or ethnic group from which the maternal ancestor emanated. However, the geographic distribution of mtDNA haplotypes is greatly influenced by the movement of both individuals and population groups. Consequently, common mtDNA haplotypes are shared among multiple ethnic groups. We have studied the distribution of mtDNA haplotypes among West African ethnic groups to determine how often mtDNA haplotypes can be used to reconnect Americans of African descent to a country or ethnic group of a maternal African ancestor. The nucleotide sequence of the mtDNA hypervariable segment I (HVS-I) usually provides sufficient information to assign a particular mtDNA to the proper haplogroup, and it contains most of the variation that is available to distinguish a particular mtDNA haplotype from closely related haplotypes. In this study, samples of general African-American and specific Gullah/Geechee HVS-I haplotypes were compared with two databases of HVS-I haplotypes from sub-Saharan Africa, and the incidence of perfect matches recorded for each sample. Results When two independent African-American samples were analyzed, more than half of the sampled HVS-I mtDNA haplotypes exactly matched common haplotypes that were shared among multiple African ethnic groups. Another 40% did not match any sequence in the database, and fewer than 10% were an exact match to a sequence from a single African ethnic group. Differences in the regional distribution of haplotypes were observed in the African database, and the African-American haplotypes were more likely to match haplotypes found in ethnic groups from West or West Central Africa than those found in eastern or southern Africa. Fewer than 14% of the African-American mtDNA sequences matched sequences from only West Africa or only West Central Africa. Conclusion Our database of sub-Saharan mtDNA sequences includes the most common haplotypes that are shared among ethnic groups from multiple regions of Africa. These common haplotypes have been found in half of all sub-Saharan Africans. More than 60% of the remaining haplotypes differ from the common haplotypes at a single nucleotide position in the HVS-I region, and they are likely to occur at varying frequencies within sub-Saharan Africa. However, the finding that 40% of the African-American mtDNAs analyzed had no match in the database indicates that only a small fraction of the total number of African haplotypes has been identified. In addition, the finding that fewer than 10% of African-American mtDNAs matched mtDNA sequences from a single African region suggests that few African Americans might be able to trace their mtDNA lineages to a particular region of Africa, and even fewer will be able to trace their mtDNA to a single ethnic group. However, no firm conclusions should be made until a much larger database is available. It is clear, however, that when identical mtDNA haplotypes are shared among many ethnic groups from different parts of Africa, it is impossible to determine which single ethnic group was the source of a particular maternal ancestor based on the mtDNA sequence. PMID:17038170

The Complete Mitochondrial Genome of Gossypium hirsutum and Evolutionary Analysis of Higher Plant Mitochondrial Genomes

PubMed Central

Su, Aiguo; Geng, Jianing; Grover, Corrinne E.; Hu, Songnian; Hua, Jinping

2013-01-01

Background Mitochondria are the main manufacturers of cellular ATP in eukaryotes. The plant mitochondrial genome contains large number of foreign DNA and repeated sequences undergone frequently intramolecular recombination. Upland Cotton (Gossypium hirsutum L.) is one of the main natural fiber crops and also an important oil-producing plant in the world. Sequencing of the cotton mitochondrial (mt) genome could be helpful for the evolution research of plant mt genomes. Methodology/Principal Findings We utilized 454 technology for sequencing and combined with Fosmid library of the Gossypium hirsutum mt genome screening and positive clones sequencing and conducted a series of evolutionary analysis on Cycas taitungensis and 24 angiosperms mt genomes. After data assembling and contigs joining, the complete mitochondrial genome sequence of G. hirsutum was obtained. The completed G.hirsutum mt genome is 621,884 bp in length, and contained 68 genes, including 35 protein genes, four rRNA genes and 29 tRNA genes. Five gene clusters are found conserved in all plant mt genomes; one and four clusters are specifically conserved in monocots and dicots, respectively. Homologous sequences are distributed along the plant mt genomes and species closely related share the most homologous sequences. For species that have both mt and chloroplast genome sequences available, we checked the location of cp-like migration and found several fragments closely linked with mitochondrial genes. Conclusion The G. hirsutum mt genome possesses most of the common characters of higher plant mt genomes. The existence of syntenic gene clusters, as well as the conservation of some intergenic sequences and genic content among the plant mt genomes suggest that evolution of mt genomes is consistent with plant taxonomy but independent among different species. PMID:23940520

The complete mitochondrial genome of Gossypium hirsutum and evolutionary analysis of higher plant mitochondrial genomes.

PubMed

Liu, Guozheng; Cao, Dandan; Li, Shuangshuang; Su, Aiguo; Geng, Jianing; Grover, Corrinne E; Hu, Songnian; Hua, Jinping

2013-01-01

Mitochondria are the main manufacturers of cellular ATP in eukaryotes. The plant mitochondrial genome contains large number of foreign DNA and repeated sequences undergone frequently intramolecular recombination. Upland Cotton (Gossypium hirsutum L.) is one of the main natural fiber crops and also an important oil-producing plant in the world. Sequencing of the cotton mitochondrial (mt) genome could be helpful for the evolution research of plant mt genomes. We utilized 454 technology for sequencing and combined with Fosmid library of the Gossypium hirsutum mt genome screening and positive clones sequencing and conducted a series of evolutionary analysis on Cycas taitungensis and 24 angiosperms mt genomes. After data assembling and contigs joining, the complete mitochondrial genome sequence of G. hirsutum was obtained. The completed G.hirsutum mt genome is 621,884 bp in length, and contained 68 genes, including 35 protein genes, four rRNA genes and 29 tRNA genes. Five gene clusters are found conserved in all plant mt genomes; one and four clusters are specifically conserved in monocots and dicots, respectively. Homologous sequences are distributed along the plant mt genomes and species closely related share the most homologous sequences. For species that have both mt and chloroplast genome sequences available, we checked the location of cp-like migration and found several fragments closely linked with mitochondrial genes. The G. hirsutum mt genome possesses most of the common characters of higher plant mt genomes. The existence of syntenic gene clusters, as well as the conservation of some intergenic sequences and genic content among the plant mt genomes suggest that evolution of mt genomes is consistent with plant taxonomy but independent among different species.

MEMBRANE-TYPE 1 MATRIX METALLOPROTEINASE DOWNREGULATES FIBROBLAST GROWTH FACTOR-2 BINDING TO THE CELL SURFACE AND INTRACELLULAR SIGNALING

PubMed Central

Tassone, Evelyne; Valacca, Cristina; Mignatti, Paolo

2014-01-01

Membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14), a transmembrane proteinase with an extracellular catalytic domain and a short cytoplasmic tail, degrades extracellular matrix components and controls diverse cell functions through proteolytic and non-proteolytic interactions with extracellular, intracellular and transmembrane proteins. Here we show that in tumor cells MT1-MMP downregulates fibroblast growth factor-2 (FGF-2) signaling by reducing the amount of FGF-2 bound to the cell surface with high and low affinity. FGF-2 induces weaker activation of ERK1/2 MAP kinase in MT1-MMP expressing cells than in cells devoid of MT1-MMP. This effect is abolished in cells that express proteolytically inactive MT1-MMP but persists in cells expressing MT1-MMP mutants devoid of hemopexin-like or cytoplasmic domain, showing that FGF-2 signaling is downregulated by MT1-MMP proteolytic activity. MT1-MMP expression results in downregulation of FGFR-1 and -4, and in decreased amount of cell surface-associated FGF-2. In addition, MT1-MMP strongly reduces the amount of FGF-2 bound to the cell surface with low affinity. Because FGF-2 association with low-affinity binding sites is a prerequisite for binding to its high-affinity receptors, downregulation of low-affinity binding to the cell surface results in decreased FGF-2 signaling. Consistent with this conclusion, FGF-2 induction of tumor cell migration and invasion in vitro is stronger in cells devoid of MT1-MMP than in MT1-MMP expressing cells. Thus, MT1-MMP controls FGF-2 signaling by a proteolytic mechanism that decreases the cell’s biological response to FGF-2. PMID:24986796

Significant treatment effect of adjunct music therapy to standard treatment on the positive, negative, and mood symptoms of schizophrenic patients: a meta-analysis.

PubMed

Tseng, Ping-Tao; Chen, Yen-Wen; Lin, Pao-Yen; Tu, Kun-Yu; Wang, Hung-Yu; Cheng, Yu-Shian; Chang, Yi-Chung; Chang, Chih-Hua; Chung, Weilun; Wu, Ching-Kuan

2016-01-26

Music therapy (MT) has been used as adjunct therapy for schizophrenia for decades. However, its role is still inconclusive. A recent meta-analysis demonstrated that MT for schizophrenic patients only significantly benefits negative symptoms and mood symptoms rather than positive symptoms. In addition, the association between specific characteristics of MT and the treatment effect remains unclear. The aim of this study was to update the published data and to explore the role of music therapy in adjunct treatment in schizophrenia with a thorough meta-analysis. We compared the treatment effect in schizophrenic patients with standard treatment who did and did not receive adjunct MT through a meta-analysis, and investigated the clinical characteristics of MT through meta-regression. The main finding was that the treatment effect was significantly better in the patients who received adjunct MT than in those who did not, in negative symptoms, mood symptoms, and also positive symptoms (all p < 0.05). This significance did not change after dividing the patients into subgroups of different total duration of MT, amounts of sessions, or frequency of MT. Besides, the treatment effect on the general symptoms was significantly positively associated with the whole duration of illness, indicating that MT would be beneficial for schizophrenic patients with a chronic course. Our meta-analysis highlights a significantly better treatment effect in schizophrenic patients who received MT than in those who did not, especially in those with a chronic course, regardless of the duration, frequency, or amounts of sessions of MT. These findings provide evidence that clinicians should apply MT for schizophrenic patients to alleviate disease severity.

Molecular characterization and expression profile of the melatonin receptor MT1 in the ovary of Tianzhu white yak (Bos grunniens).

PubMed

Hu, Jun Jie; Zhang, Xiao Yu; Zhang, Yong; Zhao, Xing Xu; Li, Fa Di; Tao, Jin Zhong

2017-02-01

Melatonin plays crucial roles in a wide range of ovarian physiological functions via the melatonin receptors (MRs). Structure and function of MRs have been well studied in sheep, cattle, and humans, but little information exists on the genetic characterization and function of these receptors in the ovary of the white yak. In the present study, the melatonin receptor MT1 was cloned by RT-PCR in the ovary of white yak; the MT1 cDNA fragment obtained (843bp) comprised an open reading frame (827bp) encoding a protein containing 275 residues, characterized by seven transmembrane regions and an NRY motif, two distinct amino acid replacements were found. The white yak MT1 had a 83.9-98.6% protein sequence identity with that of nine other mammals. Using RT-PCR, the expression levels of MT1, MT2, and LHR in the ovary of pregnant and non-pregnant white yaks were compared, revealing higher levels of all genes in pregnant yaks: 3.83-fold increase for MT1 (P<0.05), 1.39-fold increase for MT2, and 15.32-fold increase for LHR (P<0.05). The distribution of MT1 in yak ovaries was observed using immunohistochemistry on paraffin embedded ovarian sections: MT1 was mainly present on primordial follicles (PF), granulosa cells (GCs), oocytes, and corpus luteum (CL) cells; MT1 expression showed an increasing tendency from PF to GCs to oocytes and to large CL cells. It is suggested that melatonin and MT1 are associated with the corpus luteum function of pregnancy maintenance and follicular development during oocyte maturation in the white yak. Copyright © 2015 Elsevier Inc. All rights reserved.

MT1-MMP is a crucial promotor of synovial invasion in human rheumatoid arthritis

PubMed Central

Miller, Mary-Clare; Manning, Hugh B.; Jain, Abhilash; Troeberg, Linda; Dudhia, Jayesh; Essex, David; Sandison, Ann; Seiki, Motoharu; Nanchahal, Jagdeep; Nagase, Hideaki; Itoh, Yoshifumi

2010-01-01

Objective A hallmark of rheumatoid arthritis (RA) is invasion of the synovial pannus into cartilage and this step requires degradation of the collagen matrix. The aim of this study was to explore the role of one of the collagen-degrading matrix metalloproteinases (MMPs), membrane-type 1 MMP (MT1-MMP), in synovial pannus invasiveness. Methods Expression and localization of MT1-MMP in human RA pannus were investigated by Western blot analysis of primary synovial cells and immunohistochemistry of RA joints specimens. The functional role of MT1-MMP was analyzed by 3D collagen invasion assays and a cartilage invasion assay in the presence or absence of tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, or GM6001. The effect of adenoviral expression of a dominant negative MT1-MMP construct lacking a catalytic domain was also examined. Results MT1-MMP was highly expressed at the pannus-cartilage junction of RA joints. Freshly isolated rheumatoid synovial tissues and isolated RA synovial fibroblasts invaded into a 3D collagen matrix in an MT1-MMP-dependent manner. Invasion was blocked by TIMP-2 and GM6001, but not by TIMP-1. It was also inhibited by the over-expression of a dominant negative MT1-MMP which inhibits collagenolytic activity and proMMP-2 activation by MT1-MMP on the cell surface. Synovial fibroblasts also invaded into cartilage in an MT1-MMP-dependent manner. This process was further enhanced by removing aggrecan from the cartilage matrix. Conclusion MT1-MMP is an essential collagen-degrading proteinase during pannus invasion in human RA. Specific inhibition of MT1-MMP-dependent invasion may form a novel therapeutic strategy for RA. PMID:19248098

Influence of montmorillonites exchange capacity on the basal spacing of cation–anion organo-montmorillonites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanqin, Wu; Zepeng, Zhang, E-mail: unite508@163.com; Yunhua, Wang

Graphical abstract: This picture shows the distribution of organic modifier (CTAB and SDS) in Mt interlayer and the basal spacing changes of Mt modified by CTAB and SDS. Organic modifier molecule in Mt interlayer is more and more orderly. The basal spacing of Mt is from 1.5 nm to 5 nm as modifier added. - Highlights: • The d{sub 001} of Ca-Mt, R-Na-Mt, Na-Mt modified by CTAB and SDS can reach 5 nm. • It is easier to get cation–anion OMt with greater d{sub 001} if CEC is lower. • The organic molecules distribution in cation–anion OMt was analyzed. •more » The influence mechanism of Ca-Mt CEC on the d{sub 001} was discussed. - Abstract: With cationic and anionic surfactants cetyltrimethylammonium bromide (CTAB) and sodium dodecylsulfonate (SDS) as modifiers, Ca-montmorillonites (Ca-Mt), artificial Na-montmorillonites (R-Na-Mt) and natural Na-montmorillonites (Na-Mt) with different cation exchange capacity (CEC) were modified by solution intercalation method, respectively. Then cation–anion organo-montmorillonites (OMt) were prepared. The influence of CEC on the basal spacing of cation–anion OMt and the influence mechanism were discussed by X-ray diffraction (XRD) and zeta potential testing. The results indicate that the basal spacing of cation–anion OMt is related to CEC. For the same type montmorillonites, the basal spacing of cation–anion OMt decreases with the increase of CEC and it is easier to get cation–anion OMt with greater basal spacing when CEC is lower. Moreover, the CEC of Na-Mt has the greatest influence on the basal spacing of cation–anion OMt.« less

Re-examining overlap between tactile and visual motion responses within hMT+ and STS

PubMed Central

Jiang, Fang; Beauchamp, Michael S.; Fine, Ione

2015-01-01

Here we examine overlap between tactile and visual motion BOLD responses within the human MT+ complex. Although several studies have reported tactile responses overlapping with hMT+, many used group average analyses, leaving it unclear whether these responses were restricted to sub-regions of hMT+. Moreover, previous studies either employed a tactile task or passive stimulation, leaving it unclear whether or not tactile responses in hMT+ are simply the consequence of visual imagery. Here we carried out a replication of one of the classic papers finding tactile responses in hMT+ (Hagen et al. 2002). We mapped MT and MST in individual subjects using visual field localizers. We then examined responses to tactile motion on the arm, either presented passively or in the presence of a visual task performed at fixation designed to minimize visualization of the concurrent tactile stimulation. To our surprise, without a visual task, we found only weak tactile motion responses in MT (6% of voxels showing tactile responses) and MST (2% of voxels). With an unrelated visual task designed to withdraw attention from the tactile modality, responses in MST reduced to almost nothing (<1% regions). Consistent with previous results, we did observe tactile responses in STS regions superior and anterior to hMT+. Despite the lack of individual overlap, group averaged responses produced strong spurious overlap between tactile and visual motion responses within hMT+ that resembled those observed in previous studies. The weak nature of tactile responses in hMT+ (and their abolition by withdrawal of attention) suggests that hMT+ may not serve as a supramodal motion processing module. PMID:26123373

Increased mitochondrial DNA deletions and copy number in transfusion-dependent thalassemia

PubMed Central

Calloway, Cassandra

2016-01-01

BACKGROUND. Iron overload is the primary cause of morbidity in transfusion-dependent thalassemia. Increase in iron causes mitochondrial dysfunction under experimental conditions, but the occurrence and significance of mitochondrial damage is not understood in patients with thalassemia. METHODS. Mitochondrial DNA (mtDNA) to nuclear DNA copy number (Mt/N) and frequency of the common 4977-bp mitochondrial deletion (ΔmtDNA4977) were quantified using a quantitative PCR assay on whole blood samples from 38 subjects with thalassemia who were receiving regular transfusions. RESULTS. Compared with healthy controls, Mt/N and ΔmtDNA4977 frequency were elevated in thalassemia (P = 0.038 and P < 0.001, respectively). ΔmtDNA4977 was increased in the presence of either liver iron concentration > 15 mg/g dry-weight or splenectomy, with the highest levels observed in subjects who had both risk factors (P = 0.003). Myocardial iron (MRI T2* < 20 ms) was present in 0%, 22%, and 46% of subjects with ΔmtDNA4977 frequency < 20, 20–40, and > 40/1 × 107 mtDNA, respectively (P = 0.025). Subjects with Mt/N values below the group median had significantly lower Matsuda insulin sensitivity index (5.76 ± 0.53) compared with the high Mt/N group (9.11 ± 0.95, P = 0.008). CONCLUSION. Individuals with transfusion-dependent thalassemia demonstrate age-related increase in mtDNA damage in leukocytes. These changes are markedly amplified by splenectomy and are associated with extrahepatic iron deposition. Elevated mtDNA damage in blood cells may predict the risk of iron-associated organ damage in thalassemia. FUNDING. This project was supported by Children’s Hospital & Research Center Oakland Institutional Research Award and by the National Center for Advancing Translational Sciences, NIH, through UCSF-CTSI grant UL1 TR000004. PMID:27583305

Requirement of the Saccharomyces cerevisiae APN1 Gene for the Repair of Mitochondrial DNA Alkylation Damage

PubMed Central

Acevedo-Torres, Karina; Fonseca-Williams, Sharon; Ayala-Torres, Sylvette; Torres-Ramos, Carlos A.

2010-01-01

The Saccharomyces cerevisiae APN1 gene that participates in base excision repair has been localized both in the nucleus and the mitochondria. APN1 deficient cells (apn1Δ) show increased mutation frequencies in mitochondrial DNA (mtDNA) suggesting that APN1 is also important for mtDNA stability. To understand APN1-dependent mtDNA repair processes we studied the formation and repair of mtDNA lesions in cells exposed to methyl methanesulfonate (MMS). We show that MMS induces mtDNA damage in a dose-dependent fashion and that deletion of the APN1 gene enhances the susceptibility of mtDNA to MMS. Repair kinetic experiments demonstrate that in wild-type cells (WT) it takes 4 hr to repair the damage induced by 0.1% MMS, whereas in the apn1Δ strain there is a lag in mtDNA repair that results in significant differences in the repair capacity between the two yeast strains. Analysis of lesions in nuclear DNA (nDNA) after treatment with 0.1% MMS shows a significant difference in the amount of nDNA lesions between WT and apn1Δ cells. Interestingly, comparisons between nDNA and mtDNA damage show that nDNA is more sensitive to the effects of MMS treatment. However, both strains are able to repair the nDNA lesions, contrary to mtDNA repair, which is compromised in the apn1Δ mutant strain. Therefore, although nDNA is more sensitive than mtDNA to the effects of MMS, deletion of APN1 has a stronger phenotype in mtDNA repair than in nDNA. These results highlight the prominent role of APN1 in the repair of environmentally induced mtDNA damage. PMID:19197988

The human mitochondrial single-stranded DNA-binding protein displays distinct kinetics and thermodynamics of DNA binding and exchange

PubMed Central

Qian, Yufeng; Johnson, Kenneth A.

2017-01-01

The human mitochondrial ssDNA-binding protein (mtSSB) is a homotetrameric protein, involved in mtDNA replication and maintenance. Although mtSSB is structurally similar to SSB from Escherichia coli (EcoSSB), it lacks the C-terminal disordered domain, and little is known about the biophysics of mtSSB–ssDNA interactions. Here, we characterized the kinetics and thermodynamics of mtSSB binding to ssDNA by equilibrium titrations and stopped-flow kinetic measurements. We show that the mtSSB tetramer can bind to ssDNA in two distinct binding modes: (SSB)30 and (SSB)60, defined by DNA binding site sizes of 30 and 60 nucleotides, respectively. We found that the binding mode is modulated by magnesium ion and NaCl concentration, but unlike EcoSSB, the mtSSB does not show negative intersubunit cooperativity. Global fitting of both the equilibrium and kinetic data afforded estimates for the rate and equilibrium constants governing the formation of (SSB)60 and (SSB)30 complexes and for the transitions between the two binding modes. We found that the mtSSB tetramer binds to ssDNA with a rate constant near the diffusion limit (2 × 109 m−1 s−1) and that longer DNA (≥60 nucleotides) rapidly wraps around all four monomers, as revealed by FRET assays. We also show that the mtSSB tetramer can directly transfer from one ssDNA molecule to another via an intermediate with two DNA molecules bound to the mtSSB. In conclusion, our results indicate that human mtSSB shares many physicochemical properties with EcoSSB and that the differences may be explained by the lack of an acidic, disordered C-terminal tail in human mtSSB protein. PMID:28615444

Accurate quantitation of circulating cell-free mitochondrial DNA in plasma by droplet digital PCR.

PubMed

Ye, Wei; Tang, Xiaojun; Liu, Chu; Wen, Chaowei; Li, Wei; Lyu, Jianxin

2017-04-01

To establish a method for accurate quantitation of circulating cell-free mitochondrial DNA (ccf-mtDNA) in plasma by droplet digital PCR (ddPCR), we designed a ddPCR method to determine the copy number of ccf-mtDNA by amplifying mitochondrial ND1 (MT-ND1). To evaluate the sensitivity and specificity of the method, a recombinant pMD18-T plasmid containing MT-ND1 sequences and mtDNA-deleted (ρ 0 ) HeLa cells were used, respectively. Subsequently, different plasma samples were prepared for ddPCR to evaluate the feasibility of detecting plasma ccf-mtDNA. In the results, the ddPCR method showed high sensitivity and specificity. When the DNA was extracted from plasma prior to ddPCR, the ccf-mtDNA copy number was higher than that measured without extraction. This difference was not due to a PCR inhibitor, such as EDTA-Na 2 , an anti-coagulant in plasma, because standard EDTA-Na 2 concentration (5 mM) did not significantly inhibit ddPCR reactions. The difference might be attributable to plasma exosomal mtDNA, which was 4.21 ± 0.38 copies/μL of plasma, accounting for ∼19% of plasma ccf-mtDNA. Therefore, ddPCR can quickly and reliably detect ccf-mtDNA from plasma with a prior DNA extraction step, providing for a more accurate detection of ccf-mtDNA. The direct use of plasma as a template in ddPCR is suitable for the detection of exogenous cell-free nucleic acids within plasma, but not of nucleic acids that have a vesicle-associated form, such as exosomal mtDNA. Graphical Abstract Designs of the present work. *: Module 1, #: Module 2, &: Module 3.

A somatic T15091C mutation in the Cytb gene of mouse mitochondrial DNA dominantly induces respiration defects.

PubMed

Hayashi, Chisato; Takibuchi, Gaku; Shimizu, Akinori; Mito, Takayuki; Ishikawa, Kaori; Nakada, Kazuto; Hayashi, Jun-Ichi

2015-08-07

Our previous studies provided evidence that mammalian mitochondrial DNA (mtDNA) mutations that cause mitochondrial respiration defects behave in a recessive manner, because the induction of respiration defects could be prevented with the help of a small proportion (10%-20%) of mtDNA without the mutations. However, subsequent studies found the induction of respiration defects by the accelerated accumulation of a small proportion of mtDNA with various somatic mutations, indicating the presence of mtDNA mutations that behave in a dominant manner. Here, to provide the evidence for the presence of dominant mutations in mtDNA, we used mouse lung carcinoma P29 cells and examined whether some mtDNA molecules possess somatic mutations that dominantly induce respiration defects. Cloning and sequence analysis of 40-48 mtDNA molecules from P29 cells was carried out to screen for somatic mutations in protein-coding genes, because mutations in these genes could dominantly regulate respiration defects by formation of abnormal polypeptides. We found 108 missense mutations existing in one or more of 40-48 mtDNA molecules. Of these missense mutations, a T15091C mutation in the Cytb gene was expected to be pathogenic due to the presence of its orthologous mutation in mtDNA from a patient with cardiomyopathy. After isolation of many subclones from parental P29 cells, we obtained subclones with various proportions of T15091C mtDNA, and showed that the respiration defects were induced in a subclone with only 49% T15091C mtDNA. Because the induction of respiration defects could not be prevented with the help of the remaining 51% mtDNA without the T15091C mutation, the results indicate that the T15091C mutation in mtDNA dominantly induced the respiration defects. Copyright © 2015 Elsevier Inc. All rights reserved.

Resolving the tips of the tree of life: How much mitochondrialdata doe we need?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bonett, Ronald M.; Macey, J. Robert; Boore, Jeffrey L.

2005-04-29

Mitochondrial (mt) DNA sequences are used extensively to reconstruct evolutionary relationships among recently diverged animals,and have constituted the most widely used markers for species- and generic-level relationships for the last decade or more. However, most studies to date have employed relatively small portions of the mt-genome. In contrast, complete mt-genomes primarily have been used to investigate deep divergences, including several studies of the amount of mt sequence necessary to recover ancient relationships. We sequenced and analyzed 24 complete mt-genomes from a group of salamander species exhibiting divergences typical of those in many species-level studies. We present the first comprehensive investigationmore » of the amount of mt sequence data necessary to consistently recover the mt-genome tree at this level, using parsimony and Bayesian methods. Both methods of phylogenetic analysis revealed extremely similar results. A surprising number of well supported, yet conflicting, relationships were found in trees based on fragments less than {approx}2000 nucleotides (nt), typical of the vast majority of the thousands of mt-based studies published to date. Large amounts of data (11,500+ nt) were necessary to consistently recover the whole mt-genome tree. Some relationships consistently were recovered with fragments of all sizes, but many nodes required the majority of the mt-genome to stabilize, particularly those associated with short internal branches. Although moderate amounts of data (2000-3000 nt) were adequate to recover mt-based relationships for which most nodes were congruent with the whole mt-genome tree, many thousands of nucleotides were necessary to resolve rapid bursts of evolution. Recent advances in genomics are making collection of large amounts of sequence data highly feasible, and our results provide the basis for comparative studies of other closely related groups to optimize mt sequence sampling and phylogenetic resolution at the ''tips'' of the Tree of Life.« less

LncRNA MT1JP functions as a ceRNA in regulating FBXW7 through competitively binding to miR-92a-3p in gastric cancer.

PubMed

Zhang, Gang; Li, Shuwei; Lu, Jiafei; Ge, Yuqiu; Wang, Qiaoyan; Ma, Gaoxiang; Zhao, Qinghong; Wu, Dongdong; Gong, Weida; Du, Mulong; Chu, Haiyan; Wang, Meilin; Zhang, Aihua; Zhang, Zhengdong

2018-05-02

Emerging evidence has shown that dysregulation function of long non-coding RNAs (lncRNAs) implicated in gastric cancer (GC). However, the role of the differentially expressed lncRNAs in GC has not fully explained. LncRNA expression profiles were determined by lncRNA microarray in five pairs of normal and GC tissues, further validated in another 75 paired tissues by quantitative real-time PCR (qRT-PCR). Overexpression of lncRNA MT1JP was conducted to assess the effect of MT1JP in vitro and in vivo. The biological functions were demonstrated by luciferase reporter assay, western blotting and rescue experiments. LncRNA MT1JP was significantly lower in GC tissues than adjacent normal tissues, and higher MT1JP was remarkably related to lymph node metastasis and advance stage. Besides, GC patients with higher MT1JP expression had a well survival. Functionally, overexpression of lncRNA MT1JP inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro, and inhibited tumor growth and metastasis in vivo. Functional analysis showed that lncRNA MT1JP regulated FBXW7 expression by competitively binding to miR-92a-3p. MiR-92a-3p and down-regulated FBXW7 reversed cell phenotypes caused by lncRNA MT1JP by rescue analysis. MT1JP, a down-regulated lncRNA in GC, was associated with malignant tumor phenotypes and survival of GC. MT1JP regulated the progression of GC by functioning as a competing endogenous RNA (ceRNA) to competitively bind to miR-92a-3p and regulate FBXW7 expression. Our study provided new insight into the post-transcriptional regulation mechanism of lncRNA MT1JP, and suggested that MT1JP may act as a potential therapeutic target and prognosis biomarker for GC.

Nitrosylation Mechanisms of Mycobacterium tuberculosis and Campylobacter jejuni Truncated Hemoglobins N, O, and P

PubMed Central

Ascenzi, Paolo; di Masi, Alessandra; Tundo, Grazia R.; Pesce, Alessandra; Visca, Paolo; Coletta, Massimo

2014-01-01

Truncated hemoglobins (trHbs) are widely distributed in bacteria and plants and have been found in some unicellular eukaryotes. Phylogenetic analysis based on protein sequences shows that trHbs branch into three groups, designated N (or I), O (or II), and P (or III). Most trHbs are involved in the O2/NO chemistry and/or oxidation/reduction function, permitting the survival of the microorganism in the host. Here, a detailed comparative analysis of kinetics and/or thermodynamics of (i) ferrous Mycobacterium tubertulosis trHbs N and O (Mt-trHbN and Mt-trHbO, respectively), and Campylobacter jejuni trHb (Cj-trHbP) nitrosylation, (ii) nitrite-mediated nitrosylation of ferrous Mt-trHbN, Mt-trHbO, and Cj-trHbP, and (iii) NO-based reductive nitrosylation of ferric Mt-trHbN, Mt-trHbO, and Cj-trHbP is reported. Ferrous and ferric Mt-trHbN and Cj-trHbP display a very high reactivity towards NO; however, the conversion of nitrite to NO is facilitated primarily by ferrous Mt-trHbN. Values of kinetic and/or thermodynamic parameters reflect specific trHb structural features, such as the ligand diffusion pathways to/from the heme, the heme distal pocket structure and polarity, and the ligand stabilization mechanisms. In particular, the high reactivity of Mt-trHbN and Cj-trHbP reflects the great ligand accessibility to the heme center by two protein matrix tunnels and the E7-path, respectively, and the penta-coordination of the heme-Fe atom. In contrast, the heme-Fe atom of Mt-trHbO the ligand accessibility to the heme center of Mt-trHbO needs large conformational readjustments, thus limiting the heme-based reactivity. These results agree with different roles of Mt-trHbN, Mt-trHbO, and Cj-trHbP in vivo. PMID:25051055

Cadium pathways during gestation and lactation in control vs. metallothionein 1,2-knockout mice.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brako, E. E.; Wilson, A. K.; Jonah, M. M.

2003-01-01

Effects of metallothionein (MT) on cadmium absorption and transfer pathways during gestation and lactation in mice were investigated. Female 129/SvJ metallothionein-knockout (MT1,2KO) and metallothionein-normal (MTN) mice received drinking water containing trace amounts of {sup 109}CdCl{sub 2} (0.15 ng Cd/ml; 0.074 {mu}Ci {sup 109}Cd/ml). {sup 109}Cd and MT in maternal, fetal, and pup tissues were measured on gestation days 7, 14, and 17 and lactation day 11. In dams, MT influenced both the amount of {sup 109}Cd transferred from intestine into body (two- to three-fold higher in MT1,2KO than MTN dams) and tissue-specific {sup 109}Cd distribution (higher liver/kidney ratio in MT1,2KOmore » dams). Placental {sup 109}Cd concentrations in MT1,2KO dams were three- and seven-fold higher on gestation days 14 and 17, respectively, than in MTN dams. Fetal {sup 109}Cd levels were low in both mouse types, but at least 10-fold lower in MTN fetuses. MT had no effect on the amount of {sup 109}Cd transferred to pups via milk; furthermore, 85--90% of total pup {sup 109}Cd was recovered in gastrointestinal tracts of both types, despite high duodenal MT only in MTN pups. A relatively large percentage of milk-derived intestinal {sup 109}Cd was transferred to other pup tissues in both MT1,2KO and MTN pups (14 and 10%, respectively). These results demonstrate that specific sequestration of cadmium by both maternal and neonatal intestinal tract does not require MT. Although MT decreased oral cadmium transfer from intestine to body tissues at low cadmium exposure levels, MT did not play a major role in restricting transfer of cadmium from dam to fetus via placenta and to neonate via milk.« less

Effects of environmental salinity and 17alpha-methyltestosterone on growth and oxygen consumption in the tilapia, Oreochromis mossambicus.

PubMed

Sparks, Russell T; Shepherd, Brian S; Ron, Benny; Harold Richman, N; Riley, Larry G; Iwama, George K; Hirano, Tetsuya; Gordon Grau, E

2003-12-01

Effects of environmental salinity and 17alpha-methyltestosterone (MT) on growth and oxygen consumption were examined in the tilapia, Oreochromis mossambicus. Yolk-sac fry were collected from brood stock in fresh water (FW). After yolk-sac absorption, they were assigned randomly to one of four groups: FW, MT treatment in FW, seawater (SW) and MT treatment in SW. All treatment groups were fed to satiation three times daily. The fish reared in SW (both control and MT-treated groups) grew significantly larger than either group in FW from day 43 throughout the experiment (195 days). The fish fed with MT added to their feed grew significantly larger than their respective controls from day 85 in FW and in SW until the end of the experiment. The routine metabolic rate (RMR) was determined monthly from month 2 (day 62) to month 5 (day 155). A significant negative correlation was seen between RMR and body mass in all treatment groups. Among fish of the same age, the SW-reared tilapia had significantly lower RMRs than the FW-reared fish. The MT-treated fish in SW showed significantly lower RMRs than the SW control group at months 3-5, whereas MT treatment in FW significantly increased the RMR at month 3. Comparison of regression lines between RMR and body mass indicates that MT treatment in FW caused a significant increase in oxygen consumption at a given mass of the fish, whereas MT treatment was without effect on RMR in SW-reared fish. These results clearly indicate that SW-rearing and MT treatment accelerate growth of tilapia, and that RMR decreases as fish size increased. It is also likely that the increased RMR and growth in MT-treated tilapia in FW may be due to the metabolic actions of MT, although the reason for the absence of MT treatment in SW is unclear.

Protective effects of melatonin on ischemia-reperfusion induced myocardial damage and hemodynamic recovery in rats.

PubMed

Liu, L-F; Qin, Q; Qian, Z-H; Shi, M; Deng, Q-C; Zhu, W-P; Zhang, H; Tao, X-M; Liu, Y

2014-01-01

To investigate the mechanism of melatonin (MT) protection of adult rate myocardial ischemia-reperfusion injury and its influence on rat's hemodynamic recovery. 48 rats were randomly divided into MT group (n=36) and the control group (n=12), MT group was divided into three sub-groups according to different dosages: Group I (n=12) was administered with 2.5 mg/kg MT; Group II (n=12) was administered with 5 mg/kg MT; Group III (n=12) was administered with 10 mg/kg MT. The electrocardiogram of four groups was observed with the left coronary artery blocked for 10min at first and then reperfused for 15min. Hemodynamic evolving was observed and changes in energy metabolism of rat myocardium were monitored. TUNEL and immunohistochemistry were applied to detect the cell apoptosis index, protein expression of Bcl-2 and Bax. LVDP (left ventricular developed pressure) and ± dp/dt in MT group presented better recovery at various time points than the control group. Among them, Group III had the optimal recovery degree (p < 0.05). After MT administration, ATP content in myocardial cells in MT group was significantly higher than the control group. Compared with the control group, the concentration of mitochondrial MDA and Ca2+ in myocardial cells in MT group showed a downward trend. But its GSH concentration was significantly higher than the control group (p < 0.05). The improvement degree of ATP, MDA, GSH and Ca2+ concentration in Group II over-performed Group I (p < 0.05). MT-intervened myocardial apoptosis index (AI) and Bax positive expression index declined while Bcl-2 positive expression index increased (p < 0.01). MT effectively inhibited myocardial apoptosis during the myocardial ischemia-reperfusion of rats, protected the structural integrity of mitochondria in myocardial cells, promoted ATP synthesis, and avoided heart damage in many ways. This protection mechanism was related with anti-oxidative damage. Meanwhile, MT could promote the hemodynamic recovery after myocardial ischemia-reperfusion in rats.

Characterization of the rubber tree metallothionein family reveals a role in mitigating the effects of reactive oxygen species associated with physiological stress.

PubMed

Huang, Yacheng; Fang, Yongjun; Long, Xiangyu; Liu, Linya; Wang, Jia; Zhu, Jinheng; Ma, Yanyan; Qin, Yunxia; Qi, Jiyan; Hu, Xinwen; Tang, Chaorong

2018-06-01

Metallothioneins (MTs) as reactive oxygen species (ROS) scavengers play important roles in stress response and heavy metal homeostasis. In Hevea brasiliensis (the para rubber tree that is the source of commercial natural rubber) and in other trees, the functions of MTs are not well understood. Latex exudes when the rubber tree is tapped. The flow of latex and its regeneration can be enhanced by tapping, wounding and ethylene treatment, all of which produce ROS as a by-product. Here, we show the presence of four MT genes in H. brasiliensis, comprising three Type 2 (HbMT2, -2a and -2b) and one Type 3 (HbMT3L) isoforms, representing one of the smallest MT gene families among angiosperms. The four HbMTs exhibited distinct tissue expression patterns: HbMT2 and HbMT3L mainly in leaves, HbMT2a specifically in flowers and HbMT2b in diverse tissues. The expression of HbMT2b, an isoform present in latex, decreased significantly in the latex following the stress-inducing treatments of tapping, wounding and ethephon (an ethylene generator). The expressions of the leaf-abundant isoforms, HbMT2 and -3L were up-regulated following pathogenic fungus infection and high-temperature stress, but down-regulated by low-temperature stress. These reactions were consistent with multiple defense- and hormone-responsive cis-acting elements in the HbMT promoters. Nine transcription factors were shown to implicate in the high-temperature responsiveness of HbMT2 and -3L in leaves. Overexpression of HbMT2 in Escherichia coli enhanced the bacterium's tolerance to heavy metals and ROS, consistent with its predicted role as an ROS scavenger. Taken together, our results, along with other relevant studies, suggest an important role of HbMTs in latex regeneration as well as species adaptation via the regulation of ROS homeostasis.

Conference Proceedings from the Annual Carnegie Cognition Symposium (10th) Held at Vail, Colorado on June 2-8, 1974: Cognition and Instruction

DTIC Science & Technology

1976-05-15

the analysis tells us about the data . Analysis of Process Independence Univariate analyses of variance were carried out on the two measures for...Atkinson’s data on third-level optimization is extremely interesting. In a cu.mt controversy about ways to increase equality of educational oPP^tumty Sesame...University Effective Data : 1 May, 1973 Expiration Data : 31 Oct., 1974 Amount of Contract: $30,699 Principal Inveatlgator: Dr. David Klahr («12) 621

One hundred years of earthquake recording at the University of California

USGS Publications Warehouse

Bolt, B. A.

1987-01-01

The best seismographs then available arrived from England in 1887 and were installed at Lick Observatory on Mt.Hamilton and at the Students Astronomical Observatory on the Berkeley campus. The first California earthquake recorded by the Lick instrument was on April 24, 1887. These seismographic stations have functioned continuously from their founding to the present day, with improvements in instruments from time to time as technology advanced. Now they are part of a sesimogrpahic network of 16 stations recording with great completeness both local and distant earthquakes. 

The Effect of Enhanced Diabatic Heating on Stratospheric Circulation. Degree awarded by Michigan University, 1997.

NASA Technical Reports Server (NTRS)

Kleb, Mary M.

1997-01-01

The objective of this research focuses on the stratospheric dynamical response to the increase in aerosol loading and subsequent enhanced diabatic heating resulting from the eruption of Mt. Pinatubo. The Langley research Center three dimensional general circulation model and modifications made to that model for this study are described (addition of hydrogen fluoride tracer and diabatic heating enhancement). Unperturbed hydrogen fluoride distribution is compared to the hydrogen fluoride distribution measured by HALOE. A comparison of control and perturbed model runs is presented.

C. elegans epidermal wounding induces a mitochondrial ROS burst that promotes wound repair

PubMed Central

Xu, Suhong; Chisholm, Andrew D.

2014-01-01

SUMMARY Reactive oxygen species (ROS) such as hydrogen peroxide are generated at wound sites and act as long-range signals in wound healing. The roles of other ROS in wound repair are little explored. Here we reveal a cytoprotective role for mitochondrial ROS (mtROS) in C. elegans skin wound healing. We show that skin wounding causes local production of mtROS superoxide at the wound site. Inhibition of mtROS levels by mitochondrial superoxide-specific antioxidants blocks actin-based wound closure, whereas elevation of mtROS promotes wound closure and enhances survival of mutant animals defective in wound healing. mtROS act downstream of wound-triggered Ca2+ influx. We find that the Mitochondrial Calcium Uniporter MCU-1 is essential for rapid mitochondrial Ca2+ uptake and mtROS production after wounding. mtROS can promote wound closure by local inhibition of Rho GTPase activity via a redox-sensitive motif. These findings delineate a pathway acting via mtROS that promotes cytoskeletal responses in wound healing. PMID:25313960

Defects in Mitochondrial DNA Replication and Human Disease

PubMed Central

Copeland, William C.

2011-01-01

Mitochondrial DNA (mtDNA) is replicated by the DNA polymerase γ in concert with accessory proteins such as the mitochondrial DNA helicase, single stranded DNA binding protein, topoisomerase, and initiating factors. Nucleotide precursors for mtDNA replication arise from the mitochondrial salvage pathway originating from transport of nucleosides, or alternatively from cytoplasmic reduction of ribonucleotides. Defects in mtDNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mtDNA deletions, point mutations, or depletion which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mtDNA depletion syndromes (MDS) such as Alpers or early infantile hepatocerebral syndromes, and mtDNA deletion disorders, such as progressive external ophthalmoplegia (PEO), ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). This review focuses on our current knowledge of genetic defects of mtDNA replication (POLG, POLG2, C10orf2) and nucleotide metabolism (TYMP, TK2, DGOUK, and RRM2B) that cause instability of mtDNA and mitochondrial disease. PMID:22176657

Mindfulness training and stress reactivity in substance abuse: results from a randomized, controlled stage I pilot study.

PubMed

Brewer, Judson A; Sinha, Rajita; Chen, Justin A; Michalsen, Ravenna N; Babuscio, Theresa A; Nich, Charla; Grier, Aleesha; Bergquist, Keri L; Reis, Deidre L; Potenza, Marc N; Carroll, Kathleen M; Rounsaville, Bruce J

2009-01-01

Stress is important in substance use disorders (SUDs). Mindfulness training (MT) has shown promise for stress-related maladies. No studies have compared MT to empirically validated treatments for SUDs. The goals of this study were to assess MT compared to cognitive behavioral therapy (CBT) in substance use and treatment acceptability, and specificity of MT compared to CBT in targeting stress reactivity. Thirty-six individuals with alcohol and/or cocaine use disorders were randomly assigned to receive group MT or CBT in an outpatient setting. Drug use was assessed weekly. After treatment, responses to personalized stress provocation were measured. Fourteen individuals completed treatment. There were no differences in treatment satisfaction or drug use between groups. The laboratory paradigm suggested reduced psychological and physiological indices of stress during provocation in MT compared to CBT. This pilot study provides evidence of the feasibility of MT in treating SUDs and suggests that MT may be efficacious in targeting stress.

Animal Mitochondrial DNA Replication

PubMed Central

Ciesielski, Grzegorz L.; Oliveira, Marcos T.; Kaguni, Laurie S.

2016-01-01

Recent advances in the field of mitochondrial DNA (mtDNA) replication highlight the diversity of both the mechanisms utilized and the structural and functional organization of the proteins at mtDNA replication fork, despite the simplicity of the animal mtDNA genome. DNA polymerase γ, mtDNA helicase and mitochondrial single-stranded DNA-binding protein- the key replisome proteins, have evolved distinct structural features and biochemical properties. These appear to be correlated with mtDNA genomic features in different metazoan taxa and with their modes of DNA replication, although a substantial integrative research is warranted to establish firmly these links. To date, several modes of mtDNA replication have been described for animals: rolling circle, theta, strand-displacement, and RITOLS/bootlace. Resolution of a continuing controversy relevant to mtDNA replication in mammals/vertebrates will have a direct impact on the mechanistic interpretation of mtDNA-related human diseases. Here we review these subjects, integrating earlier and recent data to provide a perspective on the major challenges for future research. PMID:27241933

MT1 and MT2 Melatonin Receptors: A Therapeutic Perspective

PubMed Central

Liu, Jiabei; Clough, Shannon J.; Hutchinson, Anthony J.; Adamah-Biassi, Ekue B.; Popovska-Gorevski, Marina; Dubocovich, Margarita L.

2016-01-01

Melatonin, or 5-methoxy-N-acetyltryptamine, is synthesized and released by the pineal gland and locally in the retina following a circadian rhythm, with low levels during the day and elevated levels at night. Melatonin activates two high-affinity G protein–coupled receptors, termed MT1 and MT2, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer. Progress in understanding the role of melatonin receptors in the modulation of sleep and circadian rhythms has led to the discovery of a novel class of melatonin agonists for treating insomnia, circadian rhythms, mood disorders, and cancer. This review describes the pharmacological properties of a slow-release melatonin preparation (i.e., Circadin®) and synthetic ligands (i.e., agomelatine, ramelteon, tasimelteon), with emphasis on identifying specific therapeutic effects mediated through MT1 and MT2 receptor activation. Discovery of selective ligands targeting the MT1 or the MT2 melatonin receptors may promote the development of novel and more efficacious therapeutic agents. PMID:26514204

Japanese Alzheimer's Disease and Other Complex Disorders Diagnosis Based on Mitochondrial SNP Haplogroups

PubMed Central

Takasaki, Shigeru

2012-01-01

This paper first explains how the relations between Japanese Alzheimer's disease (AD) patients and their mitochondrial SNP frequencies at individual mtDNA positions examined using the radial basis function (RBF) network and a method based on RBF network predictions and that Japanese AD patients are associated with the haplogroups G2a and N9b1. It then describes a method for the initial diagnosis of Alzheimer's disease that is based on the mtSNP haplogroups of the AD patients. The method examines the relations between someone's mtDNA mutations and the mtSNPs of AD patients. As the mtSNP haplogroups thus obtained indicate which nucleotides of mtDNA loci are changed in the Alzheimer's patients, a person's probability of becoming an AD patient can be predicted by comparing those mtDNA mutations with that person's mtDNA mutations. The proposed method can also be used to diagnose diseases such as Parkinson's disease and type 2 diabetes and to identify people likely to become centenarians. PMID:22848858

Matrine- and oxymatrine-imprinted monodisperse polymers prepared by precipitation polymerization and their applications for the selective extraction of matrine-type alkaloids from Sophora flavescens Aiton.

PubMed

Funaya, Noriko; Haginaka, Jun

2012-07-27

Matrine (MT)- and oxymatrine (OMT)-imprinted monodisperse polymers have been prepared by precipitation polymerization. The prepared molecularly imprinted polymers (MIPs) for MT and OMT, MIP(MT) and MIP(OMT), were monodispersed microspheres of 3.3 and 3.9 μm in diameter, respectively. Binding experiments and Scatchard analyses revealed that two classes of binding sites were formed on MIP(MT) and MIP(OMT). In addition to shape recognition, ionic and hydrophobic interactions seemed to affect the retention and recognition of MT and OMT on MIP(MT) and MIP(OMT), respectively, in low acetonitrile content, and ionic and hydrophilic interactions affected these properties in high acetonitrile content. MIP(MT) was used to selectively extract MT and sophocarpine (13,14-dehydromatrine) from Sophora flavescens root, while MIP(OMT) was used to extract OMT and oxysophocarpine (13,14-dehydrooxymatrine). Copyright © 2012 Elsevier B.V. All rights reserved.

Mindfulness Training and Stress Reactivity in Substance Abuse: Results from A Randomized, Controlled Stage I Pilot Study

PubMed Central

Brewer, Judson A.; Sinha, Rajita; Chen, Justin A.; Michalsen, Ravenna N.; Babuscio, Theresa A.; Nich, Charla; Grier, Aleesha; Bergquist, Keri L.; Reis, Deidre L.; Potenza, Marc N.; Carroll, Kathleen M.; Rounsaville, Bruce J.

2011-01-01

Background Stress is important in substance use disorders (SUDs). Mindfulness training (MT) has shown promise for stress-related maladies. No studies have compared MT to empirically-validated treatments for SUDs. Goals to assess MT compared to cognitive behavioral therapy (CBT) in substance use and treatment acceptability, and specificity of MT compared to CBT in targeting stress reactivity. Methods 36 individuals with alcohol and/or cocaine use disorders were randomly assigned to receive group MT or CBT in an outpatient setting. Drug use was assessed weekly. After treatment, responses to personalized stress provocation were measured. Results Fourteen individuals completed treatment. There were no differences in treatment satisfaction, or drug use between groups. The laboratory paradigm suggested reduced psychological and physiological indices of stress during provocation in MT compared to CBT. Conclusions This pilot study provides evidence of the feasibility of MT in treating SUDs and suggests that MT may be efficacious in targeting stress. PMID:19904666

Cigarette smoking and hOGG1 Ser326Cys polymorphism are associated with 8-OHdG accumulation on mitochondrial DNA in thoracic esophageal squamous cell carcinoma.

PubMed

Lin, Chen-Sung; Wang, Liang-Shun; Chou, Teh-Ying; Hsu, Wen-Hu; Lin, Hui-Chen; Lee, Shu-Yu; Lee, Mau-Hua; Chang, Shi-Chuan; Wei, Yau-Huei

2013-12-01

We examined whether cigarette smoking affects the degrees of oxidative damage (8-hydroxyl-2'-deoxyguanosine [8-OHdG]) on mitochondrial DNA (mtDNA), whether the degree of 8-OHdG accumulation on mtDNA is related to the increased total mtDNA copy number, and whether human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphisms affect the degrees of 8-OHdG accumulation on mtDNA in thoracic esophageal squamous cell carcinoma (TESCC). DNA extracted from microdissected tissues of paired noncancerous esophageal muscles, noncancerous esophageal mucosa, and cancerous TESCC nests (n = 74) along with metastatic lymph nodes (n = 38) of 74 TESCC patients was analyzed. Both the mtDNA copy number and mtDNA integrity were analyzed by quantitative real-time polymerase chain reaction (PCR). The hOGG1 Ser326Cys polymorphisms were identified by restriction fragment length polymorphism PCR and PCR-based direct sequencing. Among noncancerous esophageal mucosa, cancerous TESCC nests, and metastatic lymph nodes, the mtDNA integrity decreased (95.2 to 47.9 to 18.6 %; P < 0.001) and the mtDNA copy number disproportionally increased (0.163 to 0.204 to 0.207; P = 0.026). In TESCC, higher indexes of cigarette smoking (0, 0-20, 20-40, and >40 pack-years) were related to an advanced pathologic N category (P = 0.038), elevated mtDNA copy number (P = 0.013), higher mtDNA copy ratio (P = 0.028), and increased mtDNA integrity (P = 0.069). The TESCC mtDNA integrity in patients with Ser/Ser, Ser/Cys, and Cys/Cys hOGG1 variants decreased stepwise from 65.2 to 52.1 to 41.3 % (P = 0.051). Elevated 8-OHdG accumulations on mtDNA in TESCC were observed. Such accumulations were associated with a compensatory increase in total mtDNA copy number, indexes of cigarette smoking, and hOGG1 Ser326Cys polymorphisms.

The Impact of Music Therapy on Anxiety in Cancer Patients Undergoing Simulation for Radiation Therapy.

PubMed

Rossetti, Andrew; Chadha, Manjeet; Torres, B Nelson; Lee, Jae K; Hylton, Donald; Loewy, Joanne V; Harrison, Louis B

2017-09-01

Radiation therapy (RT) is associated with high stress levels. The role of music therapy (MT) for patients receiving RT is not well described. This study evaluates the impact of MT on anxiety and distress during simulation in patients with newly diagnosed head and neck or breast cancer. This institutional review board-approved randomized trial of MT versus no MT at the time of simulation included the pre-State-Trait Anxiety Inventory (STAI-S Anxiety) questionnaire and Symptom Distress Thermometer (SDT). Patients randomized to MT received a consultation with a music therapist, during which music of the patients' choice to be played during simulation was selected. The no-MT patients did not receive the MT consultation, nor did they hear prerecorded music during simulation. Subsequent to the simulation, all patients repeated the STAI-S Anxiety questionnaire and the SDT. Of the 78 patients enrolled (39 in MT group and 39 in no-MT group), 38 had breast cancer and 40 had head and neck cancer. The male-female ratio was 27:51. The overall mean pre- and post-simulation STAI-S scores were 38.7 (range, 20-60) and 35.2 (range, 20-72), respectively. The overall mean pre- and post-simulation SDT scores were 3.2 (range, 0-10) and 2.5 (range, 0-10), respectively. The MT group had mean pre- and post-simulation STAI-S scores of 39.1 and 31.0, respectively (P<.0001), and the mean SDT scores before and after simulation were 3.2 and 1.7, respectively (P<.0001). The no-MT group's mean pre- and post-simulation STAI-S scores were 38.3 and 39.5, respectively (P=.46), and the mean SDT scores were 3 and 3.2, respectively (P=.51). MT significantly lowered patient anxiety and distress during the simulation procedure on the basis of the STAI-S questionnaire and SDT. Incorporating culturally centered individualized MT may be an effective intervention to reduce stressors. Continued research defining the role of MT intervention in improving the patient experience by reducing anxiety is warranted. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Multiple essential MT1-MMP functions in tooth root formation, dentinogenesis, and tooth eruption

PubMed Central

Wimer, H.F.; Yamada, S.S.; Yang, T.; Holmbeck, K.; Foster, B.L.

2016-01-01

Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a transmembrane zinc-endopeptidase that breaks down extracellular matrix components, including several collagens, during tissue development and physiological remodeling. MT1-MMP-deficient mice (MT1-MMP−/−) feature severe defects in connective tissues, such as impaired growth, osteopenia, fibrosis, and conspicuous loss of molar tooth eruption and root formation. In order to define the functions of MT1-MMP during root formation and tooth eruption, we analyzed the development of teeth and surrounding tissues in the absence of MT1-MMP. In situ hybridization showed that MT1-MMP was widely expressed in cells associated with teeth and surrounding connective tissues during development. Multiple defects in dentoalveolar tissues were associated with loss of MT1-MMP. Root formation was inhibited by defective structure and function of Hertwig's epithelial root sheath (HERS). However, no defect was found in creation of the eruption pathway, suggesting that tooth eruption was hampered by lack of alveolar bone modeling/remodeling coincident with reduced periodontal ligament (PDL) formation and integration with the alveolar bone. Additionally, we identified a significant defect in dentin formation and mineralization associated with the loss of MT1-MMP. To segregate these multiple defects and trace their cellular origin, conditional ablation of MT1-MMP was performed in epithelia and mesenchyme. Mice featuring selective loss of MT1-MMP activity in the epithelium were indistinguishable from wild type mice, and importantly, featured a normal HERS structure and molar eruption. In contrast, selective knock-out of MT1-MMP in Osterix-expressing mesenchymal cells, including osteoblasts and odontoblasts, recapitulated major defects from the global knock-out including altered HERS structure, short roots, defective dentin formation and mineralization, and reduced alveolar bone formation, although molars were able to erupt. These data indicate that MT1-MMP activity in the dental mesenchyme, and not in epithelial-derived HERS, is essential for proper tooth root formation and eruption. In summary, our studies point to an indispensable role for MT1-MMP-mediated matrix remodeling in tooth eruption through effects on bone formation, soft tissue remodeling and organization of the follicle/PDL region. PMID:26780723

Aconitase couples metabolic regulation to mitochondrial DNA maintenance.

PubMed

Chen, Xin Jie; Wang, Xiaowen; Kaufman, Brett A; Butow, Ronald A

2005-02-04

Mitochondrial DNA (mtDNA) is essential for cells to maintain respiratory competency and is inherited as a protein-DNA complex called the nucleoid. We have identified 22 mtDNA-associated proteins in yeast, among which is mitochondrial aconitase (Aco1p). We show that this Krebs-cycle enzyme is essential for mtDNA maintenance independent of its catalytic activity. Regulation of ACO1 expression by the HAP and retrograde metabolic signaling pathways directly affects mtDNA maintenance. When constitutively expressed, Aco1p can replace the mtDNA packaging function of the high-mobility-group protein Abf2p. Thus, Aco1p may integrate metabolic signals and mtDNA maintenance.

The influence of biological and environmental factors on metallothionein concentration in the blood.

PubMed

Kowalska, Katarzyna; Bizoń, Anna; Zalewska, Marta; Milnerowicz, Halina

2015-01-01

The concentration of metallothionein (MT), a low-molecular-weight protein, is regulated by many factors, primarily metals (zinc, cadmium, copper), cytokines, glucocorticoides and free radicals. These factors are determined by such aspects of human biology as gender, pregnancy and age, as well as by environmental factors including the use of oral contraceptives and cigarette smoking, all which may affect MT levels in the body. The aim of this study was to investigate the influence of these biological and environmental factors on MT concentrations in erythrocyte lysate and in plasma. MT concentrations were determined by a two-step direct enzyme-linked immunosorbent assay. Evaluation of exposure to cigarette smoking was performed by checking cotinine levels in the plasma of subjects. The studies showed higher MT concentrations in both the erythrocyte lysate and plasma of women when compared to men. Furthermore, pregnancy causes an increase of MT concentration in plasma, while oral contraceptives cause an elevated concentration of MT in erythrocyte lysate. Age impacts plasma MT concentrations in men, whereas it does not affect concentrations of MT in erythrocyte lysate. Copyright © 2014 Elsevier GmbH. All rights reserved.

Quorum Sensing Extracellular Death Peptides Enhance the Endoribonucleolytic Activities of Mycobacterium tuberculosis MazF Toxins

PubMed Central

Nigam, Akanksha; Kumar, Sathish

2018-01-01

ABSTRACT mazEF is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. Previously, we characterized several quorum sensing peptides called "extracellular death factors" (EDFs). When secreted from bacterial cultures, EDFs induce interspecies cell death. EDFs also enhance the endoribonucleolytic activity of Escherichia coli MazF. Mycobacterium tuberculosis carries several mazEF modules. Among them, the endoribonucleolytic activities of MazF proteins mt-1, mt-3, and mt-6 were identified. MazF-mt6 and MazF-mt-3 cleave M. tuberculosis rRNAs. Here we report the in vitro effects of EDFs on the endoribonucleolytic activities of M. tuberculosis MazFs. Escherichia coli EDF (EcEDF) and the three Pseudomonas aeruginosa EDFs (PaEDFs) individually enhance the endoribonucleolytic activities of MazF-mt6 and MazF-mt3 and overcome the inhibitory effect of MazE-mt3 or MazE-mt6 on the endoribonucleolytic activities of the respective toxins. We propose that these EDFs can serve as a basis for a novel class of antibiotics against M. tuberculosis. PMID:29717013

Associations of mitochondrial haplogroups and mitochondrial DNA copy numbers with end-stage renal disease in a Han population.

PubMed

Zhang, Yuheng; Zhao, Ying; Wen, Shuzhen; Yan, Rengna; Yang, Qinglan; Chen, Huimei

2017-09-01

Mitochondrial DNA (mtDNA) is closely related to mitochondrion function, and variations have been suggested to be involved in pathogenesis of complex diseases. The present study sought to elucidate mitochondrial haplogroups and mtDNA copy number in end-stage renal disease (ESRD) in a Han population. First, the mitochondrial haplogroups of 37 ESRD patients were clustered into several haplogroups, and haplogroup A & D were taken as the candidate risk haplogroups for ESRD. Second, the frequencies of A and D were assessed in 344 ESRD patients and 438 healthy controls, respectively. Haplogroup D was found to be risk maker for ESRD in young subjects (<30 years) with an OR of 2.274. Finally, intracellular and cell-free mtDNA copy numbers were evaluated with quantitative-PCR. The ESRD patients exhibited greater cell-free mtDNA contents than the healthy controls but less intracellular mtDNA. Haplogroup D exhibited a further increase in cell-free mtDNA content and a decrease in intracellular mtDNA content among the ESRDs patients. Our findings suggest that mtNDA haplogroup D may contributes to pathogenesis of early-onset ESRD through alterations of mtDNA copy numbers.

Mitochondrial DNA Damage and its Consequences for Mitochondrial Gene Expression

PubMed Central

Cline, Susan D.

2012-01-01

How mitochondria process DNA damage and whether a change in the steady-state level of mitochondrial DNA damage (mtDNA) contributes to mitochondrial dysfunction are questions that fuel burgeoning areas of research into aging and disease pathogenesis. Over the past decade, researchers have identified and measured various forms of endogenous and environmental mtDNA damage and have elucidated mtDNA repair pathways. Interestingly, mitochondria do not appear to contain the full range of DNA repair mechanisms that operate in the nucleus, although mtDNA contains types of damage that are targets of each nuclear DNA repair pathway. The reduced repair capacity may, in part, explain the high mutation frequency of the mitochondrial chromosome. Since mtDNA replication is dependent on transcription, mtDNA damage may alter mitochondrial gene expression at three levels: by causing DNA polymerase γ nucleotide incorporation errors leading to mutations, by interfering with the priming of mtDNA replication by the mitochondrial RNA polymerase, or by inducing transcriptional mutagenesis or premature transcript termination. This review summarizes our current knowledge of mtDNA damage, its repair, and its effects on mtDNA integrity and gene expression. PMID:22728831

TOP1MT deficiency promotes GC invasion and migration via the enhancements of LDHA expression and aerobic glycolysis.

PubMed

Wang, Hongqiang; Zhou, Rui; Sun, Li; Xia, Jianling; Yang, Xuchun; Pan, Changqie; Huang, Na; Shi, Min; Bin, Jianping; Liao, Yulin; Liao, Wangjun

2017-11-01

Aerobic glycolysis plays an important role in cancer progression. New target genes regulating cancer aerobic glycolysis must be explored to improve patient prognosis. Mitochondrial topoisomerase I ( TOP1MT ) deficiency suppresses glucose oxidative metabolism but enhances glycolysis in normal cells. Here, we examined the role of TOP1MT in gastric cancer (GC) and attempted to determine the underlying mechanism. Using in vitro and in vivo experiments and analyzing the clinicopathological characteristics of patients with GC, we found that TOP1MT expression was lower in GC samples than in adjacent nonmalignant tissues. TOP1MT knockdown significantly promoted GC migration and invasion in vitro and in vivo Importantly, TOP1MT silencing increased glucose consumption, lactate production, glucose transporter 1 expression and the epithelial-mesenchymal transition (EMT) in GC. Additionally, regulation of glucose metabolism induced by TOP1MT was significantly associated with lactate dehydrogenase A (LDHA) expression. A retrospective analysis of clinical data from 295 patients with GC demonstrated that low TOP1MT expression was associated with lymph node metastasis, recurrence and high mortality rates. TOP1MT deficiency enhanced glucose aerobic glycolysis by stimulating LDHA to promote GC progression. © 2017 The authors.

Microbial translocation and skeletal muscle in young and old vervet monkeys.

PubMed

Kavanagh, Kylie; Brown, Richelle N; Davis, Ashley T; Uberseder, Beth; Floyd, Edison; Pfisterer, Bianca; Shively, Carol A

2016-06-01

Intestinal barrier dysfunction leads to microbial translocation (MT) and inflammation in vertebrate and invertebrate animal models. Age is recently recognized as a factor leading to MT, and in some human and animal model studies, MT was associated with physical function. We evaluated sarcopenia, inflammation, MT biomarkers, and muscle insulin sensitivity in healthy female vervet monkeys (6-27 years old). Monkeys were fed consistent diets and had large and varied environments to facilitate physical activity, and stable social conditions. Aging led to sarcopenia as indicated by reduced walking speeds and muscle mass, but general metabolic health was similar in older monkeys (n = 25) as compared to younger ones (n = 26). When older monkeys were physically active, their MT burden approximated that in young monkeys; however, when older monkeys were sedentary, MT burden was dramatically increased. MT levels were positively associated with inflammatory burden and negatively associated with skeletal muscle insulin sensitivity. Time spent being active was positively associated with insulin sensitivity as expected, but this relationship was specifically modified by the individual monkey's MT, not inflammatory burden. Our data supports clinical observations that MT interacts with physical function as a factor in healthy aging.

Adolescents with greater mental toughness show higher sleep efficiency, more deep sleep and fewer awakenings after sleep onset.

PubMed

Brand, Serge; Gerber, Markus; Kalak, Nadeem; Kirov, Roumen; Lemola, Sakari; Clough, Peter J; Pühse, Uwe; Holsboer-Trachsler, Edith

2014-01-01

Mental toughness (MT) is understood as the display of confidence, commitment, challenge, and control. Mental toughness is associated with resilience against stress. However, research has not yet focused on the relation between MT and objective sleep. The aim of the present study was therefore to explore the extent to which greater MT is associated with objectively assessed sleep among adolescents. A total of 92 adolescents (35% females; mean age, 18.92 years) completed the Mental Toughness Questionnaire. Participants were split into groups of high and low mental toughness. Objective sleep was recorded via sleep electroencephalograms and subjective sleep was assessed via a questionnaire. Compared with participants with low MT, participants with high MT had higher sleep efficiency, a lower number of awakenings after sleep onset, less light sleep, and more deep sleep. They also reported lower daytime sleepiness. Adolescents reporting higher MT also had objectively better sleep, as recorded via sleep electroencephalograms. A bidirectional association between MT and sleep seems likely; therefore, among adolescence, improving sleep should increase MT, and improving MT should increase sleep. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Digital Communications Terminal High Order Programming Language Study (DCT HOL Study). Volume I.

DTIC Science & Technology

1980-11-26

3-3 PASCAL/M Digital Marketing ......... 3-3 PASCAL/MT MT MicroSystems .................... 3-3 PASCAL/Z Ithaca IntersysteMs...II Avocet Systems, Inc. 3.6 PASCAL - ISO PASCAL Whitesmith, Ltd. - PASCAL 64000 lbwlett-Packard - PASCAL/H Digital Marketing - PASCAL/MT MT

44 CFR 15.4 - Inspection.

Code of Federal Regulations, 2013 CFR

2013-10-01

... GENERAL CONDUCT AT THE MT. WEATHER EMERGENCY ASSISTANCE CENTER AND AT THE NATIONAL EMERGENCY TRAINING... containers being brought into, while on or being removed from Mt. Weather or the NETC are subject to... may accompany an arrest. (b) Inspection at Mt. Weather. We authorize inspection at Mt. Weather to...