The Geography of the Beatles Approaching Concepts of Human Geography

ERIC Educational Resources Information Center

Kruse, Robert J., II

2004-01-01

Human geography can be taught by focusing on popular culture contexts with which undergraduate students may already be familiar such as rock music. The Geography of the Beatles introduced undergraduate students to concepts of "new" cultural geography such as space, place, representation, geopolitics, social space, and tourism-pilgrimage…

Using Cocoa and Chocolate to Teach Human Geography

ERIC Educational Resources Information Center

Alberts, Heike C.

2010-01-01

Food topics are uniquely suited to increase students' interest in human geography. A highly processed food like chocolate can be studied in a variety of different ways, making it possible to include chocolate examples and activities at various points in a human geography class. The goals of this article are to provide sufficient background…

A Critical Approach to Discipline of Human Geography as an Apparatus for State Hegemony in Turkey

ERIC Educational Resources Information Center

Özgen, Nurettin

2016-01-01

This study examines the hegemony of political power on the discipline of human geography in Turkey. Throughout the history of the country, human geography curricula have been aligned with the nationalist and hegemonic power politics of state authorities instead of being guided by universal norms, thus ignoring Turkey's sociopolitical and cultural…

Attracting Future Geographers: The Introductory Course.

ERIC Educational Resources Information Center

Trindell, Roger

The organization and content of an introductory human geography course instituted at Mansfield State University (Pennsylvania) to interest students in a geography major and possible geography career is described. Organized around basic geography "co-traditions," the course begins by examining geography's origin, purpose, and relation to other…

Effects of an Introductory Geography Course on Student Perceptions of Geography at the University of Idaho

ERIC Educational Resources Information Center

Bowlick, Forrest J.; Kolden, Crystal A.

2013-01-01

This case study surveyed students in geography courses at the University of Idaho, investigating perceptions of geography's role in their daily lives, relevance to careers or academics, and parts of their geographic skill. Primarily, white, younger than 20, gender-balanced students in Introduction to Physical Geography and Human Geography courses…

Mobile Learning in a Human Geography Field Course

ERIC Educational Resources Information Center

Jarvis, Claire; Tate, Nicholas; Dickie, Jennifer; Brown, Gavin

2016-01-01

This article reports on reusable mobile digital learning resources designed to assist human geography undergraduate students in exploring the geographies of life in Dublin. Developing active learning that goes beyond data collection to encourage observation and thinking in the field is important. Achieving this in the context of large class sizes…

Examining the Relationships between Metacognition, Self-Regulation and Critical Thinking in Online Socratic Seminars for High School Social Studies Students

ERIC Educational Resources Information Center

Lee, Shih-Ting

2009-01-01

This study examined the relationships between metacognition, self-regulation and students' critical thinking skills and disposition in online Socratic Seminars for ninth grade World Geography and Culture students. Participants of this study came from six intact pre-AP (Pre-Advanced Placement) classes in a public high school in south central Texas…

Human geography in the French Institute: new discipline or missed opportunity?

PubMed

Staum, M S

1987-10-01

The geography section of the Class of Moral and Political Sciences of the French National Institute, which was in existence from December 1795 to January 1803, responded inadequately to the theoretical challenges of Montesquieu, the hygienists, Volney, and Degérando to study thoroughly native peoples to determine the effects of physical geographic conditions on the body and mind. Most geographers had no interest in human geography, and even statistical geography received only superficial discussion. Despite the emergence of the scientific journal, only a few authors partly transcended the stereotypes of the noble-ignoble savage. The only expedition partly planned by the Institute in this period had an ambitious exploration program that precluded a linguistically sophisticated study of native peoples. Bonaparte's dissolution of the Class hindered further opportunities for studying human geography during the Empire.

Environmental Education and Geography of Complexity

ERIC Educational Resources Information Center

Cecioni, Ester

2005-01-01

Geography is defined as "a transition point between natural temporality and human temporality" (Maragliano, 1998). Presented like this, geography seems, at least at first sight, to assume an inexorable function as a linking discipline between nature and society. Unfortunately this pivotal role is not realised, given that geography is…

Why Geography Matters.

ERIC Educational Resources Information Center

McDougall, Walter A.

2001-01-01

It is important to learn geography, yet most Americans leave school functionally illiterate in geography. Geography is fundamental to student maturation, the process of true education, and it is a springboard to every other science and humanities subject. Knowledge of maps and geographical information is crucial to the examination of economic,…

"Lesbian Migrants in the Gentrified Valley" and "Other" Geographies of Rural Gentrification

ERIC Educational Resources Information Center

Smith, Darren P.; Holt, Louise

2005-01-01

This paper explores the migration and cultural consumption practices of lesbian households within processes of rural change. Taking forward Phillips' (2004. Progress in Human Geography 28, 5-30) discussion of neglected geographies of rural gentrification, and building upon Halfacree's (2001. International Journal of Population Geography 7,…

Tuning the Field Trip: Audio-Guided Tours as a Replacement for 1-Day Excursions in Human Geography

ERIC Educational Resources Information Center

Wissmann, Torsten

2013-01-01

Educators are experiencing difficulties with 1-day field trips in human geography. Instead of teaching students how to apply theory in the field and learn to "sense" geography in everyday life, many excursions have degraded into tourist-like events where lecturers try to motivate rather passive students against a noisy urban backdrop.…

Teaching about Human Geography.

ERIC Educational Resources Information Center

Schlene, Vickie J.

1991-01-01

Presents a sampling of items from the ERIC database concerning the teaching of human geography. Includes documents dealing with Africa, Asia, the United States, Canada, Antarctica, and geographic concepts. Explains how to obtain ERIC documents. (SG)

Strengthening the ties between university and school - Bilingual geography is the future for our multifarious subject

NASA Astrophysics Data System (ADS)

Barnikel, F.

2003-04-01

An incessantly growing interaction between numerous fields of human activity asks for an open-minded approach and interdisciplinarity. No subject matches geography when it comes to bridging the gaps between different aspects of human life. Geography does not only describe, analyse and explain the "natural" state of the world we live in, it does also connect the disciplines within the physical branch of the subject with disciplines in the human or anthropogenic part, which describes the state of the world "as is". Geography is, therefore, in itself multi-disciplinary. Considering the immense importance of geography as the subject dealing with our environment and facing the fact that it is this environment which is already endangered by the multiple forms of human interference, geography and its multi-disciplinary character deserve even increased attention. The growth of the world's population, future climatic change and shortages of natural resources add to the importance of geography as the one subject in school dealing with these problems. In our societies, which are constantly growing together in political and economic issues, the structures of communication additionally mainly rely on an easily accessible and widely spread language like English to serve the needs of modern international contact. In Bavaria, the signs of the times have been recognized quite early. Nearly 8000 pupils at more than 80 high-level secondary schools ("Gymnasien") attend bilingual teaching, a large part of which is performed in geography. The Adolf-Weber-Gymnasium serves as an example, since it has the largest group of pupils instructed in bilingual geography in Munich. Next term, more than 150 boys and girls from five grades will be taught geography in English. Our goal is, in contrast to concepts of bilingual teaching in some other German states, not only to improve the language capability of our pupils. It is more an investment in scientific propaedeutics. It strenghtens the ties between university and school, since it enables future students to comprehend the character of geography and the aspects of its underlying diversity, and it, consequently, improves the students' ability to understand and solve geographical problems of the future.

Ohio Geographers: Recent Research Themes. Volume Number 2: 1974.

ERIC Educational Resources Information Center

Roder, Wolf, Ed.; Shelton, Marlyn L., Ed.

Ten professional geography research papers presented at the Geography Section of the 1974 annual meeting of the Ohio Academy of Science are provided. Six of the papers may be considered to fall under the broad classification of human geography, two others are about physical geography, while the remaining two seek to improve the craft of modern…

Early Instruction in Geography: An Exploration in the Ecology of Kindergarten and First-Grade Geography Education

ERIC Educational Resources Information Center

Walker, Scott L.

2007-01-01

This article presents an introductory study of early-grade level geography education in terms of human ecology using accepted cognitive process and knowledge dimensions related to learning. The central question addressed is "at what cognitive process and knowledge levels do kindergarten and first-grade teachers teach geography?" A tentative answer…

Scaling Health and Healthcare: Re-Presenting Thailand's HIV/AIDS Epidemic with World Regional Geography Students

ERIC Educational Resources Information Center

Del Casino Jr, Vincent

2004-01-01

Authors of world regional geography textbooks have recently become more interested in the broader theoretical changes that have emerged in human geography. Relying on feminist and other critical perspectives, concepts such as space, place and scale are being re-imagined in this 'new world regional geography'. This paper intervenes on behalf of a…

The Geography of Germany: Lessons for Teaching the Five Themes of Geography. Social Studies, Grades 9-12. Update 1997/1998.

ERIC Educational Resources Information Center

Blankenship, Glen; Tinkler, D. William

This packet contains five lessons related to the five themes of geography: location; place; human-environment interaction; movement; and region. The lessons are designed to support the teaching of courses in world geography, U.S. government/civics, and economics from a comparative U.S./German perspective. Lessons include: (1) "Location of…

Problems of Geography as General Education.

ERIC Educational Resources Information Center

Harper, Robert A.

The increasing interdependency and regional specialization of today's world demand a new approach to the teaching of introductory geography courses. By focusing on the interrelationship of physical, cultural, and economic geography, a course for general education students can foster development of the geographic perspective on human systems needed…

The Geography of Greenhouse Gas Emissions: Hands-On! Developing Active Learning Modules on the Human Dimensions of Global Change.

ERIC Educational Resources Information Center

Liverman, Diana; Solem, Michael

This learning module aims to engage students in problem solving, critical thinking, scientific inquiry, and cooperative learning. The module is appropriate for use in any introductory or intermediate undergraduate course that focuses on human-environment relationships. The module examines the geography of human activities that produce the major…

Perspectives on Cultural Geography in AP® Human Geography

ERIC Educational Resources Information Center

Hall, Christopher; Johnston-Anumonwo, Ibipo

2016-01-01

This article provides an overview of selected current concerns in cultural geography and the way it is taught. It includes coverage of cultural convergence and divergence, race and gender as culturally defined topics, and best teaching practices, including those related to analyzing controversial issues. Two important geographical models are laid…

Teaching Research Methods Courses in Human Geography: Critical Reflections

ERIC Educational Resources Information Center

Crooks, Valorie A.; Castleden, Heather; Tromp-van Meerveld, Ilja

2010-01-01

The authors reflect critically on their experiences of teaching research methods/methodology/techniques (MMT) courses in human geography for the first time. Through a highly reflexive process involving journaling, they engage with the broader scholarship of teaching and learning approach. Three themes characterize commonalities in their…

Population structure and cultural geography of a folktale in Europe

PubMed Central

Ross, Robert M.; Greenhill, Simon J.; Atkinson, Quentin D.

2013-01-01

Despite a burgeoning science of cultural evolution, relatively little work has focused on the population structure of human cultural variation. By contrast, studies in human population genetics use a suite of tools to quantify and analyse spatial and temporal patterns of genetic variation within and between populations. Human genetic diversity can be explained largely as a result of migration and drift giving rise to gradual genetic clines, together with some discontinuities arising from geographical and cultural barriers to gene flow. Here, we adapt theory and methods from population genetics to quantify the influence of geography and ethnolinguistic boundaries on the distribution of 700 variants of a folktale in 31 European ethnolinguistic populations. We find that geographical distance and ethnolinguistic affiliation exert significant independent effects on folktale diversity and that variation between populations supports a clustering concordant with European geography. This pattern of geographical clines and clusters parallels the pattern of human genetic diversity in Europe, although the effects of geographical distance and ethnolinguistic boundaries are stronger for folktales than genes. Our findings highlight the importance of geography and population boundaries in models of human cultural variation and point to key similarities and differences between evolutionary processes operating on human genes and culture. PMID:23390109

The Use of Fictional Literature in Teaching Concepts of Cultural Geography.

ERIC Educational Resources Information Center

Silverman, Sherman E.

This paper suggests that college-level geography instructors use novels to help students understand how people have interacted with particular environments within particular periods of time. In addition, it offers excerpts from approximately 20 novels that deal with topics often treated in human (cultural) geography courses. The author suggests…

Multiple Cultures of Doing Geography Facilitate Global Studies

ERIC Educational Resources Information Center

Ahamer, Gilbert

2013-01-01

Purpose: This article aims to explain why geography is a prime discipline for analysing globalisation and a multicultural view of Global Studies. The generic approach of human geography to first select an appropriate methodology is taken as a key approach. Design/methodology/approach: Concepts from aggregate disciplines such as history, economics,…

Reading Place, Reading Landscape: A Consideration of City as Text™ and Geography

ERIC Educational Resources Information Center

Hostetter, Ellen

2016-01-01

The fundamental concepts employed by City as Text™ (CAT)--the established experiential learning practice in honors education-and the discipline of geography, specifically the landscape tradition within human geography, share much in common. The overlaps offer CAT practitioners additional intellectual support from a source outside of honors while…

Concept Mapping Strategies: Content, Tools and Assessment for Human Geography

ERIC Educational Resources Information Center

Wehry, Stephanie; Monroe-Ossi, Heather; Cobb, Sharon; Fountain, Cheryl

2012-01-01

This article examines the use of concept mapping for formative and summative assessment of northeast Florida middle school students' knowledge of human geography. The students were participants in an afterschool, academic, college reach-out program that provided opportunities to test concept mapping strategies that support spatial thinking and…

Human Geography Trains Diverse Perspectives on Global Development

ERIC Educational Resources Information Center

Ahamer, Gilbert

2012-01-01

Purpose: Education for equity in global development and cultural diversity calls for professional capacity building to perceive diverse perspectives on complex procedures of globalisation. The discipline of human geography is such a "provider of perspectives". The purpose of this paper is to propose a historic series of how theories of geography…

Chromosome localization of human genes for clathrin adaptor polypeptides AP2{beta} and AP50 and the clathrin-binding protein, VCP

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

Druck, T.; Gu, Y.; Prabhala, G.

1995-11-01

Clathrin-coated vesicles, involved in endocytosis and Golgi processing, have a surface lattice containing clathrin triskelia and stoichiometric amounts of additional components termed {open_quotes}assembly proteins,{close_quotes} or APs. The AP form at the plasma membrane, AP2, is composed of two large subunits of 100-115 kDa, denoted AP2{alpha} and AP2{beta}, a medium chain of 50 kDa, designated AP50, and a small chain. We have determined human chromosomal locations of genes for a large AP2{beta} (CLAPB1) and a medium (CLAPM1) AP subunit and of a novel clathrin-binding protein, VCP, that binds clathrin simultaneously with A1`s. Chromosomal in situ hybridization of a human genomic clonemore » demonstrated that the CLAPM1 gene mapped to chromosome region 3q28. The gene for the CLAPB1 large subunit was mapped to 17q11.2-q12 by PCR amplification of an AP2{beta} fragment from a panel of rodent-human hybrid DNAs. To map the human VCP sequence, a human-specific probe was made by RT-PCR of human mRNA using oligonucleotide primers from conserved regions of the porcine sequence. The amplified human fragment served as probe on Southern blots of hybrid DNAs to determine that the human VCP locus maps to chromosome region 9pter-q34. 13 refs., 2 figs.« less

The Geography of Germany: Lessons for Teaching the Five Themes of Geography. Social Studies, Grades 9-12. Update 2002.

ERIC Educational Resources Information Center

Blankenship, Glen; Tinkler, D. William

This instructional package, consisting of a text and 13 transparencies, is designed for high school classrooms. The five lessons in the instructional package relate to the "Five Themes of Geography" (Location, Place, Human-Environment Interaction, Movement, and Region) as promoted by the National Geographic Society. The lessons are…

Teaching Research through Field Studies: A Cumulative Opportunity for Teaching Methodology to Human Geography Undergraduates

ERIC Educational Resources Information Center

Panelli, Ruth; Welch, Richard V.

2005-01-01

Notwithstanding its iconic status within geography, the debate continues about how fieldwork should be taught to undergraduate students. The authors engage with this debate and argue that field studies should follow the teaching of research methodology. In this paper they review relevant literature on the place of fieldwork in geography training,…

Teaching across the Divide: Physical and Human Geographies of Hurricane Katrina

ERIC Educational Resources Information Center

Iveson, Kurt; Neave, Melissa

2010-01-01

This article critically reflects on our effort to "teach across the divide", by integrating physical and human geography in a new first-year course. We achieved this integration by structuring our course around a series of key events, in order to draw out the interaction of "natural" and "social" forces. After setting…

The Importance of Direct Experience: A Philosophical Defence of Fieldwork in Human Geography

ERIC Educational Resources Information Center

Hope, Max

2009-01-01

Human geography fieldwork is important. Research has shown that when students "see it for themselves" their enjoyment and understanding is enhanced. In addition it helps develop subject-specific and transferable skills, promotes 'active learning' and links theory to "real world" examples in a "spiral of learning".…

Overcoming Masculine Bias in Introductory College Human Geography: A Module Approach.

ERIC Educational Resources Information Center

Rengert, Arlene; Monk, Janice J.

This report describes a project launched under the auspices of the Association of American Geographers to produce a series of modules designed to increase and improve the representation of women in introductory college human geography courses. The project aimed to produce materials which could be used to supplement existing courses in diverse…

"Riding the Rip": An Experiential and Integrated Human-Physical Geography Curriculum in Costa Rica

ERIC Educational Resources Information Center

Brannstrom, Christian; Houser, Chris

2015-01-01

Integrating research into short-term study abroad programs is challenging because of language, fieldwork logistics, and traditional learning models based on passive classroom experiences. Experiential learning often makes use of research as experience, but relatively few examples integrate human and physical geography. Here, we describe an…

Genetics: A New Landscape for Medical Geography

PubMed Central

Carrel, Margaret; Emch, Michael

2014-01-01

The emergence and re-emergence of human pathogens resistant to medical treatment will present a challenge to the international public health community in the coming decades. Geography is uniquely positioned to examine the progressive evolution of pathogens across space and through time, and to link molecular change to interactions between population and environmental drivers. Landscape as an organizing principle for the integration of natural and cultural forces has a long history in geography, and, more specifically, in medical geography. Here, we explore the role of landscape in medical geography, the emergent field of landscape genetics, and the great potential that exists in the combination of these two disciplines. We argue that landscape genetics can enhance medical geographic studies of local-level disease environments with quantitative tests of how human-environment interactions influence pathogenic characteristics. In turn, such analyses can expand theories of disease diffusion to the molecular scale and distinguish the important factors in ecologies of disease that drive genetic change of pathogens. PMID:24558292

A Study of Planet Three: A World Geography/Social Studies Course.

ERIC Educational Resources Information Center

Graham, Duncan

This 12th grade course in world geography is based on the philosophical assumption that human beings on earth make up a global village of interdependent people. It is world geography with a planetary perspective--an inquiry into the nature of the planet and its dominant species, Homo Sapiens. Seven units cover the following topics on physical and…

The Geography of Germany, Lessons for Teaching the Five Themes of Geography. Social Studies Grades 9-12. Update 1994.

ERIC Educational Resources Information Center

Blankenship, Glen; Tinkler, D. William

These lessons, designed for high school classrooms, focus on the country of Germany in teaching the five themes of geography (location, place, human-environment interaction, movement, and region). The lessons can be used individually via integration into the curriculum or collectively used as a complete stand-alone unit. The lessons are desigend…

Video Documentaries in the Assessment of Human Geography Field Courses

ERIC Educational Resources Information Center

Mavroudi, Elizabeth; Jons, Heike

2011-01-01

This paper critically reviews the use of video documentaries in the assessment of human geography field courses. It aims to contribute to recent debates about the role of visual methods for developing active and deep learning in student-centred teaching. Based on four days of group work in Crete, 30 third-year students produced individual…

Reframing Photographic Research Methods in Human Geography: A Long-Term Reflection

ERIC Educational Resources Information Center

Hall, Tim

2015-01-01

This paper offers a long-term reflection on the introduction of a photographic research project into a third-year undergraduate Human Geography module. The findings indicate that, whilst the students valued the project, it did impact on their overall performance, their evaluation of the module and the ways in which they spoke about it. The paper…

A Lesson Plan for Advanced Placement Human Geography®: A Site Location Exercise for New Businesses

ERIC Educational Resources Information Center

Poleski, Matthew

2017-01-01

The lesson described in this article meets several needs for Advanced Placement Human Geography (APHG®) teachers. In the interest of preserving time in the classroom, this lesson is intended to be a capstone assignment, allowing students to synthesize several concepts of the APHG® curriculum, such as demography, economic development, and cultural…

Connecting High School and University Teachers in National and International Contexts: Perspectives from the 2012 Bangalore Workshop of the AAG-CGGE

ERIC Educational Resources Information Center

Basu, Pratyusha; Pawson, Eric; Akhter, Majed; Palmer, David; Mervine, Valerie M.

2014-01-01

This paper focuses on the Center for Global Geography Education teaching workshop held in Bangalore, India, in March 2012 which served as a collaborative forum linking geography teachers in secondary and higher education in the USA and India. It considers the inclusion of the Advanced Placement Human Geography teachers from the USA and the…

The Initial Training of Geography Teachers at the University of Porto: Model and Training, Practices and Representations

ERIC Educational Resources Information Center

Martins, Felisbela

2015-01-01

Since 2008, the initial training of Geography teachers in Portugal was combined with the initial training of History teachers. This forced union has led to implications in the practices and teaching of geography. This paper intends to explore the thoughts and actions of the student teachers at the Faculty of Arts and Humanities, University of…

Advanced Placement Human Geography and the Annual Meetings of the National Council for Geographic Education

ERIC Educational Resources Information Center

Sublett, Michael D.

2007-01-01

Members of the National Council for Geographic Education have been instrumental in the creation, launch, and early success of Advanced Placement Human Geography. Annual meetings of the Council have served as a forum for spreading the word about the course and its follow-up national examination and in helping teachers develop content confidence and…

Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal cardiac preparations.

PubMed

Vahlensieck, U; Bokník, P; Gombosová, I; Huke, S; Knapp, J; Linck, B; Lüss, H; Müller, F U; Neumann, J; Deng, M C; Scheld, H H; Jankowski, H; Schlüter, H; Zidek, W; Zimmermann, N; Schmitz, W

1999-02-01

Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to 158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.

Replacing positivism in medical geography.

PubMed

Bennett, David

2005-06-01

Revisiting debates about philosophical approaches in medical geography suggests that logical positivism may have been prematurely discarded. An analysis of authoritative texts in medical geography and their sources in human geography shows that logical positivism has been conflated with Comtean positivism, science, empiricism, quantification, science politics, scientism and so on, to produce the "standard version" of the all-purpose pejorative "positivism", which it is easy to dismiss as an evil. It is argued that the standard version fails to do justice to logical positivism, being constructed on sources which are at some distance from the logical positivist movement itself. An alternative approach is then developed, an historically and geographically situated interpretation of logical positivism as a deliberately and knowingly constructed oppositional epistemology within an oppressive and anti-scientific culture predicated on idealist intuitionism. Contrasting the standard version with this alternative reading of logical positivism suggests that much may have been lost in human, and thus, medical geography, by throwing out the logical positivist baby with the "positivism" bath water. It is concluded that continuing to unpack the standard version of logical positivism may identify benefits from a more nuanced appreciation of logical positivism, but it is premature to take these to the level of detailed impacts on the kinds of medical geographies that could be done or the ways of doing them.

Media development effectiveness of geography 3d muckups

NASA Astrophysics Data System (ADS)

Prasetya, S. P.; Daryono; Budiyanto, E.

2018-01-01

Geography examines geosphere phenomena that occurs in a space associated with humans on earth’s surface. Media 3D models are an important visual media in presenting spatial objects on the earth’s surface. This study aims to develop a decent 3D mockups media used for learning materials and test the effectiveness of media geography 3D mockups on learning outcomes. The study involved 90 students of Geography Education, Faculty of Social Sciences and Law, State University of Surabaya. Method development using a model of the Borg and Gall (1989) which has been modified into three stages, namely the introduction, development, and testing. The study produced instructional media 3D Muckups eligible to be used as a learning medium for the material hydrosphere geography, geology, and geomorphology. 3D mockups media use in learning geography materials can increase the activity of students, student interest and a positive response to raise the student learning outcomes as the material can be delivered more concrete geography. Based on observations conducted student activity occurs continuously increase in the use of 3D models for learning geography material.

Enhancing the earth-science content and inquiry basis of physical geography education in Singapore schools

NASA Astrophysics Data System (ADS)

McCaughey, J.; Chong, E.

2011-12-01

Singapore has a long tradition of geography education at the secondary and Junior College levels (ages 12-18). Although most geography teachers teach both human and physical geography, many of them have received more extensive university training in human geography. The Earth Obervatory of Singapore (EOS), a newly established research institute at Nanyang Technological University (NTU), is building an education and outreach program to integrate its research across formal and informal education. We are collaborating with the Singapore Ministry of Education to enhance the earth-science content and inquiry basis of physical geography education in Singapore classrooms. EOS is providing input to national curriculum, textbook materials, and teaching resources, as well as providing inquiry-based field seminars and workshops for inservice teachers. An upcoming 5-year "Our Dynamic Earth" exhibit at the Science Centre Singapore will be a centerpoint of outreach to younger students, their teachers and parents, and to the community at large. On a longer time scale, the upcoming undergraduate program in earth science at NTU, the first of its kind in Singapore, will provide a stream of earth scientists into the geography teaching workforce. Developing ties between EOS and the National Institute of Education will further enhance teacher training. With a highly centralized curriculum, small land area, high-performing student population, and key stakeholders eager to collaborate with EOS, Singapore presents an unusual opportunity to impact classrooms on a national scale.

Ecologic Niche Modeling and Spatial Patterns of Disease Transmission

PubMed Central

2006-01-01

Ecologic niche modeling (ENM) is a growing field with many potential applications to questions regarding the geography and ecology of disease transmission. Specifically, ENM has the potential to inform investigations concerned with the geography, or potential geography, of vectors, hosts, pathogens, or human cases, and it can achieve fine spatial resolution without the loss of information inherent in many other techniques. Potential applications and current frontiers and challenges are reviewed. PMID:17326931

Geography and glocal scale - generational conversion/Geografia i skala glokalna - przemiana generacyjna

NASA Astrophysics Data System (ADS)

Pirveli, Marika; Lewczuk, Barbara

2013-12-01

The proposed text presents a conceptual change in the scope of some of the key concepts in the light of the two dictionaries (Britannica and Human Geography Dictionary) and Anglo-Saxon publications about the future of geography. Then, it combines the concept of references to the ongoing interdisciplinary studies included in the structure of the University of the Second and Third Generation. Applications built this way are of two types: (1) referring to a fundamental change in the process within the human perception of the environment for generations X and Y, and (2) referring to the process of glocalization, glocal scale and premises of the University of the Third Generation (3GU)

Political Geography and the Environment.

ERIC Educational Resources Information Center

Steinberg, Phillip E.

1997-01-01

Reviews recent theoretical advances in political geography, particularly those that stress the political conflict behind the production of space. Discusses how this has impacted the study of environmental phenomena such as hazards, human-land relationships, development, and international environmental governance. Suggests ways that political…

A Quantitative Comparison of the Similarity between Genes and Geography in Worldwide Human Populations

PubMed Central

Wang, Chaolong; Zöllner, Sebastian; Rosenberg, Noah A.

2012-01-01

Multivariate statistical techniques such as principal components analysis (PCA) and multidimensional scaling (MDS) have been widely used to summarize the structure of human genetic variation, often in easily visualized two-dimensional maps. Many recent studies have reported similarity between geographic maps of population locations and MDS or PCA maps of genetic variation inferred from single-nucleotide polymorphisms (SNPs). However, this similarity has been evident primarily in a qualitative sense; and, because different multivariate techniques and marker sets have been used in different studies, it has not been possible to formally compare genetic variation datasets in terms of their levels of similarity with geography. In this study, using genome-wide SNP data from 128 populations worldwide, we perform a systematic analysis to quantitatively evaluate the similarity of genes and geography in different geographic regions. For each of a series of regions, we apply a Procrustes analysis approach to find an optimal transformation that maximizes the similarity between PCA maps of genetic variation and geographic maps of population locations. We consider examples in Europe, Sub-Saharan Africa, Asia, East Asia, and Central/South Asia, as well as in a worldwide sample, finding that significant similarity between genes and geography exists in general at different geographic levels. The similarity is highest in our examples for Asia and, once highly distinctive populations have been removed, Sub-Saharan Africa. Our results provide a quantitative assessment of the geographic structure of human genetic variation worldwide, supporting the view that geography plays a strong role in giving rise to human population structure. PMID:22927824

A quantitative comparison of the similarity between genes and geography in worldwide human populations.

PubMed

Wang, Chaolong; Zöllner, Sebastian; Rosenberg, Noah A

2012-08-01

Multivariate statistical techniques such as principal components analysis (PCA) and multidimensional scaling (MDS) have been widely used to summarize the structure of human genetic variation, often in easily visualized two-dimensional maps. Many recent studies have reported similarity between geographic maps of population locations and MDS or PCA maps of genetic variation inferred from single-nucleotide polymorphisms (SNPs). However, this similarity has been evident primarily in a qualitative sense; and, because different multivariate techniques and marker sets have been used in different studies, it has not been possible to formally compare genetic variation datasets in terms of their levels of similarity with geography. In this study, using genome-wide SNP data from 128 populations worldwide, we perform a systematic analysis to quantitatively evaluate the similarity of genes and geography in different geographic regions. For each of a series of regions, we apply a Procrustes analysis approach to find an optimal transformation that maximizes the similarity between PCA maps of genetic variation and geographic maps of population locations. We consider examples in Europe, Sub-Saharan Africa, Asia, East Asia, and Central/South Asia, as well as in a worldwide sample, finding that significant similarity between genes and geography exists in general at different geographic levels. The similarity is highest in our examples for Asia and, once highly distinctive populations have been removed, Sub-Saharan Africa. Our results provide a quantitative assessment of the geographic structure of human genetic variation worldwide, supporting the view that geography plays a strong role in giving rise to human population structure.

Integrating Hydrology and Historical Geography in an Interdisciplinary Environmental Masters Program in Northern Ontario, Canada

NASA Astrophysics Data System (ADS)

Greer, Kirsten; James, April

2016-04-01

Research in hydrology and other sciences are increasingly calling for new collaborations that "…simultaneously explore the biogeophysical, social and economic forces that shape an increasingly human-dominated global hydrologic system…" (Vorosmarty et al. 2015, p.104). With many environmental programs designed to help students tackle environmental problems, these initiatives are not without fundamental challenges (for example, they are often developed around a single epistemology of positivism). Many environmental graduate programs provide narrow interdisciplinary training (within the sciences, or bridging to the social sciences) but do not necessarily engage with the humanities. Geography however, has a long tradition and history of bridging the geophysical, social sciences, and humanities. In this paper, we reflect on new programming in an Interdisciplinary Master's program in Northern Ontario, Canada, inspired by the rich tradition of geography. As Canada Research Chairs trained in different geographical traditions (historical geography and hydrology), we aim to bring together approaches in the humanities and geophysical sciences to understand hydrological and environmental change over time. We are teaching in a small, predominantly undergraduate University located in Northern Ontario, Canada, a region shaped significantly by colonial histories and resource development. The Masters of Environmental Studies/Masters of Environmental Sciences (MES/MESc) program was conceived from a decade of interdisciplinary dialogue across three undergraduate departments (Geography, Biology and Chemistry, History) to promote an understanding of both humanistic and scientific approaches to environmental issues. In the fall of 2015, as part of our 2015-2020 Canada Research Chair mandates, we introduced new initiatives to further address the integration of humanities and sciences to our graduate program. We believe the new generation of environmental scientists and practioners should be equipped to deal with the complex histories of colonialism, resource development, and scientific practices in addition to the skills necessary to conduct rigorous scientific environmental research. The following paper discusses some of our initiatives, including (1) a cross-disciplinary 'Workship', which assembled students, faculty and community members on a cruise of the 800 km2 Lake Nipissing to explore imaginative geographies of the lake; (2) a co-taught core course (Perspectives on the Environment) which included a theme specifically on the hydrosocial cycle (Linton and Budds 2014); and (3) student-group projects focused on developing interdisciplinary research proposals. Early reflections on this new programing is illustrating how existing literature in geography is adding ability to help bridge the sciences-humanities divides in our environmental graduate program.

Diadenosine polyphosphates release by human corneal epithelium.

PubMed

Carracedo, Gonzalo; Guzman-Aranguez, Ana; Loma, Patricia; Pintor, Jesús

2013-08-01

Diadenosine polyphosphates are a type of dinucleotides that have been detected in rabbit and human tears. However, their origin and their mechanism of release have not been fully elucidated. In this work we investigated whether the dinucleotides Ap4A and Ap5A can be released from human corneal epithelia as a consequence of shear stress stimuli. In in vitro experiments, concentrations of Ap4A and Ap5A before mechanical stimulus of stratified human corneal epithelial cells were 3.18 ± 0.43 nM and 0.81 ± 0.13 nM, respectively. After shear stimulation, concentrations significantly increased to 12.01 ± 2.19 nM for Ap4A and 2.83 ± 0.41 nM for Ap5A. No significant differences in lactate dehydrogenase activity were detected between non-stimulated stratified human corneal epithelial cells and cells exposed to mechanical shear-stress, indicating that the rise of dinucleotide levels was not due to cell lysis. In in vivo experiments, individuals subjected to a rise in blinking frequency showed a significant increase of Ap4A (∼25-fold when experiment was performed without anaesthetic and 75-fold with anaesthetic) and Ap5A concentration in tears (∼50-fold when experiment was performed without anaesthetic and 125-fold with anaesthetic). Shear-stress stimuli induces Ap4A and Ap5A release from human corneal epithelium, thus explaining the origin of these relevant compounds for the ocular surface biochemistry and physiology. Copyright © 2013 Elsevier Ltd. All rights reserved.

The human footprint in Mexico: physical geography and historical legacies.

PubMed

González-Abraham, Charlotte; Ezcurra, Exequiel; Garcillán, Pedro P; Ortega-Rubio, Alfredo; Kolb, Melanie; Bezaury Creel, Juan E

2015-01-01

Using publicly available data on land use and transportation corridors we calculated the human footprint index for the whole of Mexico to identify large-scale spatial patterns in the anthropogenic transformation of the land surface. We developed a map of the human footprint for the whole country and identified the ecological regions that have most transformed by human action. Additionally, we analyzed the extent to which (a) physical geography, expressed spatially in the form of biomes and ecoregions, compared to (b) historical geography, expressed as the spatial distribution of past human settlements, have driven the patterns of human modification of the land. Overall Mexico still has 56% of its land surface with low impact from human activities, but these areas are not evenly distributed. The lowest values are on the arid north and northwest, and the tropical southeast, while the highest values run along the coast of the Gulf of Mexico and from there inland along an east-to-west corridor that follows the Mexican transversal volcanic ranges and the associated upland plateau. The distribution of low- and high footprint areas within ecoregions forms a complex mosaic: the generally well-conserved Mexican deserts have some highly transformed agro-industrial areas, while many well-conserved, low footprint areas still persist in the highly-transformed ecoregions of central Mexico. We conclude that the spatial spread of the human footprint in Mexico is both the result of the limitations imposed by physical geography to human development at the biome level, and, within different biomes, of a complex history of past civilizations and technologies, including the 20th Century demographic explosion but also the spatial pattern of ancient settlements that were occupied by the Spanish Colony.

The Human Footprint in Mexico: Physical Geography and Historical Legacies

PubMed Central

Ortega-Rubio, Alfredo; Kolb, Melanie; Bezaury Creel, Juan E.

2015-01-01

Using publicly available data on land use and transportation corridors we calculated the human footprint index for the whole of Mexico to identify large-scale spatial patterns in the anthropogenic transformation of the land surface. We developed a map of the human footprint for the whole country and identified the ecological regions that have most transformed by human action. Additionally, we analyzed the extent to which (a) physical geography, expressed spatially in the form of biomes and ecoregions, compared to (b) historical geography, expressed as the spatial distribution of past human settlements, have driven the patterns of human modification of the land. Overall Mexico still has 56% of its land surface with low impact from human activities, but these areas are not evenly distributed. The lowest values are on the arid north and northwest, and the tropical southeast, while the highest values run along the coast of the Gulf of Mexico and from there inland along an east-to-west corridor that follows the Mexican transversal volcanic ranges and the associated upland plateau. The distribution of low- and high footprint areas within ecoregions forms a complex mosaic: the generally well-conserved Mexican deserts have some highly transformed agro-industrial areas, while many well-conserved, low footprint areas still persist in the highly-transformed ecoregions of central Mexico. We conclude that the spatial spread of the human footprint in Mexico is both the result of the limitations imposed by physical geography to human development at the biome level, and, within different biomes, of a complex history of past civilizations and technologies, including the 20th Century demographic explosion but also the spatial pattern of ancient settlements that were occupied by the Spanish Colony. PMID:25803839

Alkaline Phosphatase, an Unconventional Immune Protein.

PubMed

Rader, Bethany A

2017-01-01

Recent years have seen an increase in the number of studies focusing on alkaline phosphatases (APs), revealing an expanding complexity of function of these enzymes. Of the four human AP (hAP) proteins, most is known about tissue non-specific AP (TNAP) and intestinal AP (IAP). This review highlights current understanding of TNAP and IAP in relation to human health and disease. TNAP plays a role in multiple processes, including bone mineralization, vitamin B6 metabolism, and neurogenesis, is the genetic cause of hypophosphatasia, influences inflammation through regulation of purinergic signaling, and has been implicated in Alzheimer's disease. IAP regulates fatty acid absorption and has been implicated in the regulation of diet-induced obesity and metabolic syndrome. IAP and TNAP can dephosphorylate bacterial-derived lipopolysaccharide, and IAP has been identified as a potential regulator of the composition of the intestinal microbiome, an evolutionarily conserved function. Endogenous and recombinant bovine APs and recombinant hAPs are currently being explored for their potential as pharmacological agents to treat AP-associated diseases and mitigate multiple sources of inflammation. Continued research on these versatile proteins will undoubtedly provide insight into human pathophysiology, biochemistry, and the human holobiont.

Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin.

PubMed

Mueller, Kate R; Balamurugan, A N; Cline, Gary W; Pongratz, Rebecca L; Hooper, Rebecca L; Weegman, Bradley P; Kitzmann, Jennifer P; Taylor, Michael J; Graham, Melanie L; Schuurman, Henk-Jan; Papas, Klearchos K

2013-01-01

Porcine islet xenotransplantation is considered a potential cell-based therapy for type 1 diabetes. It is currently being evaluated in diabetic nonhuman primates (NHP) to assess safety and efficacy of the islet product. However, due to a variety of distinct differences between the respective species, including the insulin secretory characteristics of islets, the suitability and predictive value of the preclinical model in the extrapolation to the clinical setting remain a critical issue. Islets isolated from human (n = 3), NHP (n = 2), adult pig (AP, n = 3), and juvenile pig (JP, n = 4) pancreata were perifused with medium at basal glucose (2.5 mm) followed by high glucose (16.7 mm) concentrations. The total glucose-stimulated insulin secretion (GSIS) was calculated from generated insulin secretion profiles. Nonhuman primate islets exhibited GSIS 3-fold higher than AP islets, while AP and JP islets exhibited GSIS 1/3 and 1/30 of human islets, respectively. The insulin content of NHP and AP islets was similar to that of human islets, whereas that of JP islets was 1/5 of human islets. Despite the fact that human, NHP, and AP islets contain similar amounts of insulin, the much higher GSIS for NHP islets than for AP and JP islets suggests the need for increased dosing of islets from JP and AP in pig-to-NHP transplantation. Porcine islet xenotransplantation to humans may require significantly higher dosing given the lower GSIS of AP islets compared to human islets. © 2013 John Wiley & Sons A/S.

Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate and porcine origin

PubMed Central

Mueller, Kate R; Balamurugan, A.N.; Cline, Gary W; Pongratz, Rebecca L; Hooper, Rebecca L; Weegman, Bradley P; Kitzmann, Jennifer P; Taylor, Michael J; Graham, Melanie L; Schuurman, Henk-Jan; Papas, Klearchos K

2014-01-01

Background Porcine islet xenotransplantation is considered a potential cell-based therapy for type 1 diabetes. It is currently being evaluated in diabetic nonhuman primates (NHP) to assess safety and efficacy of the islet product. However, due to a variety of distinct differences between the respective species, including the insulin secretory characteristics of islets, the suitability and predictive value of the preclinical model in the extrapolation to the clinical setting remains a critical issue. Methods Islets isolated from human (n=3), NHP (n=2), adult pig (AP, n=3) and juvenile pig (JP, n=3) pancreata were perifused with medium at basal glucose (2.5mM) followed by high glucose (16.7mM) concentrations. The total glucose-stimulated insulin secretion (GSIS) was calculated from generated insulin secretion profiles. Results NHP islets exhibited GSIS 3-fold higher than human islets, while AP and JP islets exhibited GSIS 1/3 and 1/16 of human islets, respectively. The insulin content of NHP and AP islets was similar to that of human islets, whereas that of JP islets was 1/3 of human islets. Conclusion Despite the fact that human, NHP, and AP islets contain similar amounts of insulin, the much higher GSIS for NHP islets than for human, AP and JP islets suggests the need for increased dosing of islets from JP and AP in pig-to-NHP transplantation which may be substantially higher than that required for humans. Finally, porcine islet xenotransplantation to humans may require significantly higher dosing given the lower GSIS of AP islets compared to human islets. PMID:23384163

Geography and Viticulture: Rationale and Resource.

ERIC Educational Resources Information Center

Blij, Harm Jan de

1983-01-01

The study of viticulture (the growing of grapes) can illustrate the practical applications of geography: spatial orientation, focus on natural environment, human-land interaction, and concern with the properties and characteristics of regions. A suggested course outline is given, as well as a listing of resources about viticulture. (IS)

Assessing Sustainability Teaching and Learning in Geography Education

ERIC Educational Resources Information Center

Widener, Jeffrey M.; Gliedt, Travis; Tziganuk, Ashlee

2016-01-01

Purpose: This study aims to understand if geographers, who teach in a new sustainability program, are conveying new knowledge, understanding, skills and competence about the integrated and holistic concept of "sustainability", rather than individual human-environmental issues to the students. In other words, are geography professors…

Lines

ERIC Educational Resources Information Center

Mires, Peter B.

2006-01-01

National Geography Standards for the middle school years generally stress the teaching of latitude and longitude. There are many creative ways to explain the great grid that encircles our planet, but the author has found that students in his college-level geography courses especially enjoy human-interest stories associated with lines of latitude…

The geography and human cultural resources working group of the EROS program

NASA Technical Reports Server (NTRS)

Gerlach, A. C.

1972-01-01

The functions, activities, and objectives of the Geography and Human-Cultural Resources Working Group of the EROS program are outlined. The Group's primary function is to coordinate remote sensing experiments of physical scientists and the needs of socioeconomic and culturally orientated planners, policy makers, administrators, and other user groups. Other functions of the Group include land use analysis, resource mapping, and development of an operational automatic information system receptive to land use and environmental data.

Fieldwork Lesson based on" the International Geography Olympiad" (iGeo)

NASA Astrophysics Data System (ADS)

Otani, Seiichi

2017-04-01

Japanese social studies consist of three fields. That's geography, history and civics. About geographical studies in Japan, it has a lot of contents of human geography and has little contents of natural geography. I think that Japanese social studies teachers should teach more natural geography contents for ESD. 　 There is a fieldwork lesson in geographical studies in Japan. This is the educational activity by which body and head were used. But in fact, fieldwork lessons are not performed in many Japanese junior high schools. I was a leader of iGeo2012 (in Germany). iGeo is held by three tests; Multimedia tests, Writing tests and Fieldwork tests. The test is included of a lot of contents of natural geography. And there are two skills that students acquire through the fieldwork test in iGeo. One is a map making skill, the other is decision making skill. Japanese students need more knowledge of natural geography. And those are not enough skills for Japanese students. So I did a fieldwork lesson based on iGeo's fieldwork test. The fieldwork lesson was performed around the school. It was also performed under the point of natural geography. After the lessons, students could improve map making skill. Because a lot of maps made by students in this lesson got prize of map contest in Japan. Some maps were included the view of natural geography.

Perspectives on Economic Geography in AP® Human Geography

ERIC Educational Resources Information Center

Moore, Jon; Hunt, Allison

2016-01-01

Economic geographers have traditionally concerned themselves with the primary and secondary sectors of the economy. As the world becomes more service-oriented, however, as much attention must be paid to the service economy and the role of technology. This article focuses on deindustrialization and the rise of the contemporary service--and…

Main Street: Teaching Elementary School Students Standards-Based Urban Geography.

ERIC Educational Resources Information Center

Hurt, Douglas A.

1997-01-01

Describes a lesson plan that uses Main Street images of three towns to encourage students to recognize and compare human and physical characteristics of places. The lesson teaches the geographic concepts of site (absolute location) and situation (relative location) as well as introducing students to urban geography. (MJP)

Teaching Young Children Basic Concepts of Geography: A Literature-Based Approach.

ERIC Educational Resources Information Center

Hannibal, Mary Anne Zeitler; Vasiliev, Ren; Lin, Qiuyun

2002-01-01

This article advocates a literature-based instructional approach as a way of promoting geographic awareness in early childhood classrooms. Instruction focuses on basic geography concepts of location, place, human- environment interaction, movement, and region. Examples of children's picture books are included to show what early childhood teachers…

TRO40303 Ameliorates Alcohol-Induced Pancreatitis Through Reduction of Fatty Acid Ethyl Ester–Induced Mitochondrial Injury and Necrotic Cell Death

PubMed Central

Javed, Muhammad Ahsan; Wen, Li; Awais, Muhammad; Latawiec, Diane; Huang, Wei; Chvanov, Michael; Schaller, Sophie; Bordet, Thierry; Michaud, Magali; Pruss, Rebecca; Tepikin, Alexei; Criddle, David; Sutton, Robert

2018-01-01

Objectives Mitochondrial permeability transition pore inhibition is a promising approach to treat acute pancreatitis (AP). We sought to determine (i) the effects of the mitochondrial permeability transition pore inhibitor 3,5-seco-4-nor-cholestan-5-one oxime-3-ol (TRO40303) on murine and human pancreatic acinar cell (PAC) injury induced by fatty acid ethyl esters (FAEEs) or taurolithocholic acid-3-sulfate and (ii) TRO40303 pharmacokinetics and efficacy in experimental alcoholic AP (FAEE-AP). Methods Changes in mitochondrial membrane potential (Δψm), cytosolic Ca2+ ([Ca2+]c), and cell fate were examined in freshly isolated murine or human PACs by confocal microscopy. TRO40303 pharmacokinetics were assessed in cerulein-induced AP and therapeutic efficacy in FAEE-AP induced with palmitoleic acid and ethanol. Severity of AP was assessed by standard biomarkers and blinded histopathology. Results TRO40303 prevented loss of Δψm and necrosis induced by 100 μM palmitoleic acid ethyl ester or 500 μM taurolithocholic acid-3-sulfate in murine and human PACs. Pharmacokinetic analysis found TRO40303 accumulated in the pancreas. A single dose of 3 mg/kg TRO40303 significantly reduced serum amylase (P = 0.043), pancreatic trypsin (P = 0.018), and histopathology scores (P = 0.0058) in FAEE-AP. Conclusions TRO40303 protects mitochondria and prevents necrotic cell death pathway activation in murine and human PACs, ameliorates the severity of FAEE-AP, and is a candidate drug for human AP. PMID:29200128

GeoHumanities, GIScience and Smart City Lifeworld approaches to geography and the new human condition

NASA Astrophysics Data System (ADS)

Travis, Charles

2017-09-01

The New Human Condition (NHC) is perhaps the largest cognitive challenge in history to human intelligence and agency and concerns our species' ability to cope with the consequences and responsibilities of being the major driver of planetary change in the twenty-first century (Pálsson et al., 2013; Holm et al., 2015). But despite long held assumptions about intra-disciplinary engagements between its ;human; and ;physical; branches, geography's weakness as a discipline is that it has yet to gather sufficient momentum to collectively shape and implement practical and sustainable climate change policies and actions (Castree, 2014a). However, by considering together the heuristic values of the concepts of the Anthropocene and Planetary Boundaries, the Anglo-American sphere of geography recognizes in either ironic, or unconscious manners that a new strand of environmental determinism (discredited by geographical thought and practice in the early twentieth century) has re-emerged to elide the role of human agency and broadly dominate the discussion of climate change. Mike Hulme (2011, 247) states that ;climate determinism; is ;a form of analysis and prediction in which climate is first extracted from the matrix of interdependencies that shape human life within the physical world;. Within this discourse it is often the biophysical sphere that is employed to explain the course of human behavior; consequently, this dominating perspective threatens to skew our predictions and understandings of future societies, cultures, climates and destinies. Climate change will certainly constrain human agency, but it also creates the potential for geography to play to its intra and inter disciplinary strengths and begin discussing and addressing human-environmental dilemmas in practical and realistic ways; and secondly, seize the climate change crisis as an opportunity to study where, why and for whom global environmental change matters. Firstly, this paper considers a theoretical balance between the NHC, the Anthropocene and Planetary Boundaries as a way forward for geography to begin addressing the common dilemma of climate change. Within this consideration it engages Anne Buttimer's geographical translation of Martin Heidegger's lebenswelt as a dimension of the NHC. Secondly, the paper discusses how GeoHumanities and GIScience integrations with phenomenology, the digital and environmental humanities and social media generated ;Big-Data; can explore the perceptual scales and scopes of the NHC/Anthropocene/Planetary Boundaries conceptual triad. Lastly, it argues that such integrations are salient to the study of emerging Smart City Lifeworlds as a means to engage the increasing urban agencies of global climate change driven by the vagaries of the human condition.

One-step affinity tag purification of full-length recombinant human AP-1 complexes from bacterial inclusion bodies using a polycistronic expression system

PubMed Central

Wang, Wei-Ming; Lee, A-Young; Chiang, Cheng-Ming

2008-01-01

The AP-1 transcription factor is a dimeric protein complex formed primarily between Jun (c-Jun, JunB, JunD) and Fos (c-Fos, FosB, Fra-1, Fra-2) family members. These distinct AP-1 complexes are expressed in many cell types and modulate target gene expression implicated in cell proliferation, differentiation, and stress responses. Although the importance of AP-1 has long been recognized, the biochemical characterization of AP-1 remains limited in part due to the difficulty in purifying full-length, reconstituted dimers with active DNA-binding and transcriptional activity. Using a combination of bacterial coexpression and epitope-tagging methods, we successfully purified all 12 heterodimers (3 Jun × 4 Fos) of full-length human AP-1 complexes as well as c-Jun/c-Jun, JunD/JunD, and c-Jun/JunD dimers from bacterial inclusion bodies using one-step nickel-NTA affinity tag purification following denaturation and renaturation of coexpressed AP-1 subunits. Coexpression of two constitutive components in a dimeric AP-1 complex helps stabilize the proteins when compared with individual protein expression in bacteria. Purified dimeric AP-1 complexes are functional in sequence-specific DNA binding, as illustrated by electrophoretic mobility shift assays and DNase I footprinting, and are also active in transcription with in vitro-reconstituted human papillomavirus (HPV) chromatin containing AP-1-binding sites in the native configuration of HPV nucleosomes. The availability of these recombinant full-length human AP-1 complexes has greatly facilitated mechanistic studies of AP-1-regulated gene transcription in many biological systems. PMID:18329890

Diadenosine tetraphosphate (Ap4A) and triphosphate (Ap3A) signaling of human sperm motility.

PubMed

Chan, P J; Su, B C; Tredway, D R

1991-01-01

The ubiquitous dinucleotide polyphosphate, diadenosine tetraphosphate (Ap4A), has been shown to be a signal molecule for DNA replication in mammalian cells. In this study, Ap4A and a related compound, diadenosine triphosphate (Ap3A), were tested for possible signaling functions in human spermatozoa. A computerized automated semen analyzer was used to detect changes in spermatozoa motility parameters. Cryopreserved-thawed donor spermatozoa were washed and incubated in 0.1 mM Ap4A, 0.1 mM Ap3A, or control medium. The data indicated that both Ap4A and Ap3A decreased the percentage of motile spermatozoa after 4 or more hours of incubation in vitro. The two dinucleotide polyphosphates caused an increase in the amplitude of lateral spermatozoa head displacement parameter only at the start of incubation. The other spermatozoa kinematic parameters were unaffected. No opposing ying-yang dual actions of Ap4A to Ap3A were seen. From the results, Ap4A and Ap3A were observed to be potential inhibitory signals of spermatozoa motility after prolonged exposure.

Advances in Bacterial Methionine Aminopeptidase Inhibition

PubMed Central

Helgren, Travis R.; Wangtrakuldee, Phumvadee; Staker, Bart L.; Hagen, Timothy J.

2016-01-01

Methionine aminopeptidases (MetAPs) are metalloenzymes that cleave the N-terminal methionine from newly synthesized peptides and proteins. These MetAP enzymes are present in bacteria, and knockout experiments have shown that MetAP activity is essential for cell life, suggesting that MetAPs are good antibacterial drug targets. MetAP enzymes are also present in the human host and selectivity is essential. There have been significant structural biology efforts and over 65 protein crystal structures of bacterial MetAPs are deposited into the PDB. This review highlights the available crystallographic data for bacterial MetAPs. Structural comparison of bacterial MetAPs with human MetAPs highlights differences that can lead to selectivity. In addition, this review includes the chemical diversity of molecules that bind and inhibit the bacterial MetAP enzymes. Analysis of the structural biology and chemical space of known bacterial MetAP inhibitors leads to a greater understanding of this antibacterial target and the likely development of potential antibacterial agents. PMID:26268344

Immersive Virtual Worlds in University-Level Human Geography Courses

ERIC Educational Resources Information Center

Dittmer, Jason

2010-01-01

This paper addresses the potential for increased deployment of immersive virtual worlds in higher geographic education. An account of current practice regarding popular culture in the geography classroom is offered, focusing on the objectification of popular culture rather than its constitutive role vis-a-vis place. Current e-learning practice is…

The Periglacial Environment, Permafrost, and Man.

ERIC Educational Resources Information Center

Price, Larry W.

This booklet contains resource material on cold climate phenomena and their influences on humans. It is intended for use by teachers and students in college-level geography courses as a supplement to existing textbooks and as a means of filling the gap between significant resources in geography and readily accessible materials. The material is…

"Change4Life for Your Kids": Embodied Collectives and Public Health Pedagogy

ERIC Educational Resources Information Center

Evans, Bethan; Colls, Rachel; Horschelmann, Kathrin

2011-01-01

Recent work in human geography has begun to explore the fluidity of bodily boundaries and to foreground the connectedness of bodies to other bodies/objects/places. Across multiple subdisciplinary areas, including health, children's and feminist geographies, geographers have begun to challenge the notion of a singular, bounded body by highlighting…

Using Web-Based GIS in Introductory Human Geography

ERIC Educational Resources Information Center

Songer, Lynn C.

2010-01-01

Advocates for using a geographic information system (GIS) in education assert that GIS improves student learning. However, studies to clarify the relationship between learning and using GIS are still needed. This study examines the effects of using Web-based GIS maps in place of paper maps on students' geography content knowledge and motivation…

Double-Play: Using Minor League Baseball to Apply Themes and Standards in Human Geography Courses

ERIC Educational Resources Information Center

Zeitler, Ezra

2013-01-01

Growing student interest in sports provides geography teachers with a special opportunity to make connections between it and fundamental concepts in the discipline. This article examines the structure, arrangement, relationships, and distinctions among minor league baseball franchise locations, stadia, and team names, and presents examples of…

The Geography of Germany: Lessons for Teaching the Five Themes of Geography.

ERIC Educational Resources Information Center

Blankenship, Glen; Tinkler, D. William

This activity guide contains five lessons. Lesson 1 deals with "Location of Germany on the Earth's Surface" with two activities: (1) "Germany's Location in the World"; and (2) "Germany's Location in Europe." Lesson 2 is on the "Physical and Human Characteristics of Germany" with four activities on: (1)…

The New Faces of Europe. Secondary Education.

ERIC Educational Resources Information Center

Foucher, Michel

This monograph, published as part of the project "A Secondary Education for Europe," offers some basic data on the contemporary human geography of the European continent, with a focus on central and eastern Europe. The document first describes civic issues in the teaching of geography and cartography of the new Europe. The basic…

Makiguchi Tsunesaburo and Language, Value-Creative Composition Instruction, and the Geography of Identity in Community Studies: A Response to Politicized Imagining and Ineffective Critical Approaches

ERIC Educational Resources Information Center

Goulah, Jason

2013-01-01

In this article, the author examines Makiguchi Tsunesaburo's philosophy and practice of human geography ("jinsei chirigaku"), community studies ("kyodoka"), and composition instruction based on "value-creating pedagogy" ("soka kyoikugaku") for thinking through and responding to two competing trends…

The Value and Use of Music in Geographic Education.

ERIC Educational Resources Information Center

Wise, John H.

This paper provides examples of how music can be used in geography instruction at the elementary, secondary, or college levels. The occasional use of music can foster imagination and promote greater aesthetic awareness with regard to landscapes and human situations. Many concepts and terms in physical geography can be lined with music. A good…

Inhibition of Mycobacterium tuberculosis Methionine Aminopeptidases by Bengamide Derivatives

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

Lu, Jing-Ping; Yuan, Xiu-Hua; Yuan, Hai

Methionine aminopeptidase (MetAP) carries out an essential function of protein N-terminal processing in many bacteria and is a promising target for the development of novel antitubercular agents. Natural bengamides potently inhibit the proliferation of mammalian cells by targeting MetAP enzymes, and the X-ray crystal structure of human type 2 MetAP in complex with a bengamide derivative reveals the key interactions at the active site. By preserving the interactions with the conserved residues inside the binding pocket while exploring the differences between bacterial and human MetAPs around the binding pocket, seven bengamide derivatives were synthesized and evaluated for inhibition of MtMetAP1amore » and MtMetAP1c in different metalloforms, inhibition of M. tuberculosis growth in replicating and non-replicating states, and inhibition of human K562 cell growth. Potent inhibition of MtMetAP1a and MtMetAP1c and modest growth inhibition of M. tuberculosis were observed for some of these derivatives. Crystal structures of MtMetAP1c in complex with two of the derivatives provided valuable structural information for improvement of these inhibitors for potency and selectivity.« less

Structure of a microsporidian methionine aminopeptidase type 2 complexed with fumagillin and TNP-470

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

Alvarado, J.; Nemkal, A; Sauder, J

2009-01-01

Microsporidia are protists that have been reported to cause infections in both vertebrates and invertebrates. They have emerged as human pathogens particularly in patients that are immunosuppressed and cases of gastrointestinal infection, encephalitis, keratitis, sinusitis, myositis and disseminated infection are well described in the literature. While benzimidazoles are active against many species of microsporidia, these drugs do not have significant activity against Enterocytozoon bieneusi. Fumagillin and its analogues have been demonstrated to have activity in vitro and in animal models of microsporidiosis and human infections due to E. bieneusi. Fumagillin and its analogues inhibit methionine aminopeptidase type 2. Encephalitozoon cuniculimore » MetAP2 (EcMetAP2) was cloned and expressed as an active enzyme using a baculovirus system. The crystal structure of EcMetAP2 was determined with and without the bound inhibitors fumagillin and TNP-470. This structure classifies EcMetAP2 as a member of the MetAP2c family. The EcMetAP2 structure was used to generate a homology model of the E. bieneusi MetAP2. Comparison of microsporidian MetAP2 structures with human MetAP2 provides insights into the design of inhibitors that might exhibit specificity for microsporidian MetAP2.« less

Human Papillomavirus Type 16 E6 Induces Self-Ubiquitination of the E6AP Ubiquitin-Protein Ligase

PubMed Central

Kao, Wynn H.; Beaudenon, Sylvie L.; Talis, Andrea L.; Huibregtse, Jon M.; Howley, Peter M.

2000-01-01

The E6 protein of the high-risk human papillomaviruses (HPVs) and the cellular ubiquitin-protein ligase E6AP form a complex which causes the ubiquitination and degradation of p53. We show here that HPV16 E6 promotes the ubiquitination and degradation of E6AP itself. The half-life of E6AP is shorter in HPV-positive cervical cancer cells than in HPV-negative cervical cancer cells, and E6AP is stabilized in HPV-positive cancer cells when expression of the viral oncoproteins is repressed. Expression of HPV16 E6 in cells results in a threefold decrease in the half-life of transfected E6AP. E6-mediated degradation of E6AP requires (i) the binding of E6 to E6AP, (ii) the catalytic activity of E6AP, and (iii) activity of the 26S proteasome, suggesting that E6-E6AP interaction results in E6AP self-ubiquitination and degradation. In addition, both in vitro and in vivo experiments indicate that E6AP self-ubiquitination results primarily from an intramolecular transfer of ubiquitin from the active-site cysteine to one or more lysine residues; however, intermolecular transfer can also occur in the context of an E6-mediated E6AP multimer. Finally, we demonstrate that an E6 mutant that is able to immortalize human mammary epithelial cells but is unable to degrade p53 retains its ability to bind and degrade E6AP, raising the possibility that E6-mediated degradation of E6AP contributes to its ability to transform mammalian cells. PMID:10864652

Experimental and clinical evidence of antioxidant therapy in acute pancreatitis

PubMed Central

Esrefoglu, Mukaddes

2012-01-01

Oxidative stress has been shown to play an important role in the pathogenesis of acute pancreatitis (AP). Antioxidants, alone or in combination with conventional therapy, should improve oxidative-stress-induced organ damage and therefore accelerate the rate of recovery. In recent years, substantial amounts of data about the efficiency of antioxidants against oxidative damage have been obtained from experiments with rodents. Some of these antioxidants have been found beneficial in the treatment of AP in humans; however, at present there is insufficient clinical data to support the benefits of antioxidants, alone or in combination with conventional therapy, in the management of AP in humans. Conflicting results obtained from experimental animals and humans may represent distinct pathophysiological mechanisms mediating tissue injury in different species. Further detailed studies should be done to clarify the exact mechanisms of tissue injury in human AP. Herein I tried to review the existing experimental and clinical studies on AP in order to determine the efficiency of antioxidants. The use of antioxidant enriched nutrition is a potential direction of clinical research in AP given the lack of clues about the efficiency and safety of antioxidant usage in patients with AP. PMID:23112545

Anticancer activity of Astragalus polysaccharide in human non-small cell lung cancer cells.

PubMed

Wu, Chao-Yan; Ke, Yuan; Zeng, Yi-Fei; Zhang, Ying-Wen; Yu, Hai-Jun

2017-01-01

We have reported that Chinese herbs Astragalus polysaccharide (APS) can inhibit nuclear factor kappaB (NF-κB) activity during the development of diabetic nephropathy in mice. NF-κB plays important roles in genesis, growth, development and metastasis of cancer. NF-κB is also involved in the development of treatment resistance in tumors. Here we investigated the antitumor activity of APS in human non-small cell lung cells (A549 and NCI-H358) and the related mechanisms of action. The dose-effect and time-effect of antitumor of APS were determined in human lung cancer cell line A549 and NCI-H358. The inhibition effect of APS on the P65 mRNA and protein was detected by reverse transcriptase-PCR (RT-PCR) and Western blot in A549 cells respectively. The inhibition effect of APS on the p50, CyclinD1 and Bcl-xL protein was detected by Western blot in A549 cells respectively. The effect of APS on NF-κB transcription activity was measured with NF-κB luciferase detection. Finally, the nude mice A549 xenograft was introduced to confirm the antitumor activity of APS in vivo. Cell viability detection results indicated that APS can inhibit the proliferation of human lung cancer cell line A549 and NCI-H358 in the concentration of 20 and 40 mg/mL. NF-κB activator Phorbol 12-myristate13-acetate (PMA) can attenuate the antitumor activity of APS in both cell lines, but NF-κB inhibitor BAY 11-7082 (Bay) can enhance the effect of APS in both cell lines. In vivo APS can delay the growth of A549 xenograft in BALB/C nude mice. APS can down-regulate the expression of P65 mRNA and protein of A549 cells and decrease the expression of p50, CyclinD1 and Bcl-xL protein. The luciferase detection showed that the APS could reduce the P65 transcription activity in A549 cells. PMA can partially alleviate the inhibition activity of P65 transcription activity of APS in A549 cells, and Bay can enhance the down-regulation of the P65 transcription activity induced by APS in A549 cells. APS has a significant antitumor activity in human lung cancer cells A549 and NCI-H358. NF-κB inhibition may mediate the antitumor effect.

Less Talk More Drone: Social Research with UAVs

ERIC Educational Resources Information Center

Birtchnell, Thomas; Gibson, Chris

2015-01-01

There is a growing body of work in geography and sociology on the impact of drones on warfare, surveillance and civil protest. This paper assesses the challenges of using drones for teaching human geography and spatial social sciences. Affordable and expensive drones are now available in the market place; however, there has been next to no…

Creating Regional Futures: A Scenario-Based Inter- and Transdisciplinary Case Study as a Model for Applied Student-Centred Learning in Geography

ERIC Educational Resources Information Center

Fromhold-Eisebith, Martina; Freyer, Bernhard; Mose, Ingo; Muhar, Andreas; Vilsmaier, Ulli

2009-01-01

Human geography students face changing qualification requirements due to a shift towards new topics, educational tasks and professional options regarding issues of spatial development. This "practical turn" raises the importance of inter- and transdisciplinary work, management and capability building skills, with case study projects and…

Spatial Thinking Concepts in Early Grade-Level Geography Standards

ERIC Educational Resources Information Center

Anthamatten, Peter

2010-01-01

Research in the cognition and learning sciences has demonstrated that the human brain contains basic structures whose functions are to perform a variety of specific spatial reasoning tasks and that children are capable of learning basic spatial concepts at an early age. There has been a call from within geography to recognize research on spatial…

Stream Restoration as a Seminar Theme: Opportunities for Synthesis and Integration

ERIC Educational Resources Information Center

Moran, Sharon

2003-01-01

By using stream restoration as a seminar theme, geography faculty can create a topical course that helps provide a shared intellectual agenda for both physical and human geography students, while highlighting the holistic strengths of our discipline. Although it is not necessary that faculty have prior knowledge about the topic, a willingness to…

Emotions Matter: Teachers' Feelings about Their Interactions with Teacher Trainers during Curriculum Reform

ERIC Educational Resources Information Center

Yin, Hong-biao; Lee, John Chi-Kin

2011-01-01

Compared with the rich exploration of teachers' emotional geographies in the West, there have been only a small number of studies conducted in Chinese societies that have adopted Hargreaves's emotional geographies to analyze human interactions in education. This study explores the nature of emotions felt by teachers during their interactions with…

Teaching the Six Essential Elements of Geography with Quality Children's Literature

ERIC Educational Resources Information Center

Holloway, Jennifer

2015-01-01

In this article the author describes how she teaches third and sixth grade classes about the six essential elements of geography at the beginning of each school year. The six elements organize the eighteen national standards and include: the world in spatial terms, places and regions, physical systems, human systems, environment and society, and…

Workplace Preparedness for Terrorism

DTIC Science & Technology

2006-01-01

Geography Brand Points of Failure Human Continuity as Business Continuity Critical Event Preparedness Corporate-Community Cooperation and the...Public-Private Interface Training Cost Fear of Increasing Anxiety Geography : A corporation’s location, its corporate headquarters, its na- tional...incident team and include didactic and practical instruction. Th e opportunity to develop lessons learned from past or future disaster events can

Geomorphological Fieldwork

USGS Publications Warehouse

Thornbush, Mary J; Allen, Casey D; Fitzpatrick, Faith A.

2014-01-01

Geomorphological Fieldwork addresses a topic that always remains popular within the geosciences and environmental science. More specifically, the volume conveys a growing legacy of field-based learning for young geomorphologists that can be used as a student book for field-based university courses and postgraduate research requiring fieldwork or field schools. The editors have much experience of field-based learning within geomorphology and extend this to physical geography. The topics covered are relevant to basic geomorphology as well as applied approaches in environmental and cultural geomorphology. The book integrates a physical-human approach to geography, but focuses on physical geography and geomorphology from an integrated field-based geoscience perspective.

Unusual interaction of human apurinic/apyrimidinic endonuclease 1 (APE1) with abasic sites via the Schiff-base-dependent mechanism.

PubMed

Ilina, Ekaterina S; Khodyreva, Svetlana N; Lavrik, Olga I

2018-05-03

Clustered apurinic/apyrimidinic (AP) sites are more cytotoxic than isolated AP lesions because double strand breaks (DSB) can be formed during repair of closely positioned bistranded AP sites. Formation of DSB due to simultaneous cleavage of bistranded AP sites may be regulated by proteins specifically interacting with this complex lesion. A set of AP DNA duplexes containing AP sites in both strands in different mutual orientation (BS-AP DNAs) was used for search in the extracts of human cells proteins specifically recognizing clustered AP sites. A protein, which formed the Schiff-base-dependent covalent products having an apparent molecular mass of 50 kDa with the subset of BS-AP DNAs, was identified by mass spectrometry as apurinic/apyrimidinic endonuclease 1 (APE1). The identity of trapped protein was confirmed by Western blot analysis with anti-APE1 antibodies. Purified recombinant human APE1 is also capable of forming the 50 kDa-adducts with efficiency of BS-AP DNAs cross-linking to APE1 being dependent on the mutual orientation of AP sites. In spite of formation of the Schiff-base-dependent intermediate, which is prerequisite for the β-elimination mechanism, APE1 is unable to cleave AP sites. APE1 lacking the first 34 amino acids at the N-terminus, unlike wild type enzyme, is unable to form cross-links with BS-AP DNAs that testifies to the involvement of disordered N-terminal extension, which is enriched in lysine residues, in the interaction with AP sites. The yield of APE1-AP DNA cross-links was found to correlate with the enzyme amount in the extracts estimated by the immunochemical approach; therefore the BS-AP DNA-probes can be useful for comparative analysis of APE1 content in cell extracts. Copyright © 2018. Published by Elsevier B.V.

SARS coronavirus protein 7a interacts with human Ap4A-hydrolase.

PubMed

Vasilenko, Natalia; Moshynskyy, Igor; Zakhartchouk, Alexander

2010-02-09

The SARS coronavirus (SARS-CoV) open reading frame 7a (ORF 7a) encodes a 122 amino acid accessory protein. It has no significant sequence homology with any other known proteins. The 7a protein is present in the virus particle and has been shown to interact with several host proteins; thereby implicating it as being involved in several pathogenic processes including apoptosis, inhibition of cellular protein synthesis, and activation of p38 mitogen activated protein kinase. In this study we present data demonstrating that the SARS-CoV 7a protein interacts with human Ap4A-hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17). Ap4A-hydrolase is responsible for metabolizing the "allarmone" nucleotide Ap4A and therefore likely involved in regulation of cell proliferation, DNA replication, RNA processing, apoptosis and DNA repair. The interaction between 7a and Ap4A-hydrolase was identified using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation from cultured human cells transiently expressing V5-His tagged 7a and HA tagged Ap4A-hydrolase. Human tissue culture cells transiently expressing 7a and Ap4A-hydrolase tagged with EGFP and Ds-Red2 respectively show these proteins co-localize in the cytoplasm.

Ap4A induces apoptosis in human cultured cells.

PubMed

Vartanian, A; Alexandrov, I; Prudowski, I; McLennan, A; Kisselev, L

1999-07-30

Diadenosine oligophosphates (Ap(n)A) have been proposed as intracellular and extracellular signaling molecules in animal cells. The ratio of diadenosine 5',5'''-P1,P3-triphosphate to diadenosine 5',5'''-P1,P4-tetraphosphate (Ap3A/Ap4A) is sensitive to the cellular status and alters when cultured cells undergo differentiation or are treated with interferons. In cells undergoing apoptosis induced by DNA topoisomerase II inhibitor VP16, the concentration of Ap3A decreases significantly while that of Ap4A increases. Here, we have examined the effects of exogenously added Ap3A and Ap4A on apoptosis and morphological differentiation. Penetration of Ap(n)A into cells was achieved by cold shock. Ap4A at 10 microM induced programmed cell death in human HL60, U937 and Jurkat cells and mouse VMRO cells and this effect appeared to require Ap4A breakdown as hydrolysis-resistant analogues of Ap4A were inactive. On its own, Ap3A induced neither apoptosis nor cell differentiation but did display strong synergism with the protein kinase C activators 12-deoxyphorbol-13-O-phenylacetate and 12-deoxyphorbol-13-O-phenylacetate-20-acetate in inducing differentiation of HL60 cells. We propose that Ap4A and Ap3A are physiological antagonists in determination of the cellular status: Ap4A induces apoptosis whereas Ap3A is a co-inductor of differentiation. In both cases, the mechanism of signal transduction remains unknown.

The "Cultural Turn" in the Classroom: Two Examples of Pedagogy and the Politics of Representation

ERIC Educational Resources Information Center

Smith, Laurel

2002-01-01

This article offers video lessons that interweave visual and written materials in order to introduce university undergraduates (who may or may not be geography majors) to some recent shifts in geographic inquiry. What is often described as the "cultural turn" in human geography invites us to examine more closely the politics of representation,…

Lexington and Kentucky's Inner Bluegrass Region. Pathways in Geography Series, Site Guide Title No. 10.

ERIC Educational Resources Information Center

Ulack, Richard, Ed.; And Others

This meeting site guide for Lexington, Kentucky and the Bluegrass region around Lexington illustrates why the state of Kentucky and this region are excellent examples of how geography plays out on the land, how regions emerge, and how human events and processes, in the context of the physical environment, lead to differentiation and distinction,…

Plants and People: Vegetation Change in North America. Resource Publications in Geography.

ERIC Educational Resources Information Center

Vale, Thomas R.

General questions of vegetation change and the relationship between natural and human causes of plant disturbance are examined. The themes presented were treated by the author in a semester-long, college-level geography course. The book might be used as an outline for professors wishing to develop such a course, as a text for students, or as a…

Revisiting the Americas: Teaching and Learning the Geography of the Western Hemisphere. Pathways in Geography Series, Title No. 4.

ERIC Educational Resources Information Center

Martinson, Tom, Ed.; Brooker-Gross, Susan, Ed.

This book, issued in observance of the Columbus Quincentennial and on the occasion of the 27th International Geographical Congress, addresses a broad range of contemporary topics including environmental change, dynamics of the world economy, human needs, wants and rights, political order and change, and contemporary cultures. The format is one of…

Computational Framework for Analysis of Prey–Prey Associations in Interaction Proteomics Identifies Novel Human Protein–Protein Interactions and Networks

PubMed Central

Saha, Sudipto; Dazard, Jean-Eudes; Xu, Hua; Ewing, Rob M.

2013-01-01

Large-scale protein–protein interaction data sets have been generated for several species including yeast and human and have enabled the identification, quantification, and prediction of cellular molecular networks. Affinity purification-mass spectrometry (AP-MS) is the preeminent methodology for large-scale analysis of protein complexes, performed by immunopurifying a specific “bait” protein and its associated “prey” proteins. The analysis and interpretation of AP-MS data sets is, however, not straightforward. In addition, although yeast AP-MS data sets are relatively comprehensive, current human AP-MS data sets only sparsely cover the human interactome. Here we develop a framework for analysis of AP-MS data sets that addresses the issues of noise, missing data, and sparsity of coverage in the context of a current, real world human AP-MS data set. Our goal is to extend and increase the density of the known human interactome by integrating bait–prey and cocomplexed preys (prey–prey associations) into networks. Our framework incorporates a score for each identified protein, as well as elements of signal processing to improve the confidence of identified protein–protein interactions. We identify many protein networks enriched in known biological processes and functions. In addition, we show that integrated bait–prey and prey–prey interactions can be used to refine network topology and extend known protein networks. PMID:22845868

Pyridinylquinazolines Selectively Inhibit Human Methionine Aminopeptidase-1 in Cells

PubMed Central

Zhang, Feiran; Bhat, Shridhar; Gabelli, Sandra B.; Chen, Xiaochun; Miller, Michelle S.; Nacev, Benjamin A.; Cheng, Yim Ling; Meyers, David J.; Tenney, Karen; Shim, Joong Sup; Crews, Phillip; Amzel, L. Mario; Ma, Dawei; Liu, Jun O.

2013-01-01

Methionine aminopeptidases (MetAPs) which remove the initiator methionine from nascent peptides are essential in all organisms. While MetAP2 has been demonstrated to be a therapeutic target for inhibiting angiogenesis in mammals, MetAP1 seems to be vital for cell proliferation. Our earlier efforts identified two structural classes of human MetAP1 (HsMetAP1)-selective inhibitors (1–4). But all of them failed to inhibit cellular HsMetAP1. Using Mn(II) or Zn(II) to activate HsMetAP1, we found that 1–4 could only effectively inhibit purified HsMetAP1 in the presence of physiologically unachievable concentrations of Co(II). In an effort to seek Co(II)-independent inhibitors, a novel structural class containing a 2-(pyridin-2-yl)quinazoline core has been discovered. Many compounds in this class potently and selectively inhibited HsMetAP1 without Co(II). Subsequently, we demonstrated that 11j, an auxiliary metal-dependent inhibitor, effectively inhibited HsMetAP1 in primary cells. This is the first report that an HsMetAP1-selective inhibitor is effective against its target in cells. PMID:23634668

Complement-mediated opsonization of invasive group A Streptococcus pyogenes strain AP53 is regulated by the bacterial two-component cluster of virulence responder/sensor (CovRS) system.

PubMed

Agrahari, Garima; Liang, Zhong; Mayfield, Jeffrey A; Balsara, Rashna D; Ploplis, Victoria A; Castellino, Francis J

2013-09-20

Group A Streptococcus pyogenes (GAS) strain AP53 is a primary isolate from a patient with necrotizing fasciitis. These AP53 cells contain an inactivating mutation in the sensor component of the cluster of virulence (cov) responder (R)/sensor (S) two-component gene regulatory system (covRS), which enhances the virulence of the primary strain, AP53/covR(+)S(-). However, specific mechanisms by which the covRS system regulates the survival of GAS in humans are incomplete. Here, we show a key role for covRS in the regulation of opsonophagocytosis of AP53 by human neutrophils. AP53/covR(+)S(-) cells displayed potent binding of host complement inhibitors of C3 convertase, viz. Factor H (FH) and C4-binding protein (C4BP), which concomitantly led to minimal C3b deposition on AP53 cells, further showing that these plasma protein inhibitors are active on GAS cells. This resulted in weak killing of the bacteria by human neutrophils and a corresponding high death rate of mice after injection of these cells. After targeted allelic alteration of covS(-) to wild-type covS (covS(+)), a dramatic loss of FH and C4BP binding to the AP53/covR(+)S(+) cells was observed. This resulted in elevated C3b deposition on AP53/covR(+)S(+) cells, a high level of opsonophagocytosis by human neutrophils, and a very low death rate of mice infected with AP53/covR(+)S(+). We show that covRS is a critical transcriptional regulator of genes directing AP53 killing by neutrophils and regulates the levels of the receptors for FH and C4BP, which we identify as the products of the fba and enn genes, respectively.

Human recombinant alkaline phosphatase inhibits ex vivo platelet activation in humans.

PubMed

Tunjungputri, Rahajeng N; Peters, Esther; van der Ven, André; de Groot, Philip G; de Mast, Quirijn; Pickkers, Peter

2016-11-30

Sepsis-associated acute kidney injury (AKI) is associated with high morbidity and mortality. Excessive platelet activation contributes to AKI through the formation of microthrombi and amplification of systemic inflammation. Two phase II trials demonstrated that bovine-intestinal alkaline phosphatase (AP) improved renal function in critically ill patients with sepsis-associated AKI. In this study, we characterised the platelet-inhibiting effects of a human recombinant AP. Whole blood and platelet-rich plasma (PRP) of healthy volunteers (n=6) was pre-treated ex vivo with recAP, whereafter platelet reactivity to ADP, collagen-related peptide (CRP-XL) and Pam3CSK4 was determined by flow cytometry. RecAP (40 U/ml) reduced the platelet reactivity to ADP (inhibition with a median of 47 %, interquartile range 43-49 %; p<0.001) and tended to reduce platelet reactivity to CRP-XL (9 %, 2-25 %; p=0.08) in whole blood. The platelet-inhibiting effects of recAP were more pronounced in PRP both for ADP- (64 %, 54-68 %; p=0.002) and CRP-XL-stimulated samples (60 %, 46-71 %; p=0.002). RecAP rapidly converted ADP into adenosine, whereas antagonism of the A2A adenosine receptor partially reversed the platelet inhibitory effects of recAP. Platelets of septic shock patients (n=5) showed a 31% (22-34%; p=0.03) more pronounced reactivity compared to healthy volunteers, and this was completely reversed by recAP treatment. In conclusion, we demonstrate that recAP inhibits ex vivo human platelet activation through dephosphorylation of ADP and formation of adenosine as its turnover product. RecAP is able to reverse the platelet hyperreactivity present in septic shock patients. These effects may contribute to the beneficial effects of recAP as a new therapeutic candidate for sepsis-associated AKI.

Crystal structure of wild-type and mutant human Ap4A hydrolase.

PubMed

Ge, Honghua; Chen, Xiaofang; Yang, Weili; Niu, Liwen; Teng, Maikun

2013-03-01

Ap4A hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17), an enzyme involved in a number of biological processes, is characterized as cleaving the polyphosphate chain at the fourth phosphate from the bound adenosine moiety. This paper presents the crystal structure of wild-type and E58A mutant human Ap4A hydrolase. Similar to the canonical Nudix fold, human Ap4A hydrolase shows the common αβα-sandwich architecture. Interestingly, two sulfate ions and one diphosphate coordinated with some conserved residues were observed in the active cleft, which affords a better understanding of a possible mode of substrate binding. Copyright © 2013 Elsevier Inc. All rights reserved.

A putative marker for human pathogenic strains of Anaplasma phagocytophilum correlates with geography and host, but not human tropism.

PubMed

Foley, Janet; Stephenson, Nicole; Cubilla, Michelle Pires; Qurollo, Barbara; Breitschwerdt, Edward B

2016-03-01

Anaplasma phagocytophilum is an Ixodes species tick-transmitted bacterium that is capable of infecting a variety of host species, although there is a diversity of bacterial strains with differing host tropism. Recent analysis of A. phagocytophilum strains suggested that "drhm", a gene locus designated "distantly related to human marker" (drhm), which was predicted to be an integral membrane protein with possible transporter functions was not present in available canine and human isolates. By assessing 117 strains from 14 host species from across the US, we extended this analysis. Phylogenetic clades were associated with geography, but not host species. Additionally, a virulent clade that lacks drhm and infects dogs, horses, and humans in northeastern US was identified. Copyright © 2015 Elsevier GmbH. All rights reserved.

The Functionality of a Geography Information System (GIS) Technology in Geography Teaching: Application of a Sample Lesson

ERIC Educational Resources Information Center

Ozgen, Nurettin

2009-01-01

A Geographic Information System (GIS) is a high performance computer-aided chain of software which enables us to understand, interpret, capture, update, map, and display natural and human-originated events on Earth and allows us to bring out such phenomena in a form of synthesis. Therefore, a GIS is an important information system in which…

Ability of circulating human hematopoietic lineage negative cells to support hematopoiesis.

PubMed

Peris, Pilar; Roforth, Matthew M; Nicks, Kristy M; Fraser, Daniel; Fujita, Koji; Jilka, Robert L; Khosla, Sundeep; McGregor, Ulrike

2015-01-01

Hematopoietic stem cell (HSC) self-renewal is regulated by osteoblast and/or endothelial cells within the hematopoietic niche. However, the true identity of the supporting cells and the nature of the secreted factors remain uncertain. We developed a novel mouse model and analyzed whether circulating human peripheral hematopoietic lineage negative/AP+ (lin-/AP+) cells support hematopoiesis in vivo. Thus, immunocompromised (Rag) mice expressing thymidine kinase (Tk) under the control of the 3.6Col1α1 promoter (Tk-Rag) were treated with ganciclovir, resulting in osteoblast progenitor cell ablation and subsequent loss of hematopoiesis (evaluated by measuring mouse Ter119+ erythroid cells). Following hematopoietic cell depletion, human bone marrow-derived marrow stromal cells (MSCs) or lin-/AP+ cells were infused into Tk-Rag mice and compared with saline infusions. Ganciclovir significantly reduced (7.4-fold) Ter119+ cells in the bone marrow of Tk-Rag mice compared to saline injections. Infusion of either MSCs or lin-/AP+ cells into ganciclovir-treated mice resulted in a 3.3-fold and 2.7-fold increase (P < 0.01), respectively, in Ter119+ cells compared to mice receiving saline. Relative to lin-/AP- cells, lin-/AP+ cells expressed high levels of mesenchymal, endothelial, and hematopoiesis supporting genes. Thus, human peripheral blood lin-/AP+ cells represent a novel cell type capable of supporting hematopoiesis in a manner comparable to MSCs. © 2014 Wiley Periodicals, Inc.

AP Music Theory Applied

ERIC Educational Resources Information Center

Spieker, Matthew H.

2016-01-01

Some American high schools include Advanced Placement (AP) Music Theory within their course offerings. Students who pass the AP exam can receive college credit either as a music or humanities credit. An AP class, however, offers music students more than future college credit; it ultimately improves musicianship skills and promotes deeper…

Characterization of a diadenosine tetraphosphate-receptor distinct from the ATP-purinoceptor in human tracheal gland cells.

PubMed

Saleh, A; Picher, M; Kammouni, W; Figarella, C; Merten, M D

1999-11-12

Human submucosal tracheal glands are now believed to play a major role in the physiopathology of cystic fibrosis, a genetic disease in which ATP is used as a therapeutic agent. However, actions of ATP on tracheal gland cells are not well known. ATP binds to P2 receptors and induced secretory leucocyte protease inhibitor (SLPI) secretion through formation of cyclic adenosine monophosphate and mobilization of intracellular [Ca(2+)]. Since diadenosine polyphosphates (ApnA) are also endogenous effectors of P2 receptors, we investigated their effects in a cell line (MM39) of human tracheal gland cells. Diadenosine tetraphosphates (Ap4A) induced significant stimulation (+50+/-12%) of SLPI secretion and to a similar extent to that of ATP (+65+/-10%). No significant effects were observed with diadenosine triphosphate (Ap3A), diadenosine pentaphosphate (Ap5A), ADP and 2-methylthio-adenosine triphosphate (2-MeS-ATP). Since Ap4A was weakly hydrolyzed (<2% of total), and the hydrolysis product was only inosine which is ineffective on cells, this Ap4A effect was not due to Ap4A hydrolysis in ATP and adenosine monophosphate (AMP). A mixture of Ap4A and ATP elicited only partial additive effects on SLPI secretion. ADP was shown to be a potent antagonist of ATP and Ap4A receptors, with IC(50)s of 0.8 and 2 microM, respectively. 2-MeS-ATP also showed antagonistic properties with IC(50)s of 20 and 30 microM for ATP- and Ap4A-receptors, respectively. Single cell intracellular calcium ([Ca(2+)](i)) measurements showed similar transient increases of [Ca(2+)](i) after ATP or Ap4A challenges. ATP desensitized the cell [Ca(2+)](i) responses to ATP and Ap4A, and Ap4A also desensitized the cell response to Ap4A. Nevertheless, Ap4A did not desensitize the cell [Ca(2+)](i) responses to ATP. In conclusion, both P2Y2-ATP-receptors and Ap4A-P2D-receptors seem to be present in tracheal gland cells. Ap4A may only bind to P2D-receptors whilst ATP may bind to both Ap4A- and ATP-receptors.

Inositol-1,4,5-trisphosphate increase by diadenosine tetraphosphate in preparations from failing human myocardium.

PubMed

Knapp, J; Bokník, P; Linck, B; Läer, S; Müller, F U; Neumann, J; Vahlensieck, U; Schlüter, H; Zidek, W; Schmitz, W

1999-09-01

In human ventricular trabeculae carneae 100 microM AP4A (diadenosine tetraphosphate) increased force of contraction to 162.8+/-15.7% of predrug value (n=9). This positive inotropic effect was accompanied by a prolongation of time parameters: time to peak tension and time of relaxation were prolonged by 7.8+/-1.3% and 14.9+/-3.8%, respectively (P<0.05). In the same trabeculae, AP4A increased IP3 (inositol-1,4,5-trisphosphate) content from 9.0+/-1.3 pmol/mg to 22.9+/-5.4 pmol/mg protein (n=5-9). In conclusion, the positive inotropic effect of AP4A in the human myocardium is likely due to an increase of IP3 mediated probably via Gq-coupled P2Y-purinoceptors. Because of the prominent role of Gq in the development of cardiac disease, these findings may lay the ground to further investigate the possible role of AP4A and/or related ligands (e.g. AP2A and AP3A) in heart failure.

Following rules in the intermontane west: 19th-century mormon settlement

PubMed Central

Norton, William

2001-01-01

The academic discipline of human geography is concerned with human activities, especially as these relate to physical landscapes and contribute to the modification of those landscapes. Although little attention has been paid to objectivist philosophies to inform human geography, behavior analysis might offer a useful explanatory model. As an example, a behavior analysis of selected aspects of 19th-century Mormon movement and settlement in the intermontane West is conducted. Mormons are a society of believers who practice cooperative effort and support for other members, and the Mormon church is governed by priesthood authority with members being called to perform tasks. This analysis employs the concepts of metacontingency, rule-governed behavior, and delayed reinforcement to analyze how Mormons settled the intermontane West. PMID:22478355

Spatial Relations and the Struggle for Space: Friedrich Ratzel's Impact on German Education from the Wilhelmine Empire to the Third Reich

ERIC Educational Resources Information Center

Paddock, Troy

2016-01-01

This article examines the influence of Friedrich Ratzel's idea of the struggle for space and its impact on cultural and national development depicted in German geography and history textbooks from the Wilhelmine era to the Third Reich. Ratzel's concept of bio-geography conceived the state as a living organism that is the product of humanity's…

Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation

PubMed Central

Durgampudi, Chandra; Noel, Pawan; Patel, Krutika; Cline, Rachel; Trivedi, Ram N.; DeLany, James P.; Yadav, Dhiraj; Papachristou, Georgios I.; Lee, Kenneth; Acharya, Chathur; Jaligama, Deepthi; Navina, Sarah; Murad, Faris; Singh, Vijay P.

2015-01-01

Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O–positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate–induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction. PMID:24854864

Crystal structures and biochemical analyses suggest a unique mechanism and role for human glycyl-tRNA synthetase in Ap4A homeostasis.

PubMed

Guo, Rey-Ting; Chong, Yeeting E; Guo, Min; Yang, Xiang-Lei

2009-10-16

Aminoacyl-tRNA synthetases catalyze the attachment of amino acids to their cognate tRNAs for protein synthesis. However, the aminoacylation reaction can be diverted to produce diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways. The only known mechanism for Ap4A production by a tRNA synthetase is through the aminoacylation reaction intermediate aminoacyl-AMP, thus making Ap4A synthesis amino acid-dependent. Here, we demonstrate a new mechanism for Ap4A synthesis. Crystal structures and biochemical analyses show that human glycyl-tRNA synthetase (GlyRS) produces Ap4A by direct condensation of two ATPs, independent of glycine concentration. Interestingly, whereas the first ATP-binding pocket is conserved for all class II tRNA synthetases, the second ATP pocket is formed by an insertion domain that is unique to GlyRS, suggesting that GlyRS is the only tRNA synthetase catalyzing direct Ap4A synthesis. A special role for GlyRS in Ap4A homeostasis is proposed.

Crystal Structures and Biochemical Analyses Suggest a Unique Mechanism and Role for Human Glycyl-tRNA Synthetase in Ap4A Homeostasis*

PubMed Central

Guo, Rey-Ting; Chong, Yeeting E.; Guo, Min; Yang, Xiang-Lei

2009-01-01

Aminoacyl-tRNA synthetases catalyze the attachment of amino acids to their cognate tRNAs for protein synthesis. However, the aminoacylation reaction can be diverted to produce diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways. The only known mechanism for Ap4A production by a tRNA synthetase is through the aminoacylation reaction intermediate aminoacyl-AMP, thus making Ap4A synthesis amino acid-dependent. Here, we demonstrate a new mechanism for Ap4A synthesis. Crystal structures and biochemical analyses show that human glycyl-tRNA synthetase (GlyRS) produces Ap4A by direct condensation of two ATPs, independent of glycine concentration. Interestingly, whereas the first ATP-binding pocket is conserved for all class II tRNA synthetases, the second ATP pocket is formed by an insertion domain that is unique to GlyRS, suggesting that GlyRS is the only tRNA synthetase catalyzing direct Ap4A synthesis. A special role for GlyRS in Ap4A homeostasis is proposed. PMID:19710017

Effects of a human recombinant alkaline phosphatase on renal hemodynamics, oxygenation and inflammation in two models of acute kidney injury

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

Peters, Esther, E-mail: esther.peters@radboudumc.n

Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase (AP) improves renal function in critically ill patients with sepsis-associated acute kidney injury (AKI), for which the mechanism of action is not completely understood. Here, we investigated the effects of a newly developed human recombinant AP (recAP) on renal oxygenation and hemodynamics and prevention of kidney damage and inflammation in two in vivo AKI models. To induce AKI, male Wistar rats (n = 18) were subjected to renal ischemia (30 min) and reperfusion (I/R), or sham-operated. In a second model, rats (n = 18) received a 30 minmore » infusion of lipopolysaccharide (LPS; 2.5 mg/kg), or saline, and fluid resuscitation. In both models, recAP (1000 U/kg) was administered intravenously (15 min before reperfusion, or 90 min after LPS). Following recAP treatment, I/R-induced changes in renal blood flow, renal vascular resistance and oxygen delivery at early, and cortical microvascular oxygen tension at late reperfusion were no longer significantly affected. RecAP did not influence I/R-induced effects on mean arterial pressure. During endotoxemia, recAP treatment did not modulate the LPS-induced changes in systemic hemodynamics and renal oxygenation. In both models, recAP did exert a clear renal protective anti-inflammatory effect, demonstrated by attenuated immunostaining of inflammatory, tubular injury and pro-apoptosis markers. Whether this renal protective effect is sufficient to improve outcome of patients suffering from sepsis-associated AKI is being investigated in a large clinical trial. - Highlights: • Human recombinant alkaline phosphatase (recAP) is a potential new therapy for sepsis-associated acute kidney injury (AKI). • RecAP can modulate renal oxygenation and hemodynamics immediately following I/R-induced AKI. • RecAP did not modulate endotoxemia-induced changes in systemic hemodynamics and renal oxygenation. • RecAP did exert a clear renal protective anti-inflammatory effect in both models.« less

Geography as Human Ecology: A Decade of Progress in a Quarter Century

ERIC Educational Resources Information Center

Porter, Philip W.

1978-01-01

Traces advances in human ecology from 1954-1978, considers research methodology used by geographers to study human ecology, and summarizes major research findings. Concludes that geographers should develop models to explain mutual relations of people and environment. (Author/DB)

Glaucoma patients present increased levels of diadenosine tetraphosphate, Ap(4)A, in the aqueous humour.

PubMed

Castany, Marta; Jordi, Isabel; Catala, Jaume; Gual, Arcadi; Morales, Miguel; Gasull, Xavier; Pintor, Jesus

2011-03-01

Previous studies have shown the presence of diadenosine tetraphosphate (Ap(4)A) and pentaphosphate (Ap(5)A) in the aqueous humour (AH) of different species. When topically applied to the rabbit cornea, Ap(4)A decreased IOP while Ap(5)A increased it. Here we study the presence of dinucleoside polyphosphates in the AH from human patients with or without glaucoma. AH was obtained at the time of cataract surgery from patients with (n=16) or without (n=10) primary open-angle glaucoma. AH (0.1-0.2 ml) was collected at the beginning of surgery through a corneal paracentesis and immediately cooled in liquid nitrogen, kept frozen and protected from light. AH aliquots were analyzed by HPLC for the presence of Ap(4)A and Ap(5)A. Both, Ap(4)A and Ap(5)A were detected in the AH of both experimental groups. No significant differences were found for Ap(5)A. In contrast, Ap(4)A levels were increased by ∼15-fold in the AH from glaucomatous eyes ranging from 19.5±9.2 nM in normal individuals to 286.03±30.9 nM in glaucomatous patients. In conclusion, both Ap(4)A and Ap(5)A were detected for the first time in human AH. Interestingly, glaucomatous eyes presented elevated concentrations of Ap(4)A compared to controls. The role of Ap(4)A needs to be elucidated but it may help to protect the autonomic innervation in the ciliary body/trabecular meshwork. Also, because of its higher levels in glaucoma patients it may be considered as a possible glaucoma biomarker. Copyright © 2010 Elsevier Ltd. All rights reserved.

Ecto-diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A)-hydrolase is expressed as an ectoenzyme in a variety of mammalian and human cells and adds new aspects to the turnover of Ap4A.

PubMed

von Drygalski, A; Ogilvie, A

2000-01-01

Ap4A and other dinucleotides participate in the regulation of hemostasis and blood pressure control. With the exception of two previously reported surface anchored ectoAp4A-hydrolases on bovine aortic endothelial and chromaffine cells, all Ap4A-hydrolases reported are intracellular or freely soluble. We demonstrated that ectoAp4A-hydrolases are present on a broad variety of cell types of different species: rat mesangial, bovine corneal epithelial, human Hep-G2 and peridontal cells. Ectoenzyme properties were evaluated on rat mesangium cells. Chromatography of purified plasma membranes on Sephacel 300 resulted in enrichment of ectoAp4A-hydrolase and in separation from ectoATPase. In contrast to ATPase, Ap4A-hydrolase was stable at room temperature. EctoAp4A-hydrolase also recognized ATP as substrate, and therefore is not highly specific. The molecular weight was 180 kD. Unlike ectoAMPase ectoAp4A-hydrolase was not attached via a glycosyl-phosphatidylinositol (GPI)-moiety. Concentrations of PI-PLC 10-100-fold higher than effective for ectoAMPase cleavage (10-100 mU/ml) plus extensively extended incubation times up to eight hours did not result in cleavage of ectoAp4A-hydrolase. The enzyme ectoAp4A-hydrolase might presage a direction for pharmaceutical manipulation in the control of blood pressure and hemostasis.

Human gut microbiome viewed across age and geography

USDA-ARS?s Scientific Manuscript database

Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, we characterized bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy child...

'The medical' and 'health' in a critical medical humanities.

PubMed

Atkinson, Sarah; Evans, Bethan; Woods, Angela; Kearns, Robin

2015-03-01

As befits an emerging field of enquiry, there is on-going discussion about the scope, role and future of the medical humanities. One relatively recent contribution to this debate proposes a differentiation of the field into two distinct terrains, 'medical humanities' and 'health humanities,' and calls for a supersession of the former by the latter. In this paper, we revisit the conceptual underpinnings for a distinction between 'the medical' and 'health' by looking at the history of an analogous debate between 'medical geography' and 'the geographies of health' that has, over the last few years, witnessed a re-blurring of the distinction. Highlighting the value of this debate within the social sciences for the future development of the medical humanities, we call for scholars to take seriously the challenges of critical and cultural theory, community-based arts and health, and the counter-cultural creative practices and strategies of activist movements in order to meet the new research challenges and fulfill the radical potential of a critical medical humanities.

Optimization of Extracellular Matrix Synthesis and Accumulation by Human Articular Chondrocytes in 3-Dimensional Construct with Repetitive Hydrostatic Pressure.

PubMed

Ogura, Takahiro; Tsuchiya, Akihiro; Minas, Tom; Mizuno, Shuichi

2018-04-01

Objective The effects of hydrostatic pressure (HP) on the matrix synthesis by human articular chondrocytes have been reported elsewhere. In order to optimize the production of extracellular matrix, we aimed to clarify the effects of repetitive HP on metabolic function by human articular chondrocytes. Design The human articular chondrocytes were expanded and embedded within a collagen gel/sponge scaffold. We incubated these constructs with and without HP followed by atmospheric pressure (AP) and repeated the second HP followed by AP over 14 days. Genomic, biochemical, and histological evaluation were performed to compare the effects of each regimen on the constructs. Results The gene expressions of collagen type II and aggrecan core protein were significantly upregulated with repetitive HP regimens compared with a single HP or AP by 14 days ( P < 0.01 or 0.05). Matrix metalloptoteinase-13 (MMP-13) in AP was upregulated significantly compared to other HP regimens at day 14 ( P < 0.01). No significant difference was observed in tissue inhibitor of metalloproteinases-II. Immunohistology demonstrated that application of HP (both repetitive and single) promoted the accumulation of specific extracellular matrix and reduced a MMP-13. A single regimen of HP followed by AP significantly increased the amount of sulfated glycosaminoglycan than that of the AP, whereas repetitive HP remained similar level of that of the AP. Conclusions Repetitive HP had a greater effect on anabolic activity by chondrocytes than a single HP regimen, which will be advantageous for producing a matrix-rich cell construct.

Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of human AP endonuclease 1

PubMed Central

Malina, Jaroslav; Scott, Peter; Brabec, Viktor

2015-01-01

Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo–helical ‘flexicate’ complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3]4+ incorporating the common NN–NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo–helical complexes for cancer chemotherapy. PMID:25940617

AP1S3 mutations are associated with pustular psoriasis and impaired Toll-like receptor 3 trafficking.

PubMed

Setta-Kaffetzi, Niovi; Simpson, Michael A; Navarini, Alexander A; Patel, Varsha M; Lu, Hui-Chun; Allen, Michael H; Duckworth, Michael; Bachelez, Hervé; Burden, A David; Choon, Siew-Eng; Griffiths, Christopher E M; Kirby, Brian; Kolios, Antonios; Seyger, Marieke M B; Prins, Christa; Smahi, Asma; Trembath, Richard C; Fraternali, Franca; Smith, Catherine H; Barker, Jonathan N; Capon, Francesca

2014-05-01

Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Antiviral activity of acidic polysaccharides from Coccomyxa gloeobotrydiformi, a green alga, against an in vitro human influenza A virus infection.

PubMed

Komatsu, Takayuki; Kido, Nobuo; Sugiyama, Tsuyoshi; Yokochi, Takashi

2013-02-01

The extracts prepared from green algae are reported to possess a variety of biological activities including antioxidant, antitumor and antiviral activities. The acidic polysaccharide fraction from a green alga Coccomyxa gloeobotrydiformi (CmAPS) was isolated and the antiviral action on an in vitro infection of influenza A virus was examined. CmAPS inhibited the growth and yield of all influenza A virus strains tested, such as A/H1N1, A/H2N2, A/H3N2 and A/H1N1 pandemic strains. The 50% inhibitory concentration of CmAPS on the infection of human influenza A virus strains ranged from 26 to 70 µg/mL and the antiviral activity of CmAPS against influenza A/USSR90/77 (H1N1) was the strongest. The antiviral activity of CmAPS was not due to the cytotoxicity against host cells. The antiviral activity of CmAPS required its presence in the inoculation of virus onto MDCK cells. Pretreatment and post-treatment with CmAPS was ineffective for the antiviral activity. CmAPS inhibited influenza A virus-induced erythrocyte hemagglutination and hemolysis. Taken together, CmAPS was suggested to exhibit the anti-influenza virus activity through preventing the interaction of virus and host cells. The detailed antiviral activity of CmAPS is discussed.

Promotion of Homologous Recombination and Genomic Stability byRAD51AP1 via RAD51 Recombinase Enhancement

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

Wiese, Claudia; Dray, Eloise; Groesser, Torsten

2007-04-11

Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand pairing step in HR. RAD51AP1 (RAD51 Associated Protein 1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA damaging treatment. Purified RAD51AP1 binds dsDNA and RAD51, and it greatly stimulates the RAD51-mediated D-loop reaction. Biochemical and cytological results show that RAD51AP1more » functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide the first evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.« less

Geography in School and a Curriculum of Survival

ERIC Educational Resources Information Center

Lambert, David

2013-01-01

The economic and environmental crises that face humanity today require an educational response. This article accepts the proposition that education may play a part in preparing human beings to survive impacts of human-induced climate change for example. However, education, according to some conceptualizations, is also in crisis. It therefore…

Wandering Minds: Tracing Inner Worlds Through a Historical-Geographical Art Installation

PubMed Central

Powell, Hilary; Morrison, Hazel; Callard, Felicity

2018-01-01

The human act of wandering across landscapes and cityscapes has carved the research interests of scholars in cultural, urban, and historical geography, as well as in the humanities. Here we call for—and take the first steps toward—a historical geography of wandering that is pursued in the head rather than with the legs. We do so through analyzing how our audiovisual installation on mind wandering opened up epistemological and ontological questions facing historical geographies of the mind. This installation both modeled mind wandering as conceptualized at different historical moments and aimed to induce mental perambulation in its visitors. In so doing, it was intended both to stage and to disrupt relations between body and mind, the internal and external, attention and inattention, motion and stillness—and, importantly, between the archival and that which resists archival capture. We reflect on how we interspersed traditional scholarly historical and geographical enquiry with methods gleaned from creative practices. In particular, we consider the challenges that such practices pose for how we conceptualize archives—not least when the focus of attention comprises fugitive mental phenomena.

Inhibitory function of adapter-related protein complex 2 alpha 1 subunit in the process of nuclear translocation of human immunodeficiency virus type 1 genome

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

Kitagawa, Yukiko; Department of Oral and Maxillofacial Surgery II, Osaka University, Osaka 565-0871; Kameoka, Masanori

2008-03-30

The transfection of human cells with siRNA against adapter-related protein complex 2 alpha 1 subunit (AP2{alpha}) was revealed to significantly up-regulate the replication of human immunodeficiency virus type 1 (HIV-1). This effect was confirmed by cell infection with vesicular stomatitis virus G protein-pseudotyped HIV-1 as well as CXCR4-tropic and CCR5-tropic HIV-1. Viral adsorption, viral entry and reverse transcription processes were not affected by cell transfection with siRNA against AP2{alpha}. In contrast, viral nuclear translocation as well as the integration process was significantly up-regulated in cells transfected with siRNA against AP2{alpha}. Confocal fluorescence microscopy revealed that a subpopulation of AP2{alpha} wasmore » not only localized in the cytoplasm but was also partly co-localized with lamin B, importin {beta} and Nup153, implying that AP2{alpha} negatively regulates HIV-1 replication in the process of nuclear translocation of viral DNA in the cytoplasm or the perinuclear region. We propose that AP2{alpha} may be a novel target for disrupting HIV-1 replication in the early stage of the viral life cycle.« less

Solution NMR structures of homeodomains from human proteins ALX4, ZHX1, and CASP8AP2 contribute to the structural coverage of the Human Cancer Protein Interaction Network.

PubMed

Xu, Xianzhong; Pulavarti, Surya V S R K; Eletsky, Alexander; Huang, Yuanpeng Janet; Acton, Thomas B; Xiao, Rong; Everett, John K; Montelione, Gaetano T; Szyperski, Thomas

2014-12-01

High-quality solution NMR structures of three homeodomains from human proteins ALX4, ZHX1 and CASP8AP2 were solved. These domains were chosen as targets of a biomedical theme project pursued by the Northeast Structural Genomics Consortium. This project focuses on increasing the structural coverage of human proteins associated with cancer.

DIFFERENTIAL ACTIVATION OF AP-1 IN HUMAN BLADDER EPITHELIAL CELLS BY INORGANIC AND METHYLATED ARSENICALS

EPA Science Inventory

Differential Activation of AP-1 in Human Bladder Epithelial Cells by Inorganic and Methylated Arsenicals

Zuzana Drobna, Ilona Jaspers, David J. Thomas, and Miroslav Styblo

ABSTRACT

Epidemiological studies have linked chronic ingestion of drinking water contai...

Kinase activation through dimerization by human SH2-B.

PubMed

Nishi, Masahiro; Werner, Eric D; Oh, Byung-Chul; Frantz, J Daniel; Dhe-Paganon, Sirano; Hansen, Lone; Lee, Jongsoon; Shoelson, Steven E

2005-04-01

The isoforms of SH2-B, APS, and Lnk form a family of signaling proteins that have been described as activators, mediators, or inhibitors of cytokine and growth factor signaling. We now show that the three alternatively spliced isoforms of human SH2-B readily homodimerize in yeast two-hybrid and cellular transfections assays, and this is mediated specifically by a unique domain in its amino terminus. Consistent with previous reports, we further show that the SH2 domains of SH2-B and APS bind JAK2 at Tyr813. These findings suggested a model in which two molecules of SH2-B or APS homodimerize with their SH2 domains bound to two JAK2 molecules, creating heterotetrameric JAK2-(SH2-B)2-JAK2 or JAK2-(APS)2-JAK2 complexes. We further show that APS and SH2-B isoforms heterodimerize. At lower levels of SH2-B or APS expression, dimerization approximates two JAK2 molecules to induce transactivation. At higher relative concentrations of SH2-B or APS, kinase activation is blocked. SH2-B or APS homodimerization and SH2-B/APS heterodimerization thus provide direct mechanisms for activating and inhibiting JAK2 and other kinases from the inside of the cell and for potentiating or attenuating cytokine and growth factor receptor signaling when ligands are present.

Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of human AP endonuclease 1.

PubMed

Malina, Jaroslav; Scott, Peter; Brabec, Viktor

2015-06-23

Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo-helical 'flexicate' complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3](4+) incorporating the common NN-NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo-helical complexes for cancer chemotherapy. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis

PubMed Central

Lu, Duo; Silhan, Jan; MacDonald, James T.; Carpenter, Elisabeth P.; Jensen, Kirsten; Tang, Christoph M.; Baldwin, Geoff S.; Freemont, Paul S.

2012-01-01

Base excision repair (BER) is a highly conserved DNA repair pathway throughout all kingdoms from bacteria to humans. Whereas several enzymes are required to complete the multistep repair process of damaged bases, apurinic-apyrimidic (AP) endonucleases play an essential role in enabling the repair process by recognizing intermediary abasic sites cleaving the phosphodiester backbone 5′ to the abasic site. Despite extensive study, there is no structure of a bacterial AP endonuclease bound to substrate DNA. Furthermore, the structural mechanism for AP-site cleavage is incomplete. Here we report a detailed structural and biochemical study of the AP endonuclease from Neisseria meningitidis that has allowed us to capture structural intermediates providing more complete snapshots of the catalytic mechanism. Our data reveal subtle differences in AP-site recognition and kinetics between the human and bacterial enzymes that may reflect different evolutionary pressures. PMID:23035246

Expression of the GM2 activator protein in mouse testis.

PubMed

Li, Yu-Teh; Li, Su-Chen; Chen, I-Li

2017-12-01

The GM2-activator protein (GM2-AP), revealed by Li et al. in 1973 in human liver, was initially identified as a protein cofactor that stimulated β-hexosaminidase A to hydrolyze N-acetylgalactosamine from GM2 ganglioside. This cofactor was found to be missing in human variant AB Tay-Sachs disease. Over the years, the GM2-AP has also been shown to be involved in kidney vesicular transport, lipid presentation by CD1 molecule to T-cells, and interaction of human sperm with zona pellucida. Since the expression of the GM2-AP via mRNA detection in mouse tissues was found to be the highest in testis, we became interested in the localization of the GM2-AP at cellular level in mouse testis during spermatogenesis. Using immunohistochemical analysis and electron microscopy, we found that the GM2-AP was predominantly localized in the basal cytoplasm and the attenuated processes of Sertoli cells. The stained structure appeared to be lysosomes. The most interesting finding was the association of the GM2-AP with the acrosomal apparatus in early spermatids. A modest to intense staining was observed in some acrosomal granules and acrosomal caps. The GM2-AP seemed to disappear from acrosomal caps in the later stage of spermatids, in which the nucleus became elongated and condensed. These results suggest that the GM2-AP may be involved in the normal functions of Sertoli cells and play important roles during the development of acrosomal caps in the early spermatids. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

High Quality in Primary Humanities: Insights from the UK's School Inspectorates

ERIC Educational Resources Information Center

Catling, Simon

2017-01-01

The school inspectorates of the four jurisdictions of the UK are sources of evidence about the quality of humanities teaching, learning and curriculum in primary schools. The term "humanities" usually refers to the subjects of geography, history and Religious Education, but here they are considered holistically, not separately. Discrete…

*Assessing differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles

EPA Science Inventory

Background: Exposure to Diesel Exhaust Particles (DEP) induces inflammatory signaling characterized by MAP kinase-mediated activation of NFkB and AP-l in vitro and in bronchial biopsies obtained from human subjects exposed to DEP. NFkB and AP-l activation results in the upregulat...

KITENIN is associated with tumor progression in human gastric cancer.

PubMed

Ryu, Ho-Seong; Park, Young-Lan; Park, Su-Jin; Lee, Ji-Hee; Cho, Sung-Bum; Lee, Wan-Sik; Chung, Ik-Joo; Kim, Kyung-Keun; Lee, Kyung-Hwa; Kweon, Sun-Seog; Joo, Young-Eun

2010-09-01

KAI1 COOH-terminal interacting tetraspanin (KITENIN) promotes tumor cell migration, invasion and metastasis in colon, bladder, head and neck cancer. The aims of current study were to evaluate whether KITENIN affects tumor cell behavior in human gastric cancer cell line and to document the expression of KITENIN in a well-defined series of gastric tumors, including complete long-term follow-up, with special reference to patient prognosis. To evaluate the impact of KITENIN knockdown on behavior of a human gastric cancer cell line, AGS, migration, invasion and proliferation assays using small-interfering RNA were performed. The expression of activator protein-1 (AP-1) target genes and AP-1 transcriptional activity were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and luciferase reporter assay. The expression of KITENIN and AP-1 target genes by RT-PCR and Western blotting or immunohistochemistry was also investigated in human gastric cancer tissues. The knockdown of KITENIN suppressed tumor cell migration, invasion and proliferation in AGS cells. The mRNA expression of matrix metalloproteinase-1 (MMP-1), MMP-3, cyclooxygenase-2 (COX-2), and CD44 was reduced by knockdown of KITENIN in AGS. AP-1 transcriptional activity was significantly decreased by knockdown of KITENIN in AGS cells. KITENIN expression was significantly increased in human cancer tissues at RNA and protein levels. Expression of MMP-1, MMP-3, COX-2 and CD44 were significantly increased in human gastric cancer tissues. Immunostaining of KITENIN was predominantly identified in the cytoplasm of cancer cells. Expression of KITENIN was significantly associated with tumor size, Lauren classification, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that KITENIN plays an important role in human gastric cancer progression by AP-1 activation.

Cardiotoxicity screening with simultaneous optogenetic pacing, voltage imaging and calcium imaging.

PubMed

Dempsey, Graham T; Chaudhary, Khuram W; Atwater, Nicholas; Nguyen, Cuong; Brown, Barry S; McNeish, John D; Cohen, Adam E; Kralj, Joel M

2016-01-01

The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative seeks an in vitro test to accurately predict clinical Torsades de Pointes (TdP). We developed a cardiotoxicity assay incorporating simultaneous measurement of the action potential (AP) waveform and Ca(2+) transient (CT) in human iPSC-derived cardiomyocytes (CMs). Concurrent optogenetic pacing provided a well-controlled electrophysiological background. We used the Optopatch platform for all-optical electrophysiology (Hochbaum et al., 2014). In a monolayer culture, a subset of cells expressed a genetically encoded, calcium and voltage reporter, CaViar (Hou, Kralj, Douglass, Engert, & Cohen, 2014), while others expressed a channelrhodopsin variant, CheRiff. Optical pacing of CheRiff-expressing cells synchronized the syncytium. We screened 12 compounds (11 acute, 1 chronic) to identify electrophysiological (AP rise time, AP50, AP90, beat rate) and CT effects in spontaneously beating and paced cultures (1Hz, 2Hz). CaViar reported spontaneous and paced APs and CTs with high signal-to-noise ratio and low phototoxicity. Quinidine, flecainide, E-4031, digoxin and cisapride prolonged APs, while verapamil and nifedipine shortened APs. Early after depolarizations (EADs) were elicited by quinidine, flecainide and cisapride. All but four compounds (amiodarone, chromanol, nifedipine, verapamil) prolonged AP rise time. Nifedipine and verapamil decreased CT amplitude, while digoxin increased CT amplitude. Pentamidine prolonged APs after chronic exposure. The Optopatch platform provides a robust assay to measure APs and CTs in hiPSC-CMs. This addresses the CiPA mandate and will facilitate comparisons of cell-based assays to human clinical data. Copyright © 2016 Elsevier Inc. All rights reserved.

Human Rights Education: A Framework for Social Study from the Interpersonal to the Global. Pull Out 1.

ERIC Educational Resources Information Center

Schmidt, Janet; Manson, Patrick

1999-01-01

Addresses human rights education (HRE) for young learners stressing the centrality of the Universal Declaration of Human Rights and the Convention on the Rights of the Child. Illustrates the use of HRE within history, geography, world cultures, and literature. Believes that HRE begins by creating a human rights community in the classroom. (CMK)

Cloning and Characterization of a Wheat Homologue of Apurinic/Apyrimidinic Endonuclease Ape1L

PubMed Central

Grin, Inga R.; Zharkov, Dmitry O.; Ishenko, Alexander A.; Tudek, Barbara; Bissenbaev, Amangeldy K.; Saparbaev, Murat

2014-01-01

Background Apurinic/apyrimidinic (AP) endonucleases are key DNA repair enzymes involved in the base excision repair (BER) pathway. In BER, an AP endonuclease cleaves DNA at AP sites and 3′-blocking moieties generated by DNA glycosylases and/or oxidative damage. A Triticum aestivum cDNA encoding for a putative homologue of ExoIII family AP endonucleases which includes E. coli Xth, human APE1 and Arabidopsis thaliana AtApe1L has been isolated and its protein product purified and characterized. Methodology/Principal Findings We report that the putative wheat AP endonuclease, referred here as TaApe1L, contains AP endonuclease, 3′-repair phosphodiesterase, 3′-phosphatase and 3′→5′ exonuclease activities. Surprisingly, in contrast to bacterial and human AP endonucleases, addition of Mg2+ and Ca2+ (5–10 mM) to the reaction mixture inhibited TaApe1L whereas the presence of Mn2+, Co2+ and Fe2+ cations (0.1–1.0 mM) strongly stimulated all its DNA repair activities. Optimization of the reaction conditions revealed that the wheat enzyme requires low divalent cation concentration (0.1 mM), mildly acidic pH (6–7), low ionic strength (20 mM KCl) and has a temperature optimum at around 20°C. The steady-state kinetic parameters of enzymatic reactions indicate that TaApe1L removes 3′-blocking sugar-phosphate and 3′-phosphate groups with good efficiency (k cat/K M = 630 and 485 μM−1·min−1, respectively) but possesses a very weak AP endonuclease activity as compared to the human homologue, APE1. Conclusions/Significance Taken together, these data establish the DNA substrate specificity of the wheat AP endonuclease and suggest its possible role in the repair of DNA damage generated by endogenous and environmental factors. PMID:24667595

Altered Impedance of Ear Acupuncture Point MT2 in Breast Cancer Patients: A Preliminary Observation

PubMed Central

Yang, Huayuan; Wang, Pin; Liu, Tangyi; Tang, Wenchao

2015-01-01

Skin impedance at acupuncture points (APs) has been used as a diagnostic aid for more than 50 years. In this study, we have a diagnostic tool (JXT-2008) to measure the skin impedance of ear APs of 30 breast cancer patients and the corresponding skin impedance of ear APs of 30 healthy humans, and then we compared these changes in ear AP impedance in breast cancer patients and healthy individuals. PMID:26504483

Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis.

PubMed

Skouras, Christos; Zheng, Xiaozhong; Binnie, Margaret; Homer, Natalie Z M; Murray, Toby B J; Robertson, Darren; Briody, Lesley; Paterson, Finny; Spence, Heather; Derr, Lisa; Hayes, Alastair J; Tsoumanis, Andreas; Lyster, Dawn; Parks, Rowan W; Garden, O James; Iredale, John P; Uings, Iain J; Liddle, John; Wright, Wayne L; Dukes, George; Webster, Scott P; Mole, Damian J

2016-09-27

Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R 2  = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R 2  = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction.

Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis

PubMed Central

Skouras, Christos; Zheng, Xiaozhong; Binnie, Margaret; Homer, Natalie Z. M.; Murray, Toby B. J.; Robertson, Darren; Briody, Lesley; Paterson, Finny; Spence, Heather; Derr, Lisa; Hayes, Alastair J.; Tsoumanis, Andreas; Lyster, Dawn; Parks, Rowan W.; Garden, O. James; Iredale, John P.; Uings, Iain J.; Liddle, John; Wright, Wayne L.; Dukes, George; Webster, Scott P.; Mole, Damian J.

2016-01-01

Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R2 = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R2 = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction. PMID:27669975

Exploitation of phosphorescent labelling reagent of fullerol-fluorescein isothiocyanate and new method for the determination of trace alkaline phosphatase as well as forecast of human diseases.

PubMed

Liu, Jia-Ming; Huang, Xiao-Mei; Liu, Zhen-Bo; Lin, Shao-Qin; Li, Fei-Ming; Gao, Fei; Li, Zhi-Ming; Zeng, Li-Qing; Li, Lian-Ying; Ouyang, Ying

2009-08-26

A new phosphorescent labelling reagent consisting of fullerol, fluorescein isothiocyanate and N,N-dimethylaniline (F-ol-(FITC)(n)-DMA) was developed. The mode of action is based on the reactivity of the active -OH group in F-ol with the -COOH group of FITC to form an F-ol-(FITC)(n)-DMA complex containing several FITC molecules. F-ol-(FITC)(n)-DMA increased the number of luminescent molecules in the biological target of WGA-AP-WGA-F-ol-(FITC)(n)-DMA (WGA and AP are wheat germ agglutinin and alkaline phosphatase, respectively) which improved the sensitivity using solid substrate room temperature phosphorimetry (SSRTP) detection. The proposed method provided high sensitivity and strong specificity for WGA-AP. The limit of detection (LD) was 0.15 ag AP spot(-1) for F-ol and 0.097 ag AP spot(-1) for FITC in F-ol-(FITC)(n)-DMA, which was lower than the method using single luminescent molecules of F-ol-DMA and FITC-DMA to label WGA (0.20 ag AP spot(-1) for F-ol-DMA and 0.22 ag AP spot(-1) for FITC-DMA). Results for the determination of AP in human serum were in good agreement with those obtained by enzyme-linked immunosorbent assay. The mechanism of F-ol-(FITC)(n)-DMA labelling of WGA was discussed.

Effects of a human recombinant alkaline phosphatase during impaired mitochondrial function in human renal proximal tubule epithelial cells.

PubMed

Peters, Esther; Schirris, Tom; van Asbeck, Alexander H; Gerretsen, Jelle; Eymael, Jennifer; Ashikov, Angel; Adjobo-Hermans, Merel J W; Russel, Frans; Pickkers, Peter; Masereeuw, Rosalinde

2017-02-05

Sepsis-associated acute kidney injury is a multifactorial syndrome in which inflammation and renal microcirculatory dysfunction play a profound role. Subsequently, renal tubule mitochondria reprioritize cellular functions to prevent further damage. Here, we investigated the putative protective effects of human recombinant alkaline phosphatase (recAP) during inhibition of mitochondrial respiration in conditionally immortalized human proximal tubule epithelial cells (ciPTEC). Full inhibition of mitochondrial oxygen consumption was obtained after 24h antimycin A treatment, which did not affect cell viability. While recAP did not affect the antimycin A-induced decreased oxygen consumption and increased hypoxia-inducible factor-1α or adrenomedullin gene expression levels, the antimycin A-induced increase of pro-inflammatory cytokines IL-6 and IL-8 was attenuated. Antimycin A tended to induce the release of detrimental purines ATP and ADP, which reached statistical significance when antimycin A was co-incubated with lipopolysaccharide, and were completely converted into cytoprotective adenosine by recAP. As the adenosine A 2A receptor was up-regulated after antimycin A exposure, an adenosine A 2A receptor knockout ciPTEC cell line was generated in which recAP still provided protection. Together, recAP did not affect oxygen consumption but attenuated the inflammatory response during impaired mitochondrial function, an effect suggested to be mediated by dephosphorylating ATP and ADP into adenosine. Copyright © 2016 Elsevier B.V. All rights reserved.

The thing that should not be: predictive coding and the uncanny valley in perceiving human and humanoid robot actions

PubMed Central

Chaminade, Thierry; Ishiguro, Hiroshi; Driver, Jon; Frith, Chris

2012-01-01

Using functional magnetic resonance imaging (fMRI) repetition suppression, we explored the selectivity of the human action perception system (APS), which consists of temporal, parietal and frontal areas, for the appearance and/or motion of the perceived agent. Participants watched body movements of a human (biological appearance and movement), a robot (mechanical appearance and movement) or an android (biological appearance, mechanical movement). With the exception of extrastriate body area, which showed more suppression for human like appearance, the APS was not selective for appearance or motion per se. Instead, distinctive responses were found to the mismatch between appearance and motion: whereas suppression effects for the human and robot were similar to each other, they were stronger for the android, notably in bilateral anterior intraparietal sulcus, a key node in the APS. These results could reflect increased prediction error as the brain negotiates an agent that appears human, but does not move biologically, and help explain the ‘uncanny valley’ phenomenon. PMID:21515639

The Wheel Model of STEAM Education Based on Traditional Korean Scientific Contents

ERIC Educational Resources Information Center

Kim, Pyoung Won

2016-01-01

The Korean STEAM education pursues a convergent human resources education, but there are shortcomings associated with it due to the fact that it excludes the Humanities in its curriculum. This study embodies the accomplishments from the design and field application of the STEAM education model that has added Humanities fields (history, geography,…

Geography as destiny? Social and ecological resilience in rangelands of the American southwest

USDA-ARS?s Scientific Manuscript database

Background/Question/Methods: Social-ecological systems perspectives focus on the reciprocal relationships between human and natural ecosystem elements and how these interactions determine human well-being, ecological state change, and land use change. In the arid southwestern US, which is dominated...

HOW HUMAN HISTORY HAS INFLUENCED GEOGRAPHY AND GENETICS OF PARASITE POPULATIONS

USDA-ARS?s Scientific Manuscript database

Human beings have radically altered agricultural landscapes, establishing a limited repertoire of plants and animals over vast expanses. Here, I consider what impact such a history may have had on the distribution and diversity of animal parasite, hypothesizing that certain parasites may have been '...

Determination of L-AP4-bound human mGlu8 receptor amino terminal domain structure and the molecular basis for L-AP4’s group III mGlu receptor functional potency and selectivity

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

Schkeryantz, Jeffery M.; Chen, Qi; Ho, Joseph D.

Here, L-2-Amino-4-phosphonobutyric acid (L-AP4) is a known potent and selective agonist for the Group III mGlu receptors. However, it does not show any selectivity among the individual group III mGlu subtypes. In order to understand the molecular basis for this group selectivity, we solved the first human mGlu8 amino terminal domain (ATD) crystal structures in complex with L-glu and L-AP4. In comparison with other published L-glu-bound mGlu ATD structures, we have observed L-glu binds in a significantly different manner in mGlu1. Furthermore, these new structures provided evidence that both the electronic and steric nature of the distal phosphate of L-AP4more » contribute to its exquisite Group III functional agonist potency and selectivity.« less

Human Pathogen Shown to Cause Disease in the Threatened Eklhorn Coral Acropora palmata

PubMed Central

Sutherland, Kathryn Patterson; Shaban, Sameera; Joyner, Jessica L.; Porter, James W.; Lipp, Erin K.

2011-01-01

Coral reefs are in severe decline. Infections by the human pathogen Serratia marcescens have contributed to precipitous losses in the common Caribbean elkhorn coral, Acropora palmata, culminating in its listing under the United States Endangered Species Act. During a 2003 outbreak of this coral disease, called acroporid serratiosis (APS), a unique strain of the pathogen, Serratia marcescens strain PDR60, was identified from diseased A. palmata, human wastewater, the non-host coral Siderastrea siderea and the corallivorous snail Coralliophila abbreviata. In order to examine humans as a source and other marine invertebrates as vectors and/or reservoirs of the APS pathogen, challenge experiments were conducted with A. palmata maintained in closed aquaria to determine infectivity of strain PDR60 from reef and wastewater sources. Strain PDR60 from wastewater and diseased A. palmata caused disease signs in elkhorn coral in as little as four and five days, respectively, demonstrating that wastewater is a definitive source of APS and identifying human strain PDR60 as a coral pathogen through fulfillment of Koch's postulates. A. palmata inoculated with strain PDR60 from C. abbreviata showed limited virulence, with one of three inoculated fragments developing APS signs within 13 days. Strain PDR60 from non-host coral S. siderea showed a delayed pathogenic effect, with disease signs developing within an average of 20 days. These results suggest that C. abbreviata and non-host corals may function as reservoirs or vectors of the APS pathogen. Our results provide the first example of a marine “reverse zoonosis” involving the transmission of a human pathogen (S. marcescens) to a marine invertebrate (A. palmata). These findings underscore the interaction between public health practices and environmental health indices such as coral reef survival. PMID:21858132

Intrinsic neurophysiological properties of hilar ectopic and normotopic dentate granule cells in human temporal lobe epilepsy and a rat model.

PubMed

Althaus, A L; Sagher, O; Parent, J M; Murphy, G G

2015-02-15

Hilar ectopic dentate granule cells (DGCs) are a salient feature of aberrant plasticity in human temporal lobe epilepsy (TLE) and most rodent models of the disease. Recent evidence from rodent TLE models suggests that hilar ectopic DGCs contribute to hyperexcitability within the epileptic hippocampal network. Here we investigate the intrinsic excitability of DGCs from humans with TLE and the rat pilocarpine TLE model with the objective of comparing the neurophysiology of hilar ectopic DGCs to their normotopic counterparts in the granule cell layer (GCL). We recorded from 36 GCL and 7 hilar DGCs from human TLE tissue. Compared with GCL DGCs, hilar DGCs in patient tissue exhibited lower action potential (AP) firing rates, more depolarized AP threshold, and differed in single AP waveform, consistent with an overall decrease in excitability. To evaluate the intrinsic neurophysiology of hilar ectopic DGCs, we made recordings from retrovirus-birthdated, adult-born DGCs 2-4 mo after pilocarpine-induced status epilepticus or sham treatment in rats. Hilar DGCs from epileptic rats exhibited higher AP firing rates than normotopic DGCs from epileptic or control animals. They also displayed more depolarized resting membrane potential and wider AP waveforms, indicating an overall increase in excitability. The contrasting findings between disease and disease model may reflect differences between the late-stage disease tissue available from human surgical specimens and the earlier disease stage examined in the rat TLE model. These data represent the first neurophysiological characterization of ectopic DGCs from human hippocampus and prospectively birthdated ectopic DGCs in a rodent TLE model. Copyright © 2015 the American Physiological Society.

Regulation of rat mesangial cell growth by diadenosine phosphates.

PubMed Central

Heidenreich, S; Tepel, M; Schlüter, H; Harrach, B; Zidek, W

1995-01-01

The newly recognized human endogenous vasoconstrictive dinucleotides, diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A), were tested for growth stimulatory effects in rat mesangial cells (MC). Both AP5A and AP6A stimulated growth in micromolar concentrations. The growth stimulatory effect exceeded that of ATP, alpha,beta-methylene ATP, adenosine 5'-O-(3-thio)triphosphate and UTP. Both diadenosine phosphates potentiated the growth response to platelet-derived growth factor, but not to insulin-like growth factor-1. To further elucidate the site of action in the cell cycle, RNA and protein synthesis were assessed. AP5 and AP6A stimulated protein synthesis, but not RNA formation. Furthermore, both agents increased cytosolic free Ca2+ concentration. It is concluded that AP5A and AP6A may play a regulatory role in MC growth as progression factors and possibly modify MC proliferation in glomerular disease. PMID:7769127

Alkaline phosphatase protects against renal inflammation through dephosphorylation of lipopolysaccharide and adenosine triphosphate.

PubMed

Peters, E; Geraci, S; Heemskerk, S; Wilmer, M J; Bilos, A; Kraenzlin, B; Gretz, N; Pickkers, P; Masereeuw, R

2015-10-01

Recently, two phase-II trials demonstrated improved renal function in critically ill patients with sepsis-associated acute kidney injury treated with the enzyme alkaline phosphatase. Here, we elucidated the dual active effect on renal protection of alkaline phosphatase. The effect of human recombinant alkaline phosphatase (recAP) on LPS-induced renal injury was studied in Sprague-Dawley rats. Renal function was assessed by transcutaneous measurement of FITC-sinistrin elimination in freely moving, awake rats. The mechanism of action of recAP was further investigated in vitro using conditionally immortalized human proximal tubular epithelial cells (ciPTEC). In vivo, LPS administration significantly prolonged FITC-sinistrin half-life and increased fractional urea excretion, which was prevented by recAP co-administration. Moreover, recAP prevented LPS-induced increase in proximal tubule injury marker, kidney injury molecule-1 expression and excretion. In vitro, LPS-induced production of TNF-α, IL-6 and IL-8 was significantly attenuated by recAP. This effect was linked to dephosphorylation, as enzymatically inactive recAP had no effect on LPS-induced cytokine production. RecAP-mediated protection resulted in increased adenosine levels through dephosphorylation of LPS-induced extracellular ADP and ATP. Also, recAP attenuated LPS-induced increased expression of adenosine A2A receptor. However, the A2A receptor antagonist ZM-241385 did not diminish the effects of recAP. These results indicate that the ability of recAP to reduce renal inflammation may account for the beneficial effect observed in septic acute kidney injury patients, and that dephosphorylation of ATP and LPS are responsible for this protective effect. © 2015 The British Pharmacological Society.

Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats.

PubMed

Jung, Kyung Hee; Song, Sun U; Yi, Tacghee; Jeon, Myung-Shin; Hong, Sang-Won; Zheng, Hong-Mei; Lee, Hee-Seung; Choi, Myung-Joo; Lee, Don-Haeng; Hong, Soon-Sun

2011-03-01

Acute pancreatitis (AP) has a high mortality rate; repetitive AP induces chronic AP and pancreatic adenocarcinoma. Mesenchymal stem cells (MSCs) have immunoregulatory effects and reduce inflammation. We developed a protocol to isolate human bone marrow-derived clonal MSCs (hcMSCs) from bone marrow aspirate and investigated the effects of these cells in rat models of mild and severe AP. Mild AP was induced in Sprague-Dawley rats by 3 intraperitoneal injections of cerulein (100 μg/kg), given at 2-hour intervals; severe AP was induced by intraparenchymal injection of 3% sodium taurocholate solution. hcMSCs were labeled with CM-1,1'-dioctadecyl-3,3,3'-tetramethylindo-carbocyanine perchloride and administered to rats through the tail vein. hcMSCs underwent self-renewal and had multipotent differentiation capacities and immunoregulatory functions. Greater numbers of infused hcMSCs were detected in pancreas of rats with mild and severe AP than of control rats. Infused hcMSCs reduced acinar-cell degeneration, pancreatic edema, and inflammatory cell infiltration in each model of pancreatitis. The hcMSCs reduced expression of inflammation mediators and cytokines in rats with mild and severe AP. hcMSCs suppressed the mixed lymphocyte reaction and increased expression of Foxp3(+) (a marker of regulatory T cells) in cultured rat lymph node cells. Rats with mild or severe AP that were given infusions of hcMSCs had reduced numbers of CD3(+) T cells and increased expression of Foxp3(+) in pancreas tissues. hcMSCs reduced inflammation and damage to pancreatic tissue in a rat model of AP; they reduced levels of cytokines and induced numbers of Foxp3(+) regulatory T cells. hcMSCs might be developed as a cell therapy for pancreatitis. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Two Anaplasma phagocytophilum Strains in Ixodes scapularis Ticks, Canada

PubMed Central

Krakowetz, Chantel N.; Dibernardo, Antonia; Lindsay, L. Robbin

2014-01-01

We developed PCR-based assays to distinguish a human pathogenic strain of Anaplasma phagocytophilum, Ap-ha, from Ap-variant 1, a strain not associated with human infection. The assays were validated on A. phagocytophilum-infected blacklegged ticks (Ixodes scapularis) collected in Canada. The relative prevalence of these 2 strains in I. scapularis ticks differed among geographic regions. PMID:25417645

Tiron Inhibits UVB-Induced AP-1 Binding Sites Transcriptional Activation on MMP-1 and MMP-3 Promoters by MAPK Signaling Pathway in Human Dermal Fibroblasts

PubMed Central

Zhang, Chao; Zhao, Mei; Zhang, Quan-Wu; Gao, Feng-Hou

2016-01-01

Recent research found that Tiron was an effective antioxidant that could act as the intracellular reactive oxygen species (ROS) scavenger or alleviate the acute toxic metal overload in vivo. In this study, we investigated the inhibitory effect of Tiron on matrix metalloproteinase (MMP)-1 and MMP-3 expression in human dermal fibroblast cells. Western blot and ELISA analysis revealed that Tiron inhibited ultraviolet B (UVB)-induced protein expression of MMP-1 and MMP-3. Real-time quantitative PCR confirmed that Tiron could inhibit UVB-induced mRNA expression of MMP-1 and MMP-3. Furthermore, Tiron significantly blocked UVB-induced activation of the MAPK signaling pathway and activator protein (AP)-1 in the downstream of this transduction pathway in fibroblasts. Through the AP-1 binding site mutation, it was found that Tiron could inhibit AP-1-induced upregulation of MMP-1 and MMP-3 expression through blocking AP-1 binding to the AP-1 binding sites in the MMP-1 and MMP-3 promoter region. In conclusion, Tiron may be a novel antioxidant for preventing and treating skin photoaging UV-induced. PMID:27486852

Isolation of a small molecule inhibitor of DNA base excision repair

PubMed Central

Madhusudan, Srinivasan; Smart, Fiona; Shrimpton, Paul; Parsons, Jason L.; Gardiner, Laurence; Houlbrook, Sue; Talbot, Denis C.; Hammonds, Timothy; Freemont, Paul A.; Sternberg, Michael J. E.; Dianov, Grigory L.; Hickson, Ian D.

2005-01-01

The base excision repair (BER) pathway is essential for the removal of DNA bases damaged by alkylation or oxidation. A key step in BER is the processing of an apurinic/apyrimidinic (AP) site intermediate by an AP endonuclease. The major AP endonuclease in human cells (APE1, also termed HAP1 and Ref-1) accounts for >95% of the total AP endonuclease activity, and is essential for the protection of cells against the toxic effects of several classes of DNA damaging agents. Moreover, APE1 overexpression has been linked to radio- and chemo-resistance in human tumors. Using a newly developed high-throughput screen, several chemical inhibitors of APE1 have been isolated. Amongst these, CRT0044876 was identified as a potent and selective APE1 inhibitor. CRT0044876 inhibits the AP endonuclease, 3′-phosphodiesterase and 3′-phosphatase activities of APE1 at low micromolar concentrations, and is a specific inhibitor of the exonuclease III family of enzymes to which APE1 belongs. At non-cytotoxic concentrations, CRT0044876 potentiates the cytotoxicity of several DNA base-targeting compounds. This enhancement of cytotoxicity is associated with an accumulation of unrepaired AP sites. In silico modeling studies suggest that CRT0044876 binds to the active site of APE1. These studies provide both a novel reagent for probing APE1 function in human cells, and a rational basis for the development of APE1-targeting drugs for antitumor therapy. PMID:16113242

Sources of Information on Medical Geography

PubMed Central

Mullins, Lynn S.

1966-01-01

Adequate research in the peripheral field of medical geography requires familiarity with the literature of medicine, geography, and other environmentally oriented fields. The pertinent literature of the two primary disciplines, as well as that of anthropology, nutrition, and human bioclimatology, is surveyed from a bibliographical point of view. A brief review of historical sources is presented, followed by a discussion of the contemporary organizations, both international and national, active in the field. Emphasis is placed on the publishing programs and projects, maps, atlases, symposia, reports, and other literature sponsored or stimulated by these organizations. Regional bibliographical surveys for East Africa, India, and the Soviet Union are also noted. Pertinent aspects of bibliographies, indexes, abstracts, library card catalogs and accession lists, and other resources are listed, with emphasis on the various subject headings and other approaches to them. Throughout, the sources of information are approached from a multidisciplinary and interdisciplinary viewpoint. PMID:5329543

Sources of information on medical geography.

PubMed

Mullins, L S

1966-07-01

Adequate research in the peripheral field of medical geography requires familiarity with the literature of medicine, geography, and other environmentally oriented fields. The pertinent literature of the two primary disciplines, as well as that of anthropology, nutrition, and human bioclimatology, is surveyed from a bibliographical point of view. A brief review of historical sources is presented, followed by a discussion of the contemporary organizations, both international and national, active in the field. Emphasis is placed on the publishing programs and projects, maps, atlases, symposia, reports, and other literature sponsored or stimulated by these organizations. Regional bibliographical surveys for East Africa, India, and the Soviet Union are also noted. Pertinent aspects of bibliographies, indexes, abstracts, library card catalogs and accession lists, and other resources are listed, with emphasis on the various subject headings and other approaches to them. Throughout, the sources of information are approached from a multidisciplinary and interdisciplinary viewpoint.

A polymorphic region in the human transcription factor AP-2beta gene is associated with specific personality traits.

PubMed

Damberg, M; Garpenstrand, H; Alfredsson, J; Ekblom, J; Forslund, K; Rylander, G; Oreland, L

2000-03-01

Transcription factor AP-2beta is implicated in playing an important role during embryonic development of different parts of the brain, eg, midbrain, hindbrain, spinal cord, dorsal and cranial root ganglia.1,2 The gene encoding AP-2beta contains a polymorphic region which includes a tetranucleotide repeat of [CAAA] four or five times, located in intron 2 between nucleotides 12593 and 12612.3 Since the midbrain contains structures important for variables such as mood and personality, we have investigated if the AP-2beta genotype is associated with personality traits estimated by the Karolinska Scales of Personality (KSP). Identification of transcription factor genes as candidate genes in psychiatric disorders is a novel approach to further elucidate the genetic factors that, together with environmental factors, are involved in the expression of specific psychiatric phenotypes. The AP-2beta genotype and KSP scores were determined for 137 Caucasian volunteers (73 females and 64 males). The personality traits muscular tension, guilt, somatic anxiety, psychastenia and indirect aggression were significantly associated with the specific AP-2beta genotype, albeit with significant difference between genders. Based on this result the human AP-2beta gene seems to be an important candidate gene for personality disorders. Moreover, the present results suggest that the structure of the intron 2 region of the AP-2beta gene is one factor that contributes to development of the constitutional component of specific personality traits.

Elevated increases in human-perceived temperature under climate warming

NASA Astrophysics Data System (ADS)

Li, Jianfeng; Chen, Yongqin David; Gan, Thian Yew; Lau, Ngar-Cheung

2018-01-01

Changes in air temperature (AT), humidity and wind speed (Wind) affect apparent temperature (AP), the human-perceived equivalent temperature1-3. Here we show that under climate warming, both reanalysis data sets and Global Climate Model simulations indicate that AP has increased faster than AT over land. The faster increase in AP has been especially significant over low latitudes and is expected to continue in the future. The global land average AP increased at 0.04 °C per decade faster than AT before 2005. This trend is projected to increase to 0.06 °C (0.03-0.09 °C; minimum and maximum of the ensemble members) per decade and 0.17 °C (0.12-0.25 °C) per decade under the Representative Concentration Pathway 4.5 scenario (RCP4.5) and RCP8.5, respectively, and reduce to 0.02 °C (0-0.03 °C) per decade under RCP2.6 over 2006-2100. The higher increment in AP in summer daytime is more remarkable than in winter night-time and is most prominent over low latitudes. The summertime increases in AT-based thermal discomfort are projected to balance the wintertime decreases in AT-based discomfort over low and middle latitudes, while the summertime increases in AP-based thermal discomfort are expected to outpace the wintertime decreases in AP-based thermal discomfort. Effective climate change mitigation efforts to achieve RCP2.6 can considerably alleviate the faster increase in AP.

A beta-N-acetylglucosaminyl phosphate diester residue is attached to the glycosylphosphatidylinositol anchor of human placental alkaline phosphatase: a target of the channel-forming toxin aerolysin.

PubMed

Fukushima, Keiko; Ikehara, Yukio; Kanai, Michiko; Kochibe, Naohisa; Kuroki, Masahide; Yamashita, Katsuko

2003-09-19

Glycosylphosphatidylinositol (GPI)-anchored proteins are ubiquitous in eukaryotes. The minimum conserved GPI core structure of all GPI-anchored glycans has been determined as EtN-PO4-6Manalpha1-2Manalpha1-6Manalpha1-4GlcN-myo-inositol-PO3H. Human placental alkaline phosphatase (AP) has been reported to be a GPI-anchored membrane protein. AP carries one N-glycan, (NeuAcalpha2-->3)2Gal2GlcNAc2Man3GlcNAc(+/-Fuc)GlcNAc, and a GPI anchor, which contains an ethanolamine phosphate diester group, as a side chain. However, we found that both sialidase-treated soluble AP (sAP) and its GPI-anchored glycan bound to a Psathyrella velutina lectin (PVL)-Sepharose column, which binds beta-GlcNAc residues. PVL binding of asialo-sAP and its GPI-anchored glycan was diminished by digestion with diplococcal beta-N-acetylhexosaminidase or by mild acid treatment. After sequential digestion of asialo-sAP with beta-N-acetylhexosaminidase and acid phosphatase, the elution patterns on chromatofocusing gels were changed in accordance with the negative charges of phosphate residues. Trypsin-digested sAP was analyzed by liquid chromatography/electrospray ionization mass spectrometry, and the structures of two glycopeptides with GPI-anchored glycans were confirmed as peptide-EtN-PO4-6Manalpha1-->2(GlcNAcbeta1-PO4-->6)Manalpha1-6(+/-EtN-PO4-->)Manalpha1-->4GlcN, which may be produced by endo-alpha-glucosaminidase. In addition to AP, GPI-anchored carcinoembryonic antigen, cholinesterase, and Tamm-Horsfall glycoprotein also bound to a PVL-Sepharose column, suggesting that the beta-N-acetylglucosaminyl phosphate diester residue is widely distributed in human GPI-anchored glycans. Furthermore, we found that the beta-N-acetylglucosaminyl phosphate diester residue is important for GPI anchor recognition of aerolysin, a channel-forming toxin derived from Aeromonas hydrophila.

Mechanism of action of novel lung edema therapeutic AP301 by activation of the epithelial sodium channel.

PubMed

Shabbir, Waheed; Scherbaum-Hazemi, Parastoo; Tzotzos, Susan; Fischer, Bernhard; Fischer, Hendrik; Pietschmann, Helmut; Lucas, Rudolf; Lemmens-Gruber, Rosa

2013-12-01

AP301 [Cyclo(CGQRETPEGAEAKPWYC)], a cyclic peptide comprising the human tumor necrosis factor lectin-like domain (TIP domain) sequence, is currently being developed as a treatment for lung edema and has been shown to reduce extravascular lung water and improve lung function in mouse, rat, and pig models. The current paradigm for liquid homeostasis in the adult mammalian lung is that passive apical uptake of sodium via the amiloride-sensitive epithelial Na⁺ channel (ENaC) and nonselective cyclic-nucleotide-gated cation channels creates the major driving force for reabsorption of water through the alveolar epithelium in addition to other ion channels such as potassium and chloride channels. AP301 can increase amiloride-sensitive current in A549 cells as well as in freshly isolated type II alveolar epithelial cells from different species. ENaC is expressed endogenously in all of these cell types. Consequently, this study was undertaken to determine whether ENaC is the specific target of AP301. The effect of AP301 in A549 cells as well as in human embryonic kidney cells and Chinese hamster ovary cells heterologously expressing human ENaC subunits (α, β, γ, and δ) was measured in patch clamp experiments. The congener TIP peptide AP318 [Cyclo(4-aminobutanoic acid-GQRETPEGAEAKPWYD)] activated ENaC by increasing single-channel open probability. AP301 increased current in proteolytically activated (cleaved) but not near-silent (uncleaved) ENaC in a reversible manner. αβγ- or δβγ-ENaC coexpression was required for maximal activity. No increase in current was observed after deglycosylation of extracellular domains of ENaC. Thus, our data suggest that the specific interaction of AP301 with both endogenously and heterologously expressed ENaC requires precedent binding to glycosylated extracellular loop(s).

Assessing Tsunami Vulnerabilities of Geographies with Shallow Water Equations

NASA Technical Reports Server (NTRS)

Aras, Rifat; Shen, Yuzhong

2012-01-01

Tsunami preparedness is crucial for saving human lives in case of disasters that involve massive water movement. In this work, we develop a framework for visual assessment of tsunami preparedness of geographies. Shallow water equations (also called Saint Venant equations) are a set of hyperbolic partial differential equations that are derived by depth-integrating the Navier-Stokes equations and provide a great abstraction of water masses that have lower depths compared to their free surface area. Our specific contribution in this study is to use Microsoft's XNA Game Studio to import underwater and shore line geographies, create different tsunami scenarios, and visualize the propagation of the waves and their impact on the shore line geography. Most importantly, we utilized the computational power of graphical processing units (GPUs) as HLSL based shader files and delegated all of the heavy computations to the GPU. Finally, we also conducted a validation study, in which we have tested our model against a controlled shallow water experiment. We believe that such a framework with an easy to use interface that is based on readily available software libraries, which are widely available and easily distributable, would encourage not only researchers, but also educators to showcase ideas.

A Novel GLP1 Receptor Interacting Protein ATP6ap2 Regulates Insulin Secretion in Pancreatic Beta Cells*

PubMed Central

Dai, Feihan F.; Bhattacharjee, Alpana; Liu, Ying; Batchuluun, Battsetseg; Zhang, Ming; Wang, Xinye Serena; Huang, Xinyi; Luu, Lemieux; Zhu, Dan; Gaisano, Herbert; Wheeler, Michael B.

2015-01-01

GLP1 activates its receptor, GLP1R, to enhance insulin secretion. The activation and transduction of GLP1R requires complex interactions with a host of accessory proteins, most of which remain largely unknown. In this study, we used membrane-based split ubiquitin yeast two-hybrid assays to identify novel GLP1R interactors in both mouse and human islets. Among these, ATP6ap2 (ATPase H+-transporting lysosomal accessory protein 2) was identified in both mouse and human islet screens. ATP6ap2 was shown to be abundant in islets including both alpha and beta cells. When GLP1R and ATP6ap2 were co-expressed in beta cells, GLP1R was shown to directly interact with ATP6ap2, as assessed by co-immunoprecipitation. In INS-1 cells, overexpression of ATP6ap2 did not affect insulin secretion; however, siRNA knockdown decreased both glucose-stimulated and GLP1-induced insulin secretion. Decreases in GLP1-induced insulin secretion were accompanied by attenuated GLP1 stimulated cAMP accumulation. Because ATP6ap2 is a subunit required for V-ATPase assembly of insulin granules, it has been reported to be involved in granule acidification. In accordance with this, we observed impaired insulin granule acidification upon ATP6ap2 knockdown but paradoxically increased proinsulin secretion. Importantly, as a GLP1R interactor, ATP6ap2 was required for GLP1-induced Ca2+ influx, in part explaining decreased insulin secretion in ATP6ap2 knockdown cells. Taken together, our findings identify a group of proteins that interact with the GLP1R. We further show that one interactor, ATP6ap2, plays a novel dual role in beta cells, modulating both GLP1R signaling and insulin processing to affect insulin secretion. PMID:26272612

Enhanced cortical connectivity in absolute pitch musicians: a model for local hyperconnectivity.

PubMed

Loui, Psyche; Li, H Charles; Hohmann, Anja; Schlaug, Gottfried

2011-04-01

Connectivity in the human brain has received increased scientific interest in recent years. Although connection disorders can affect perception, production, learning, and memory, few studies have associated brain connectivity with graded variations in human behavior, especially among normal individuals. One group of normal individuals who possess unique characteristics in both behavior and brain structure is absolute pitch (AP) musicians, who can name the appropriate pitch class of any given tone without a reference. Using diffusion tensor imaging and tractography, we observed hyperconnectivity in bilateral superior temporal lobe structures linked to AP possession. Furthermore, volume of tracts connecting left superior temporal gyrus to left middle temporal gyrus predicted AP performance. These findings extend previous reports of exaggerated temporal lobe asymmetry, may explain the higher incidence of AP in special populations, and may provide a model for understanding the heightened connectivity that is thought to underlie savant skills and cases of exceptional creativity.

Enhanced Cortical Connectivity in Absolute Pitch Musicians: A Model for Local Hyperconnectivity

PubMed Central

Loui, Psyche; Charles Li, Hui C.; Hohmann, Anja; Schlaug, Gottfried

2010-01-01

Connectivity in the human brain has received increased scientific interest in recent years. Although connection disorders can affect perception, production, learning, and memory, few studies have associated brain connectivity with graded variations in human behavior, especially among normal individuals. One group of normal individuals who possess unique characteristics in both behavior and brain structure is absolute pitch (AP) musicians, who can name the appropriate pitch class of any given tone without a reference. Using diffusion tensor imaging and tractography, we observed hyperconnectivity in bilateral superior temporal lobe structures linked to AP possession. Furthermore, volume of tracts connecting left superior temporal gyrus to left middle temporal gyrus predicted AP performance. These findings extend previous reports of exaggerated temporal lobe asymmetry, may explain the higher incidence of AP in developmental disorders, and may provide a model for understanding the heightened connectivity that is thought to underlie savant skills and cases of exceptional creativity. PMID:20515408

Impact of ionic current variability on human ventricular cellular electrophysiology.

PubMed

Romero, Lucía; Pueyo, Esther; Fink, Martin; Rodríguez, Blanca

2009-10-01

Abnormalities in repolarization and its rate dependence are known to be related to increased proarrhythmic risk. A number of repolarization-related electrophysiological properties are commonly used as preclinical biomarkers of arrhythmic risk. However, the variability and complexity of repolarization mechanisms make the use of cellular biomarkers to predict arrhythmic risk preclinically challenging. Our goal is to investigate the role of ionic current properties and their variability in modulating cellular biomarkers of arrhythmic risk to improve risk stratification and identification in humans. A systematic investigation into the sensitivity of the main preclinical biomarkers of arrhythmic risk to changes in ionic current conductances and kinetics was performed using computer simulations. Four stimulation protocols were applied to the ten Tusscher and Panfilov human ventricular model to quantify the impact of +/-15 and +/-30% variations in key model parameters on action potential (AP) properties, Ca(2+) and Na(+) dynamics, and their rate dependence. Simulations show that, in humans, AP duration is moderately sensitive to changes in all repolarization current conductances and in L-type Ca(2+) current (I(CaL)) and slow component of the delayed rectifier current (I(Ks)) inactivation kinetics. AP triangulation, however, is strongly dependent only on inward rectifier K(+) current (I(K1)) and delayed rectifier current (I(Kr)) conductances. Furthermore, AP rate dependence (i.e., AP duration rate adaptation and restitution properties) and intracellular Ca(2+) and Na(+) levels are highly sensitive to both I(CaL) and Na(+)/K(+) pump current (I(NaK)) properties. This study provides quantitative insights into the sensitivity of preclinical biomarkers of arrhythmic risk to variations in ionic current properties in humans. The results show the importance of sensitivity analysis as a powerful method for the in-depth validation of mathematical models in cardiac electrophysiology.

Perfect pitch reconsidered.

PubMed

Moulton, Calum

2014-10-01

Perfect pitch, or absolute pitch (AP), is defined as the ability to identify or produce the pitch of a sound without need for a reference pitch, and is generally regarded as a valuable asset to the musician. However, there has been no recent review of the literature examining its aetiology and its utility taking into account emerging scientific advances in AP research, notably in functional imaging. This review analyses the key empirical research on AP, focusing on genetic and neuroimaging studies. The review concludes that: AP probably has a genetic predisposition, although this is based on limited evidence; early musical training is almost certainly essential for AP acquisition; and, although there is evidence that it may be relevant to speech processing, AP can interfere with relative pitch, an ability on which humans rely to communicate effectively. The review calls into question the value of AP to musicians and non-musicians alike. © 2014 Royal College of Physicians.

Selective inhibition by harmane of the apurinic apyrimidinic endonuclease activity of phage T4-induced UV endonuclease.

PubMed

Warner, H R; Persson, M L; Bensen, R J; Mosbaugh, D W; Linn, S

1981-11-25

1-Methyl-9H-pyrido-[3,4-b]indole (harmane) inhibits the apurinic/apyrimidinic (AP) endonuclease activity of the UV endonuclease induced by phage T4, whereas it stimulates the pyrimidine dimer-DNA glycosylase activity of that enzyme. E. coli endonuclease IV, E. coli endonuclease VI (the AP endonuclease activity associated with E. coli exonuclease III), and E. coli uracil-DNA glycosylase were not inhibited by harmane. Human fibroblast AP endonucleases I and II also were only slightly inhibited. Therefore, harmane is neither a general inhibitor of AP endonucleases, nor a general inhibitor of Class I AP endonucleases which incise DNA on the 3'-side of AP sites. However, E. coli endonuclease III and its associated dihydroxythymine-DNA glycosylase activity were both inhibited by harmane. This observation suggests that harmane may inhibit only AP endonucleases which have associated glycosylase activities.

Selective inhibition by harmane of the apurinic apyrimidinic endonuclease activity of phage T4-induced UV endonuclease.

PubMed Central

Warner, H R; Persson, M L; Bensen, R J; Mosbaugh, D W; Linn, S

1981-01-01

1-Methyl-9H-pyrido-[3,4-b]indole (harmane) inhibits the apurinic/apyrimidinic (AP) endonuclease activity of the UV endonuclease induced by phage T4, whereas it stimulates the pyrimidine dimer-DNA glycosylase activity of that enzyme. E. coli endonuclease IV, E. coli endonuclease VI (the AP endonuclease activity associated with E. coli exonuclease III), and E. coli uracil-DNA glycosylase were not inhibited by harmane. Human fibroblast AP endonucleases I and II also were only slightly inhibited. Therefore, harmane is neither a general inhibitor of AP endonucleases, nor a general inhibitor of Class I AP endonucleases which incise DNA on the 3'-side of AP sites. However, E. coli endonuclease III and its associated dihydroxythymine-DNA glycosylase activity were both inhibited by harmane. This observation suggests that harmane may inhibit only AP endonucleases which have associated glycosylase activities. PMID:6273822

Stunted by climate

NASA Astrophysics Data System (ADS)

2011-11-01

With expertise in geography and human health, Marta Jankowska and David López-Carr worked with a team of specialists in climate science, statistics, demography and policy to study climate change impacts on child malnutrition in Mali.

Anti-Inflammatory Effect of Apigenin on LPS-Induced Pro-Inflammatory Mediators and AP-1 Factors in Human Lung Epithelial Cells.

PubMed

Patil, Rajeshwari H; Babu, R L; Naveen Kumar, M; Kiran Kumar, K M; Hegde, Shubha M; Nagesh, Rashmi; Ramesh, Govindarajan T; Sharma, S Chidananda

2016-02-01

Apigenin is one of the plant flavonoids present in fruits and vegetables, acting as an important nutraceutical component. It is recognized as a potential antioxidant, antimicrobial, and anti-inflammatory molecule. In the present study, the mechanism of anti-inflammatory action of apigenin on lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and activator protein-1 (AP-1) factors in human lung A549 cells was investigated. The anti-inflammatory activity of apigenin on LPS-induced inflammation was determined by analyzing the expression of pro-inflammatory cytokines, nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and different AP-1 factors. Apigenin significantly inhibited the LPS-induced expression of iNOS, COX-2, expression of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, and TNF-α), and AP-1 proteins (c-Jun, c-Fos, and JunB) including nitric oxide production. Study confirms the anti-inflammatory effect of apigenin by inhibiting the expression of inflammatory mediators and AP-1 factors involved in the inflammation and its importance in the treatment of lung inflammatory diseases.

Pedagogy of Refuge: Education in a Time of Dispossession

ERIC Educational Resources Information Center

Perumal, Juliet Christine

2013-01-01

Despite its chequered history in relation to human rights issues, South Africa has been playing host to peoples displaced and dispossessed by geographies of anger and war, poverty, economic meltdown and other human rights atrocities. Perceiving South Africa as a sanctuary, there has been a steady wave of immigrants, asylum seekers and refugees…

The Society's Involvement in the Defense of Human Rights

NASA Astrophysics Data System (ADS)

Gerjuoy, Edward

2015-04-01

The history of the Society's involvement in the defense of human rights, a history of which the Society can be proud, will be summarized; the summary will include illustrative specific APS human rights defense actions in illustrative specific cases. As will be emphasized, the aforesaid involvement has been primarily through the activities of the APS Committee on International Freedom of Scientists (CIFS). It is noteworthy-and one of the reasons the Society can be proud-that CIFS is charged with ``monitoring concerns regarding human rights for scientists,'' not solely for physicists, and that CIFS indeed has sought to protect the human rights of nonphysicists.

The Na+/K+ pump is an important modulator of refractoriness and rotor dynamics in human atrial tissue.

PubMed

Sánchez, Carlos; Corrias, Alberto; Bueno-Orovio, Alfonso; Davies, Mark; Swinton, Jonathan; Jacobson, Ingemar; Laguna, Pablo; Pueyo, Esther; Rodríguez, Blanca

2012-03-01

Pharmacological treatment of atrial fibrillation (AF) exhibits limited efficacy. Further developments require a comprehensive characterization of ionic modulators of electrophysiology in human atria. Our aim is to systematically investigate the relative importance of ionic properties in modulating excitability, refractoriness, and rotor dynamics in human atria before and after AF-related electrical remodeling (AFER). Computer simulations of single cell and tissue atrial electrophysiology were conducted using two human atrial action potential (AP) models. Changes in AP, refractory period (RP), conduction velocity (CV), and rotor dynamics caused by alterations in key properties of all atrial ionic currents were characterized before and after AFER. Results show that the investigated human atrial electrophysiological properties are primarily modulated by maximal value of Na(+)/K(+) pump current (G(NaK)) as well as conductances of inward rectifier potassium current (G(K1)) and fast inward sodium current (G(Na)). G(NaK) plays a fundamental role through both electrogenic and homeostatic modulation of AP duration (APD), APD restitution, RP, and reentrant dominant frequency (DF). G(K1) controls DF through modulation of AP, APD restitution, RP, and CV. G(Na) is key in determining DF through alteration of CV and RP, particularly in AFER. Changes in ionic currents have qualitatively similar effects in control and AFER, but effects are smaller in AFER. The systematic analysis conducted in this study unravels the important role of the Na(+)/K(+) pump current in determining human atrial electrophysiology.

Effect of localizer radiograph on radiation dose associated with automatic exposure control: human cadaver and patient study.

PubMed

Singh, Sarabjeet; Petrovic, Dean; Jamnik, Ethen; Aran, Shima; Pourjabbar, Sarvenaz; Kave, Maggie L; Bradley, Stephen E; Choy, Garry; Kalra, Mannudeep K

2014-01-01

To evaluate the effect of localizing radiograph on computed tomography (CT) radiation dose associated with automatic exposure control with a human cadaver and patient study. Institutional review board approved the study with a waiver of informed consent. Two chest CT image series with fixed tube current and combined longitudinal-angular automatic exposure control (AEC) were acquired in a human cadaver (64-year-old man) after each of the 8 combinations of localizer radiographs (anteroposterior [AP], AP lateral, AP-posteroanterior [PA], lateral AP, lateral PA, PA, PA-AP, and PA lateral). Applied effective milliampere second, volume CT dose index (CTDIvol) and image noise were recorded for all 24-image series. Volume CT dose indexes were also recorded in 20 patients undergoing chest and abdominal CT after PA and PA-lateral radiographs with the use of AEC. Data were analyzed using analysis of variance and linear correlation tests. With AEC, the CTDIvol fluctuates with the number and projection of localizer radiographs (P < 0.0001). Lowest CTDIvol values are seen when 2 orthogonal localizer radiographs are acquired, whereas highest values are seen when single PA or AP-PA projection localizer radiographs are acquired for planning (P < 0.0001). In 20 patients, CT scanning with AEC after acquisition of 2 orthogonal projection localizer radiographs was associated with significant reduction in radiation dose compared to PA projection radiographs alone (P < 0.0001). When scanning with AEC, acquisition of 2 orthogonal localizer radiographs is associated with lower CTDIvol compared to a single localizer radiograph.

Effects of a human recombinant alkaline phosphatase on renal hemodynamics, oxygenation and inflammation in two models of acute kidney injury.

PubMed

Peters, Esther; Ergin, Bülent; Kandil, Asli; Gurel-Gurevin, Ebru; van Elsas, Andrea; Masereeuw, Rosalinde; Pickkers, Peter; Ince, Can

2016-12-15

Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase (AP) improves renal function in critically ill patients with sepsis-associated acute kidney injury (AKI), for which the mechanism of action is not completely understood. Here, we investigated the effects of a newly developed human recombinant AP (recAP) on renal oxygenation and hemodynamics and prevention of kidney damage and inflammation in two in vivo AKI models. To induce AKI, male Wistar rats (n=18) were subjected to renal ischemia (30min) and reperfusion (I/R), or sham-operated. In a second model, rats (n=18) received a 30min infusion of lipopolysaccharide (LPS; 2.5mg/kg), or saline, and fluid resuscitation. In both models, recAP (1000U/kg) was administered intravenously (15min before reperfusion, or 90min after LPS). Following recAP treatment, I/R-induced changes in renal blood flow, renal vascular resistance and oxygen delivery at early, and cortical microvascular oxygen tension at late reperfusion were no longer significantly affected. RecAP did not influence I/R-induced effects on mean arterial pressure. During endotoxemia, recAP treatment did not modulate the LPS-induced changes in systemic hemodynamics and renal oxygenation. In both models, recAP did exert a clear renal protective anti-inflammatory effect, demonstrated by attenuated immunostaining of inflammatory, tubular injury and pro-apoptosis markers. Whether this renal protective effect is sufficient to improve outcome of patients suffering from sepsis-associated AKI is being investigated in a large clinical trial. Copyright © 2016. Published by Elsevier Inc.

[Seed geography: its concept and basic scientific issues].

PubMed

Yu, Shun-Li; Wang, Zong-Shuai; Zeren, Wangmu

2010-01-01

In this paper, a new concept 'seed geography' was provided, and its definition, research contents, and scientific issues were put forward. Seed geography is a newly developed interdisciplinary science from plant geography, seed ecology, and phytosociology, which studies the geographic variation patterns of seed biological traits as well as their relationships with environmental factors from macroscopic to microscopic, and the seed formation, development, and change trends. The main research contents would include geography of seed mass, geography of seed chemical components, geography of seed morphology, geography of seed cell biological characteristics, geography of seed physiological characteristics, geography of seed genetic characteristics, and geography of flower and fruit. To explore the scientific issues in seed geography would help us to better understand the long-term adaptation and evolution of seed characteristics to natural environments.

Biogeography as critical nursing pedagogy: Breathing life into nurse education.

PubMed

Kyle, Richard G; Atherton, Iain M

2016-09-01

Insights from the social sciences, including geography, sociology, and anthropology, have long been incorporated into pre-registration nursing programmes. However, scholars have suggested that their inclusion has been sporadic and lacks clear theoretical rationale. In this paper we argue anew that the social sciences - and particularly, human geography - could be central to nurse education. Specifically, we recast the concept of 'biogeography' drawn from human geography that emphasises the interplay between life (bio) and place (geo) to propose pedagogy that theoretically justifies and practically enables the inclusion of the social sciences in nurse education. Biogeography can breathe new life into nursing curricula by animating our students through the cultivation of three 'spirits of nursing'. First, a 'spirit of empathy' that can shatter patient-professional dualisms by facilitating person-centred and place-sensitive care. Second, a 'spirit of engagement' that situates practice in social structures awakening a desire to effect change by fomenting an acute sense of social justice. Third, a 'spirit of enquiry' that holds in critical tension the theory-practice gap by fostering continual questioning and pursuit of evidence. In so doing, biogeographical pedagogy releases the latent potential of the social sciences to revitalise nurse education, reinvigorate our students, and renew ourselves as nurse educators. Copyright © 2016 Elsevier Ltd. All rights reserved.

The adipocyte fatty acid–binding protein aP2 is required in allergic airway inflammation

PubMed Central

Shum, Bennett O.V.; Mackay, Charles R.; Gorgun, Cem Z.; Frost, Melinda J.; Kumar, Rakesh K.; Hotamisligil, Gökhan S.; Rolph, Michael S.

2006-01-01

The adipocyte fatty acid–binding protein aP2 regulates systemic glucose and lipid metabolism. We report that aP2, in addition to being abundantly expressed by adipocytes, is also expressed by human airway epithelial cells and shows a striking upregulation following stimulation of epithelial cells with the Th2 cytokines IL-4 and IL-13. Regulation of aP2 mRNA expression by Th2 cytokines was highly dependent on STAT6, a transcription factor with a major regulatory role in allergic inflammation. We examined aP2-deficient mice in a model of allergic airway inflammation and found that infiltration of leukocytes, especially eosinophils, into the airways was highly dependent on aP2 function. T cell priming was unaffected by aP2 deficiency, suggesting that aP2 was acting locally within the lung, and analysis of bone marrow chimeras implicated non-hematopoietic cells, most likely bronchial epithelial cells, as the site of action of aP2 in allergic airway inflammation. Thus, aP2 regulates allergic airway inflammation and may provide a link between fatty acid metabolism and asthma. PMID:16841093

COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer.

PubMed

Gao, Shujun; Fang, Lekun; Phan, Liem Minh; Qdaisat, Aiham; Yeung, Sai-Ching J; Lee, Mong-Hong

2015-09-29

Cervical cancer is one of the leading causes of cancer death in women. Human papillomaviruses (HPVs) are the major cause in almost 99.7% of cervical cancer. E6 oncoprotein of HPV and E6-associated protein (E6AP) are critical in causing p53 degradation and malignancy. Understanding the E6AP regulation is critical to develop treating strategy for cervical cancer patients. The COP9 signalosome subunit 6 (CSN6) is involved in ubiquitin-mediated protein degradation. We found that both CSN6 and E6AP are overexpressed in cervical cancer. We characterized that CSN6 associated with E6AP and stabilized E6AP expression by reducing E6AP poly-ubiquitination, thereby regulating p53 activity in cell proliferation and apoptosis. Mechanistic studies revealed that CSN6-E6AP axis can be regulated by EGF/Akt signaling. Furthermore, inhibition of CSN6-E6AP axis hinders cervical cancer growth in mice. Taken together, our results indicate that CSN6 is a positive regulator of E6AP and is important for cervical cancer development.

An Analysis of Geography Content in Relation to Geography for Life Standards in Oman

ERIC Educational Resources Information Center

Al-Nofli, Mohammed Abdullah

2018-01-01

Since the publication of "Geography for Life: National Geography Standards" in the United States (Geography Education Standards Project, 1994), it has been widely used to develop quality curriculum materials for what students should know and able to do in geography. This study compared geography content taught in Omani public schools…

Our World of 7 Billion: Population Studies in Today's Social Studies Classroom

ERIC Educational Resources Information Center

Wasserman, Pamela

2011-01-01

The study of world population integrates so many themes and disciplines in the social studies because it encompasses all of human history--the rise of agriculture and civilizations, scientific progress, territorial conflicts, changing gender roles and more. It is also at the heart of human geography and how people came to dominate and alter the…

Chromosome instability on children with asthma.

PubMed

Lialiaris, Theodore; Polyzou, Aggeliki; Mpountoukas, Panagiotis; Tsiggene, Anthi; Kouskoukis, Alexandros; Pouliliou, Stamatia; Paraskakis, Emmanouil; Tentes, Ioannis; Trypsianis, Grigorios; Chatzimichail, Athanasios

2009-10-01

Asthma is a complex disease with multiple interactions between genetic and environmental factors. The aim of our study was to investigate the possible genetic instability in asthmatic patients (AP) with asthma in human cultured peripheral blood lymphocytes. Furthermore, the presence of either cytostaticity or cytotoxicity was demonstrated. Human peripheral blood lymphocytes were cultured from 18 admitted children to the Pediatric Clinic of the University Hospital of Alexandroupolis (average age 7.2 years), and 9 healthy blood donors were used as control subjects (average age 6.5 years), none of whom was receiving drugs for medical or other reasons. A significant (p < 0.05) increase in spontaneous sister chromatid exchanges (SCEs) frequency in asthmatic patients compared with control subjects was observed. No statistically significant modification in the spontaneous proliferation rate index (PRI) in AP compared with the controls was demonstrated. Finally, MMC induced a statistically significant increase in SCEs frequency both to controls and to AP, with the MMC-induced SCEs rates in AP being statistically (p < 0.01) higher compared to the MMC-induced SCEs in controls. We try to improve a new diagnostic process of possible genetic instability by a combination of genotoxic, cytostatic and cytotoxic effects of asthma on human peripheral lymphocytes.

Diadenosine polyphosphates induce intracellular Ca2+ mobilization in human neutrophils via a pertussis toxin sensitive G-protein.

PubMed Central

Gasmi, L; McLennan, A G; Edwards, S W

1997-01-01

The diadenosine polyphosphates diadenosine 5',5"'-P1,P3-triphosphate (Ap3A), diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A), diadenosine 5',5"'-P1,P5-pentaphosphate (Ap5A) and diadenosine 5',5"'-P1,P6-hexaphosphate (Ap6A) all stimulated increases in intracellular Ca2+ in human neutrophils. Maximal increases in intracellular Ca2+ of 650 nM were obtained at dinucleotide concentrations of 500-700 microM. These increases in intracellular, Ca2+ were completely abolished by pre-treatment of the neutrophils with pertussis toxin and were hardly affected when the extracellular buffer was devoid of Ca2+. On the other hand, adenosine triphosphate (ATP) could stimulate much greater increases in intracellular Ca2+ (up to 1.1 microM) at much lower concentrations (half maximal responses obtained at around 5 microM ATP). Receptor de-sensitization experiments indicate that human neutrophils may possess two types of P2-purinoceptors. The first of these may bind ATP (but not the dinucleotides) with high affinity whilst the second may bind the dinucleotides with lower affinity and also bind ATP. PMID:9038726

[Growth inhibition effection of perlecan anti-sense cDNA on human laryngeal carcinoma xnograft in nude mice].

PubMed

Chen, Guangli; Gong, Shusheng; Chen, Pei; Luo, Linghui

2014-09-01

To observe growth inhibition effect of perlecan anti-sense cDNA (pAP) on human laryngeal carcinoma xnografted in nude mice. To vertify its antitumor effect and mechanism in vivo, and it may be useful as a biomarker in carcinoma of larynx cancer. Created the model of human laryngeal carcinoma xnograft in nude mice. To observe growth of those xnografts in nude mice and draw growth curve of xnografted. The expression of perlecan mRNA and portein in xnografts were examined by RT-PCR and immunohistochemistry. Volume of xnografts in the group transfected by the plasmids of pAP were significant small as compared with other two groups made by the wild type cells and phpApr-neol cells (P < 0.05). It was showed that the expression of perlecan mRNA and protein were significantly reduced in the tumor of pAP transfected Hep-2 cells as compared with the tumors transfected by the wild type cells and phβApr-neol cells (P < 0.01). These data raise the possibility that pAP many play key roles in the growth of those xnografts in nude mice.

Cardiovascular regulation in humans in response to oscillatory lower body negative pressure

NASA Technical Reports Server (NTRS)

Levenhagen, D. K.; Evans, J. M.; Wang, M.; Knapp, C. F.

1994-01-01

The frequency response characteristics of human cardiovascular regulation during hypotensive stress have not been determined. We therefore exposed 10 male volunteers to seven frequencies (0.004-0.1 Hz) of oscillatory lower body negative pressure (OLBNP; 0-50 mmHg). Fourier spectra of arterial pressure (AP), central venous pressure (CVP), stroke volume (SV), cardiac output (CO), heart rate (HR), and total peripheral resistance (TPR) were determined and first harmonic mean, amplitude, and phase angles with respect to OLBNP are presented. AP was relatively well regulated as demonstrated by small oscillations in half amplitude (3.5 mmHg) that were independent of OLBNP frequency and similar to unstressed control spectra. Due to the biomechanics of the system, the magnitudes of oscillations in calf circumference (CC) and CVP decreased with increasing frequency; therefore, we normalized responses by these indexes of the fluid volume shifted. The ratios of oscillations in AP to oscillations in CC increased by an order of magnitude, whereas oscillations in CVP to oscillations in CC and oscillations in AP to oscillations in CVP both tripled between 0.004 and 0.1 Hz. Therefore, even though the amount of fluid shifted by OLBNP decreased with increasing frequency, the magnitude of both CVP and AP oscillations per volume of fluid shifted increased (peaking at 0.08 Hz). The phase relationships between variables, particularly the increasing lags in SV and TPR, but not CVP, indicated that efferent responses with lags of 5-6 s could account for the observed responses. We conclude that, at frequencies below 0.02 Hz, the neural system of humans functioned optimally in regulating AP; OLBNP-induced decreases in SV (by as much as 50%) were counteracted by appropriate oscillations in HR and TPR responses. As OLBNP frequency increased, SV, TPR, and HR oscillations increasingly lagged the input and became less optimally timed for AP regulation.

Induction of interleukin-8 by Naegleria fowleri lysates requires activation of extracellular signal-regulated kinase in human astroglial cells.

PubMed

Kim, Jong-Hyun; Sohn, Hae-Jin; Lee, Sang-Hee; Kwon, Daeho; Shin, Ho-Joon

2012-08-01

Naegleria fowleri is a pathogenic free-living amoeba which causes primary amoebic meningoencephalitis in humans and experimental animals. To investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astroglial cells was investigated following treatment with N. fowleri lysates. We demonstrated that N. fowleri are potent inducers for the expression of interleukin-8 (IL-8) genes in human astroglial cells which was preceded by activation of extracellular signal-regulated kinase (ERK). In addition, N. fowleri lysates induces the DNA binding activity of activator protein-1 (AP-1), an important transcription factor for IL-8 induction. The specific mitogen-activated protein kinase kinase/ERK inhibitor, U0126, blocks N. fowleri-mediated AP-1 activation and subsequent IL-8 induction. N. fowleri-induced IL-8 expression requires activation of ERK in human astroglial cells. These findings indicate that treatment of N. fowleri on human astroglial cells leads to the activation of AP-1 and subsequent expression of IL-8 which are dependent on ERK activation. These results may help understand the N. fowleri-mediated upregulation of chemokine and cytokine expression in the astroglial cells.

A phylo-functional core of gut microbiota in healthy young Chinese cohorts across lifestyles, geography and ethnicities.

PubMed

Zhang, Jiachao; Guo, Zhuang; Xue, Zhengsheng; Sun, Zhihong; Zhang, Menghui; Wang, Lifeng; Wang, Guoyang; Wang, Fang; Xu, Jie; Cao, Hongfang; Xu, Haiyan; Lv, Qiang; Zhong, Zhi; Chen, Yongfu; Qimuge, Sudu; Menghe, Bilige; Zheng, Yi; Zhao, Liping; Chen, Wei; Zhang, Heping

2015-09-01

Structural profiling of healthy human gut microbiota across heterogeneous populations is necessary for benchmarking and characterizing the potential ecosystem services provided by particular gut symbionts for maintaining the health of their hosts. Here we performed a large structural survey of fecal microbiota in 314 healthy young adults, covering 20 rural and urban cohorts from 7 ethnic groups living in 9 provinces throughout China. Canonical analysis of unweighted UniFrac principal coordinates clustered the subjects mainly by their ethnicities/geography and less so by lifestyles. Nine predominant genera, all of which are known to contain short-chain fatty acid producers, co-occurred in all individuals and collectively represented nearly half of the total sequences. Interestingly, species-level compositional profiles within these nine genera still discriminated the subjects according to their ethnicities/geography and lifestyles. Therefore, a phylogenetically diverse core of gut microbiota at the genus level may be commonly shared by distinctive healthy populations as functionally indispensable ecosystem service providers for the hosts.

A phylo-functional core of gut microbiota in healthy young Chinese cohorts across lifestyles, geography and ethnicities

PubMed Central

Zhang, Jiachao; Guo, Zhuang; Xue, Zhengsheng; Sun, Zhihong; Zhang, Menghui; Wang, Lifeng; Wang, Guoyang; Wang, Fang; Xu, Jie; Cao, Hongfang; Xu, Haiyan; Lv, Qiang; Zhong, Zhi; Chen, Yongfu; Qimuge, Sudu; Menghe, Bilige; Zheng, Yi; Zhao, Liping; Chen, Wei; Zhang, Heping

2015-01-01

Structural profiling of healthy human gut microbiota across heterogeneous populations is necessary for benchmarking and characterizing the potential ecosystem services provided by particular gut symbionts for maintaining the health of their hosts. Here we performed a large structural survey of fecal microbiota in 314 healthy young adults, covering 20 rural and urban cohorts from 7 ethnic groups living in 9 provinces throughout China. Canonical analysis of unweighted UniFrac principal coordinates clustered the subjects mainly by their ethnicities/geography and less so by lifestyles. Nine predominant genera, all of which are known to contain short-chain fatty acid producers, co-occurred in all individuals and collectively represented nearly half of the total sequences. Interestingly, species-level compositional profiles within these nine genera still discriminated the subjects according to their ethnicities/geography and lifestyles. Therefore, a phylogenetically diverse core of gut microbiota at the genus level may be commonly shared by distinctive healthy populations as functionally indispensable ecosystem service providers for the hosts. PMID:25647347

Role of adaptor proteins and clathrin in the trafficking of human kidney anion exchanger 1 (kAE1) to the cell surface.

PubMed

Junking, Mutita; Sawasdee, Nunghathai; Duangtum, Natapol; Cheunsuchon, Boonyarit; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-thai

2014-07-01

Kidney anion exchanger 1 (kAE1) plays an important role in acid-base homeostasis by mediating chloride/bicarbornate (Cl-/HCO3-) exchange at the basolateral membrane of α-intercalated cells in the distal nephron. Impaired intracellular trafficking of kAE1 caused by mutations of SLC4A1 encoding kAE1 results in kidney disease - distal renal tubular acidosis (dRTA). However, it is not known how the intracellular sorting and trafficking of kAE1 from trans-Golgi network (TGN) to the basolateral membrane occurs. Here, we studied the role of basolateral-related sorting proteins, including the mu1 subunit of adaptor protein (AP) complexes, clathrin and protein kinase D, on kAE1 trafficking in polarized and non-polarized kidney cells. By using RNA interference, co-immunoprecipitation, yellow fluorescent protein-based protein fragment complementation assays and immunofluorescence staining, we demonstrated that AP-1 mu1A, AP-3 mu1, AP-4 mu1 and clathrin (but not AP-1 mu1B, PKD1 or PKD2) play crucial roles in intracellular sorting and trafficking of kAE1. We also demonstrated colocalization of kAE1 and basolateral-related sorting proteins in human kidney tissues by double immunofluorescence staining. These findings indicate that AP-1 mu1A, AP-3 mu1, AP-4 mu1 and clathrin are required for kAE1 sorting and trafficking from TGN to the basolateral membrane of acid-secreting α-intercalated cells. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fibroblast growth factor 2 regulates bone sialoprotein gene transcription in human breast cancer cells.

PubMed

Li, Zhengyang; Wang, Zhitao; Yang, Li; Li, Xinyue; Sasaki, Yoko; Wang, Shuang; Araki, Shouta; Mezawa, Masaru; Takai, Hideki; Nakayama, Youhei; Ogata, Yorimasa

2010-03-01

Bone sialoprotein (BSP) is a major non-collagenous, extracellular matrix glycoprotein associated with mineralized tissues. Fibroblast growth factor 2 (FGF2) is recognized as a potent mitogen for a variety of mesenchymal cells. FGF2 produced by osteoblasts accumulates in the bone matrix and acts as an autocrine/paracrine regulator of osteoblasts. We previously reported that FGF2 regulates BSP gene transcription through the FGF2 response element (FRE) and activator protein 1 (AP1) binding site overlapping with the glucocorticoid response element in the rat BSP gene promoter. In the present study, FGF2 (10 ng/ml) increased BSP and Runx2 mRNA levels at 6 h in MCF7 human breast cancer cells. Transient transfection analyses were performed using chimeric constructs of the human BSP gene promoter linked to a luciferase reporter gene. Treatment of MCF7 cells with FGF2 (10 ng/ml) increased the luciferase activity of the constructs between -84LUC and -927LUC. Gel mobility shift analyses showed that FGF2 increased the binding of AP1 and CRE2. The CRE2- and AP1-protein complexes were disrupted by antibodies against CREB1, c-Fos, c-Jun, Fra2, p300 and Runx2. These studies demonstrate that FGF2 stimulates BSP transcription in MCF7 human breast cancer cells by targeting the AP1 and CRE2 elements in the human BSP gene promoter.

Matrix proteins of Nipah and Hendra viruses interact with beta subunits of AP-3 complexes.

PubMed

Sun, Weina; McCrory, Thomas S; Khaw, Wei Young; Petzing, Stephanie; Myers, Terrell; Schmitt, Anthony P

2014-11-01

Paramyxoviruses and other negative-strand RNA viruses encode matrix proteins that coordinate the virus assembly process. The matrix proteins link the viral glycoproteins and the viral ribonucleoproteins at virus assembly sites and often recruit host machinery that facilitates the budding process. Using a co-affinity purification strategy, we have identified the beta subunit of the AP-3 adapter protein complex, AP3B1, as a binding partner for the M proteins of the zoonotic paramyxoviruses Nipah virus and Hendra virus. Binding function was localized to the serine-rich and acidic Hinge domain of AP3B1, and a 29-amino-acid Hinge-derived polypeptide was sufficient for M protein binding in coimmunoprecipitation assays. Virus-like particle (VLP) production assays were used to assess the relationship between AP3B1 binding and M protein function. We found that for both Nipah virus and Hendra virus, M protein expression in the absence of any other viral proteins led to the efficient production of VLPs in transfected cells, and this VLP production was potently inhibited upon overexpression of short M-binding polypeptides derived from the Hinge region of AP3B1. Both human and bat (Pteropus alecto) AP3B1-derived polypeptides were highly effective at inhibiting the production of VLPs. VLP production was also impaired through small interfering RNA (siRNA)-mediated depletion of AP3B1 from cells. These findings suggest that AP-3-directed trafficking processes are important for henipavirus particle production and identify a new host protein-virus protein binding interface that could become a useful target in future efforts to develop small molecule inhibitors to combat paramyxoviral infections. Henipaviruses cause deadly infections in humans, with a mortality rate of about 40%. Hendra virus outbreaks in Australia, all involving horses and some involving transmission to humans, have been a continuing problem. Nipah virus caused a large outbreak in Malaysia in 1998, killing 109 people, and smaller outbreaks have since occurred in Bangladesh and India. In this study, we have defined, for the first time, host factors that interact with henipavirus M proteins and contribute to viral particle assembly. We have also defined a new host protein-viral protein binding interface that can potentially be targeted for the inhibition of paramyxovirus infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Matrix Proteins of Nipah and Hendra Viruses Interact with Beta Subunits of AP-3 Complexes

PubMed Central

Sun, Weina; McCrory, Thomas S.; Khaw, Wei Young; Petzing, Stephanie; Myers, Terrell

2014-01-01

ABSTRACT Paramyxoviruses and other negative-strand RNA viruses encode matrix proteins that coordinate the virus assembly process. The matrix proteins link the viral glycoproteins and the viral ribonucleoproteins at virus assembly sites and often recruit host machinery that facilitates the budding process. Using a co-affinity purification strategy, we have identified the beta subunit of the AP-3 adapter protein complex, AP3B1, as a binding partner for the M proteins of the zoonotic paramyxoviruses Nipah virus and Hendra virus. Binding function was localized to the serine-rich and acidic Hinge domain of AP3B1, and a 29-amino-acid Hinge-derived polypeptide was sufficient for M protein binding in coimmunoprecipitation assays. Virus-like particle (VLP) production assays were used to assess the relationship between AP3B1 binding and M protein function. We found that for both Nipah virus and Hendra virus, M protein expression in the absence of any other viral proteins led to the efficient production of VLPs in transfected cells, and this VLP production was potently inhibited upon overexpression of short M-binding polypeptides derived from the Hinge region of AP3B1. Both human and bat (Pteropus alecto) AP3B1-derived polypeptides were highly effective at inhibiting the production of VLPs. VLP production was also impaired through small interfering RNA (siRNA)-mediated depletion of AP3B1 from cells. These findings suggest that AP-3-directed trafficking processes are important for henipavirus particle production and identify a new host protein-virus protein binding interface that could become a useful target in future efforts to develop small molecule inhibitors to combat paramyxoviral infections. IMPORTANCE Henipaviruses cause deadly infections in humans, with a mortality rate of about 40%. Hendra virus outbreaks in Australia, all involving horses and some involving transmission to humans, have been a continuing problem. Nipah virus caused a large outbreak in Malaysia in 1998, killing 109 people, and smaller outbreaks have since occurred in Bangladesh and India. In this study, we have defined, for the first time, host factors that interact with henipavirus M proteins and contribute to viral particle assembly. We have also defined a new host protein-viral protein binding interface that can potentially be targeted for the inhibition of paramyxovirus infections. PMID:25210190

The absorption and transport of magnolol in Caco-2 cell model.

PubMed

Wu, An-Guo; Zeng, Bao; Huang, Meng-Qiu; Li, Sheng-Mei; Chen, Jian-Nan; Lai, Xiao-Ping

2013-03-01

To investigate the absorption and transport mechanism of magnolol in Caco-2 cell model. A human intestinal epithelial cell model Caco-2 cell in vitro cultured was applied to study the absorption and transport of magnolol, the effects of time, donor concentration, P-gp inhibitor verapamil, pH and temperature on the absorption and transport of magnolol were investigated. The determination of magnolol was performed by high performance liquid chromatography, then the values of apparent permeability coefficient (P app ) and P ratio Basolateral-to-Apical (BL-to-AP)/Apical-to-Basolateral (AP-to-BL) were calculated. In Caco-2 cell model, comparing the amounts of transport of AP-to-BL and BL-to-AP, the latter was larger. At the same donor concentration, either the amounts of transport of AP-to-BL or BL-to-AP increased with increase in donor concentration and incubation time. Verapamil could significantly improve the amounts of transport of AP-to-BL. The transport of AP-to-BL and BL-to-AP depended on temperature, and there was no significant effect of pH on the transport of AP-to-BL. Magnolol could be transported through the intestinal mucosa via a passive diffusion mechanism primarily, coexisting with a carrier-mediated transport, at the same time, the efflux mechanism could be involved.

AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking

PubMed Central

Setta-Kaffetzi, Niovi; Simpson, Michael A.; Navarini, Alexander A.; Patel, Varsha M.; Lu, Hui-Chun; Allen, Michael H.; Duckworth, Michael; Bachelez, Hervé; Burden, A. David; Choon, Siew-Eng; Griffiths, Christopher E.M.; Kirby, Brian; Kolios, Antonios; Seyger, Marieke M.B.; Prins, Christa; Smahi, Asma; Trembath, Richard C.; Fraternali, Franca; Smith, Catherine H.; Barker, Jonathan N.; Capon, Francesca

2014-01-01

Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis. PMID:24791904

TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells.

PubMed

Patel, Devang N; Bailey, Steven R; Gresham, John K; Schuchman, David B; Shelhamer, James H; Goldstein, Barry J; Foxwell, Brian M; Stemerman, Michael B; Maranchie, Jodi K; Valente, Anthony J; Mummidi, Srinivas; Chandrasekar, Bysani

2006-09-08

CXCL16 is a transmembrane non-ELR CXC chemokine that signals via CXCR6 to induce aortic smooth muscle cell (ASMC) proliferation. While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known. Here, we demonstrate that LPS upregulates CXCR6 mRNA, protein, and surface expression in human ASMC. Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-kappaB (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression. Using dominant negative expression vectors and siRNA interference, we demonstrate that LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways. Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS-mediated AP-1-dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA. Finally, CXCR6 knockdown inhibited CXCL16-induced ASMC proliferation. These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis.

TLR4-NOX4-AP-1 signaling mediates lipopolysaccharide-induced CXCR6 expression in human aortic smooth muscle cells

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

Patel, Devang N.; Bailey, Steven R.; Gresham, John K.

2006-09-08

CXCL16 is a transmembrane non-ELR CXC chemokine that signals via CXCR6 to induce aortic smooth muscle cell (ASMC) proliferation. While bacterial lipopolysaccharide (LPS) has been shown to stimulate CXCL16 expression in SMC, its effects on CXCR6 are not known. Here, we demonstrate that LPS upregulates CXCR6 mRNA, protein, and surface expression in human ASMC. Inhibition of TLR4 with neutralizing antibodies or specific siRNA interference blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-{kappa}B (p50 and p65) activation, but only inhibition of AP-1 attenuated LPS-induced CXCR6 expression. Using dominant negative expression vectors and siRNA interference, we demonstrate thatmore » LPS induces AP-1 activation via MyD88, TRAF6, ERK1/2, and JNK signaling pathways. Furthermore, the flavoprotein inhibitor diphenyleniodonium chloride significantly attenuated LPS-mediated AP-1-dependent CXCR6 expression, as did inhibition of NOX4 NADPH oxidase by siRNA. Finally, CXCR6 knockdown inhibited CXCL16-induced ASMC proliferation. These results demonstrate that LPS-TLR4-NOX4-AP-1 signaling can induce CXCR6 expression in ASMC, and suggest that the CXCL16-CXCR6 axis may be an important proinflammatory pathway in the pathogenesis of atherosclerosis.« less

Human acylphosphatase cannot replace phosphoglycerate kinase in Saccharomyces cerevisiae.

PubMed

Van Hoek, P; Modesti, A; Ramponi, G; Kötter, P; van Dijken, J P; Pron, J T

2001-10-01

Human acylphosphatase (h-AP, EC 3.6.1.7) has been reported to catalyse the hydrolysis of the 1-phosphate group of 1,3-diphosphoglycerate. In vivo operation of this reaction in the yeast Saccharomyces cerevisiae would bypass phosphoglycerate kinase and thus reduce the ATP yield from glycolysis. To investigate whether h-AP can indeed replace the S. cerevisiae phosphoglycerate kinase, a multi-copy plasmid carrying the h-AP gene under control of the yeast TDH3 promoter was introduced into a pgk1 delta mutant of S. cerevisiae. A strain carrying the expression vector without the h-AP cassette was used as a reference. For both strains, steady-state carbon- and energy-limited chemostat cultures were obtained at a dilution rate of 0.10 h(-1) on a medium containing a mixture of glucose and ethanol (15% and 85% on a carbon basis, respectively). Although the h-AP strain exhibited a high acylphosphatase activity in cell extracts, switching to glucose as sole carbon and energy source resulted in a complete arrest of glucose consumption and growth. The lack of a functional glycolytic pathway was further evident from the absence of ethanol formation in the presence of excess glucose in the culture. As h-AP cannot replace yeast phosphoglycerate kinase in vivo, the enzyme is not a useful tool to modify the ATP yield of glycolysis in S. cerevisiae.

Role of ubiquitin and the HPV E6 oncoprotein in E6AP-mediated ubiquitination

PubMed Central

Mortensen, Franziska; Schneider, Daniel; Barbic, Tanja; Sladewska-Marquardt, Anna; Kühnle, Simone; Marx, Andreas; Scheffner, Martin

2015-01-01

Deregulation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with three different clinical pictures. Hijacking of E6AP by the E6 oncoprotein of distinct human papillomaviruses (HPV) contributes to the development of cervical cancer, whereas loss of E6AP expression or function is the cause of Angelman syndrome, a neurodevelopmental disorder, and increased expression of E6AP has been involved in autism spectrum disorders. Although these observations indicate that the activity of E6AP has to be tightly controlled, only little is known about how E6AP is regulated at the posttranslational level. Here, we provide evidence that the hydrophobic patch of ubiquitin comprising Leu-8 and Ile-44 is important for E6AP-mediated ubiquitination, whereas it does not affect the catalytic properties of the isolated catalytic HECT domain of E6AP. Furthermore, we show that the HPV E6 oncoprotein rescues the disability of full-length E6AP to use a respective hydrophobic patch mutant of ubiquitin for ubiquitination and that it stimulates E6AP-mediated ubiquitination of Ring1B, a known substrate of E6AP, in vitro and in cells. Based on these data, we propose that E6AP exists in at least two different states, an active and a less active or latent one, and that the activity of E6AP is controlled by noncovalent interactions with ubiquitin and allosteric activators such as the HPV E6 oncoprotein. PMID:26216987

Mechanisms of pro-arrhythmic abnormalities in ventricular repolarisation and anti-arrhythmic therapies in human hypertrophic cardiomyopathy.

PubMed

Passini, Elisa; Mincholé, Ana; Coppini, Raffaele; Cerbai, Elisabetta; Rodriguez, Blanca; Severi, Stefano; Bueno-Orovio, Alfonso

2016-07-01

Hypertrophic cardiomyopathy (HCM) is a cause of sudden arrhythmic death, but the understanding of its pro-arrhythmic mechanisms and an effective pharmacological treatment are lacking. HCM electrophysiological remodelling includes both increased inward and reduced outward currents, but their role in promoting repolarisation abnormalities remains unknown. The goal of this study is to identify key ionic mechanisms driving repolarisation abnormalities in human HCM, and to evaluate anti-arrhythmic effects of single and multichannel inward current blocks. Experimental ionic current, action potential (AP) and Ca(2+)-transient (CaT) recordings were used to construct populations of human non-diseased and HCM AP models (n=9118), accounting for inter-subject variability. Simulations were conducted for several degrees of selective and combined inward current block. Simulated HCM cardiomyocytes exhibited prolonged AP and CaT, diastolic Ca(2+) overload and decreased CaT amplitude, in agreement with experiments. Repolarisation abnormalities in HCM models were consistently driven by L-type Ca(2+) current (ICaL) re-activation, and ICaL block was the most effective intervention to normalise repolarisation and diastolic Ca(2+), but compromised CaT amplitude. Late Na(+) current (INaL) block partially abolished repolarisation abnormalities, with small impact on CaT. Na(+)/Ca(2+) exchanger (INCX) block effectively restored repolarisation and CaT amplitude, but increased Ca(2+) overload. Multichannel block increased efficacy in normalising repolarisation, AP biomarkers and CaT amplitude compared to selective block. Experimentally-calibrated populations of human AP models identify ICaL re-activation as the key mechanism for repolarisation abnormalities in HCM, and combined INCX, INaL and ICaL block as effective anti-arrhythmic therapies also able to partially reverse the HCM electrophysiological phenotype. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

ERalpha and AP-1 interact in vivo with a specific sequence of the F promoter of the human ERalpha gene in osteoblasts.

PubMed

Lambertini, Elisabetta; Tavanti, Elisa; Torreggiani, Elena; Penolazzi, Letizia; Gambari, Roberto; Piva, Roberta

2008-07-01

Estrogen-responsive genes often have an estrogen response element (ERE) positioned next to activator protein-1 (AP-1) binding sites. Considering that the interaction between ERE and AP-1 elements has been described for the modulation of bone-specific genes, we investigated the 17-beta-estradiol responsiveness and the role of these cis-elements present in the F promoter of the human estrogen receptor alpha (ERalpha) gene. The F promoter, containing the sequence analyzed here, is one of the multiple promoters of the human ERalpha gene and is the only active promoter in bone tissue. Through electrophoretic mobility shift (EMSA), chromatin immunoprecipitation (ChIP), and re-ChIP assays, we investigated the binding of ERalpha and four members of the AP-1 family (c-Jun, c-fos, Fra-2, and ATF2) to a region located approximately 800 bp upstream of the transcriptional start site of exon F of the human ERalpha gene in SaOS-2 osteoblast-like cells. Reporter gene assay experiments in combination with DNA binding assays demonstrated that F promoter activity is under the control of upstream cis-acting elements which are recognized by specific combinations of ERalpha, c-Jun, c-fos, and ATF2 homo- and heterodimers. Moreover, ChIP and re-ChIP experiments showed that these nuclear factors bind the F promoter in vivo with a simultaneous occupancy stimulated by 17-beta-estradiol. Taken together, our findings support a model in which ERalpha/AP-1 complexes modulate F promoter activity under conditions of 17-beta-estradiol stimulation. (c) 2008 Wiley-Liss, Inc.

Czech Student Attitudes towards Geography

ERIC Educational Resources Information Center

Kubiatko, Milan; Janko, Tomas; Mrazkova, Katerina

2012-01-01

This study investigates 540 Czech lower secondary students' attitudes towards geography. It examined the general influence of gender and grade level on attitudes towards geography with an emphasis on four specific areas in particular: geography as a school subject; geography and the environment; the importance of geography; and the relevance of…

Tricyclic coumarin sulphonate derivatives with alkaline phosphatase inhibitory effects: in vitro and docking studies.

PubMed

Iqbal, Jamshed; El-Gamal, Mohammed I; Ejaz, Syeda Abida; Lecka, Joanna; Sévigny, Jean; Oh, Chang-Hyun

2018-12-01

Tissue-nonspecific alkaline phosphatase (TNAP) is an important isozyme of alkaline phosphatases, which plays different pivotal roles within the human body. Most importantly, it is responsible for maintaining the balanced ratio of phosphate and inorganic pyrophosphate, thus regulates the extracellular matrix calcification during bone formation and growth. The elevated level of TNAP has been linked to vascular calcification and end-stage renal diseases. Consequently, there is a need to search for highly potent and selective inhibitors of alkaline phosphatases (APs) for treatment of disorders associated with the over-expression of APs. Herein, a series of tricyclic coumarin sulphonate 1a-za with known antiproliferative activity, was evaluated for AP inhibition against human tissue nonspecific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP). The methylbenzenesulphonate derivative 1f (IC 50  = 0.38 ± 0.01 μM) was found to be the most active h-TNAP inhibitor. Another 4-fluorobenzenesulphonate derivative 1i (IC 50  = 0.45 ± 0.02 μM) was found as the strongest inhibitor of h-IAP. Some of the derivatives were also identified as highly selective inhibitors of APs. Detailed structure-activity relationship (SAR) was investigated to identify the functional groups responsible for the effective inhibition of AP isozymes. The study was also supported by the docking studies to rationalise the most possible binding site interactions of the identified inhibitors with the targeted enzymes.

Biology of Skin Color.

ERIC Educational Resources Information Center

Corcos, Alain

1983-01-01

Information from scientific journals on the biology of skin color is discussed. Major areas addressed include: (1) biology of melanin, melanocytes, and melanosomes; (2) melanosome and human diversity; (3) genetics of skin color; and (4) skin color, geography, and natural selection. (JN)

GEOGRAPHY AND ENVIRONMENTAL PROTECTION AGENCY

EPA Science Inventory

The US Environmental Protection Agency helps state and local governments protect the environment by encouraging good environmental management and by regulating human activities to ensure clean air and water. At the Corvallis research laboratory for the EPA, we improve the ways t...

The augmented anticancer potential of AP9-cd loaded solid lipid nanoparticles in human leukemia Molt-4 cells and experimental tumor.

PubMed

Bhushan, Shashi; Kakkar, Vandita; Pal, Harish Chandra; Mondhe, D M; Kaur, Indu Pal

2016-01-25

AP9-cd, a novel lignan composition from Cedrus deodara has significant anticancer potential, and to further enhance its activity, it was lucratively encumbered into solid lipid nanoparticles (SLNs). These nanoparticles were formulated by micro-emulsion technique with 70% drug trap competence. AP9-cd-SLNs were regular, solid, globular particles in the range of 100-200 nm, which were confirmed by electron microscopic studies. Moreover, AP9-cd-SLNs were found to be stable for up to six months in terms of color, particle size, zeta potential, drug content and entrapment. AP9-cd-SLNs have 30-50% higher cytotoxic and apoptotic potential than the AP9-cd alone. The augmented anticancer potential of AP9-cd-SLNs was observed in cytotoxic IC50 value, apoptosis signaling cascade and in Ehrlich ascites tumor (EAT) model. AP9-cd-SLNs induce apoptosis in Molt-4 cells via both intrinsic and extrinsic pathway. Moreover, the dummy nanoparticles (SLNs without AP9-cd) did not have any cytotoxic effect in cancer as well as in normal cells. Consequently, SLNs of AP9-cd significantly augment the apoptotic and antitumor potential of AP9-cd. The present study provides a podium for ornamental the remedial latent via novel delivery systems like solid lipid nanoparticles. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Andrographis paniculata elicits anti-invasion activities by suppressing TM4SF3 gene expression and by anoikis-sensitization in esophageal cancer cells

PubMed Central

Yue, Grace Gar-Lee; Lee, Julia Kin-Ming; Li, Lin; Chan, Kar-Man; Wong, Eric Chun-Wai; Chan, Judy Yuet-Wah; Fung, Kwok-Pui; Lui, Vivian Wai Yan; Chiu, Philip Wai-Yan; Lau, Clara Bik-San

2015-01-01

Esophageal cancer is the sixth most common cancer in male causing death worldwide. It is usually diagnosed at advanced stage with high postoperative recurrence and systemic metastasis, which leads to poor prognosis. The potential inhibitory effect of herbal medicines on metastasis of esophageal cancer has drawn researchers’ great attention. In the present study, the anti-invasion activities of Andrographis paniculata (AP) have been evaluated in two esophageal cancer cell lines, EC-109 and KYSE-520, as well as human microvascular endothelial cells (HMEC-1). The anti-tumor and anti-metastatic activities of AP were also evaluated in human esophageal xenograft-bearing mouse models. Our results demonstrated for the first time that aqueous extract of AP inhibited the motility and invasion of esophageal cancer cells, which is the initial step of metastasis, without cytotoxicity. Anoikis resistance has also been reversed in AP-treated cancer cells. Besides, the expression of metastasis-related gene TM4SF3 in EC-109 cells was significantly decreased in AP extract-treated cells in a concentration-dependent manner. Furthermore, the anti-tumor and anti-metastatic efficacies in subcutaneous and intraperitoneal esophageal xenograft-bearing mice were demonstrated after oral administration of AP aqueous extract for 3 weeks. Last but not least, the active component, isoandrographolide, responsible for the anti-migratory activity was firstly revealed here. In conclusion, the AP aqueous extract exerted inhibitory activities on the migration and anoikis resistance of esophageal cancer cells EC-109 and KYSE-520, as well as suppressed the proliferation and motility of endothelial cells. Combining the mentioned effects may account for the anti-tumor and anti-metastasis effects of AP aqueous extract in xenograft-bearing mice. The findings in the present study further enhance the understanding of the therapeutic mechanisms of the herb AP, which may lead to clinical applications. PMID:26885447

Integrating Stakeholders and Users into the Geography Discipline's Research Process

USGS Publications Warehouse

Hermans, Caroline M.; Taketa, Richard

2006-01-01

Future research priorities of Geography emphasize the discipline's leadership role in the U.S. Geological Survey (USGS) in multidisciplinary and integrated research on human and environmental systems and how these systems are interrelated and respond to change Geography's research priorities also emphasize providing science that is usable to society and creating decision support products applicable to given customer problems. To achieve these goals, we must understand the relationship between our research and our customer, and how to integrate the customer into the research process. This report details the elements of the research process that help achieve the degree of stakeholder involvement necessary to ensure a successful end-product. It offers suggestions that can help researchers better understand stakeholders and customers and involve them in the research process more effectively, while preserving the integrity of the science. Its aim is to help researchers understand the problems and challenges faced by our customers and communicate the ways in which Geography can help address their problems. Adopting these guidelines can improve the efficiency of the research process and lead to higher quality output. We will be able to conduct better research because we will have an improved understanding of the research problem and the stakeholders involved. This report covers a broad range of topics, from identifying and communicating with stakeholders and users, to the use of language, to how to effectively present scientific information to the user. It does not offer a 'one size fits all' method. Instead, perhaps only specific sections are suitable for a given project and customers, depending on project scope and needs. This report is based on the objectives of Geography's strategic plan, U. S. Geological Survey's strategic plan, and Department of Interior's strategic plan. Section 2 of these guidelines describes the purpose of the research process in Geography and the need for better user involvement in the process. Section 3 explains how to conduct a stakeholder analysis. Section 4 explains how to conduct a user-needs assessment.

Patch-Clamp Recording from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Improving Action Potential Characteristics through Dynamic Clamp

PubMed Central

Veerman, Christiaan C.; Zegers, Jan G.; Mengarelli, Isabella; Bezzina, Connie R.

2017-01-01

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for studying inherited cardiac arrhythmias and developing drug therapies to treat such arrhythmias. Unfortunately, until now, action potential (AP) measurements in hiPSC-CMs have been hampered by the virtual absence of the inward rectifier potassium current (IK1) in hiPSC-CMs, resulting in spontaneous activity and altered function of various depolarising and repolarising membrane currents. We assessed whether AP measurements in “ventricular-like” and “atrial-like” hiPSC-CMs could be improved through a simple, highly reproducible dynamic clamp approach to provide these cells with a substantial IK1 (computed in real time according to the actual membrane potential and injected through the patch-clamp pipette). APs were measured at 1 Hz using perforated patch-clamp methodology, both in control cells and in cells treated with all-trans retinoic acid (RA) during the differentiation process to increase the number of cells with atrial-like APs. RA-treated hiPSC-CMs displayed shorter APs than control hiPSC-CMs and this phenotype became more prominent upon addition of synthetic IK1 through dynamic clamp. Furthermore, the variability of several AP parameters decreased upon IK1 injection. Computer simulations with models of ventricular-like and atrial-like hiPSC-CMs demonstrated the importance of selecting an appropriate synthetic IK1. In conclusion, the dynamic clamp-based approach of IK1 injection has broad applicability for detailed AP measurements in hiPSC-CMs. PMID:28867785

Pre-steady-state fluorescence analysis of damaged DNA transfer from human DNA glycosylases to AP endonuclease APE1.

PubMed

Kuznetsova, Alexandra A; Kuznetsov, Nikita A; Ishchenko, Alexander A; Saparbaev, Murat K; Fedorova, Olga S

2014-10-01

DNA glycosylases remove the modified, damaged or mismatched bases from the DNA by hydrolyzing the N-glycosidic bonds. Some enzymes can further catalyze the incision of a resulting abasic (apurinic/apyrimidinic, AP) site through β- or β,δ-elimination mechanisms. In most cases, the incision reaction of the AP-site is catalyzed by special enzymes called AP-endonucleases. Here, we report the kinetic analysis of the mechanisms of modified DNA transfer from some DNA glycosylases to the AP endonuclease, APE1. The modified DNA contained the tetrahydrofurane residue (F), the analogue of the AP-site. DNA glycosylases AAG, OGG1, NEIL1, MBD4(cat) and UNG from different structural superfamilies were used. We found that all DNA glycosylases may utilise direct protein-protein interactions in the transient ternary complex for the transfer of the AP-containing DNA strand to APE1. We hypothesize a fast "flip-flop" exchange mechanism of damaged and undamaged DNA strands within this complex for monofunctional DNA glycosylases like MBD4(cat), AAG and UNG. Bifunctional DNA glycosylase NEIL1 creates tightly specific complex with DNA containing F-site thereby efficiently competing with APE1. Whereas APE1 fast displaces other bifunctional DNA glycosylase OGG1 on F-site thereby induces its shifts to undamaged DNA regions. Kinetic analysis of the transfer of DNA between human DNA glycosylases and APE1 allows us to elucidate the critical step in the base excision repair pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluating the Geography Curriculum. Geography for Teachers Series.

ERIC Educational Resources Information Center

Marsden W. E.

The book relates rational curriculum planning to the field of geography. Intended as an aid to geography teachers and teachers in training as they reconstruct geography syllabi, the book emphasizes the need to evaluate what goes into as well as what comes out of the geography curriculum. Section I identifies aims and objectives of geographic…

Geographical Applications of Remote Sensing

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

Weng, Qihao; Zhou, Yuyu; Quattrochi, Dale

2013-02-28

Data and Information derived through Earth observation technology have been extensively used in geographic studies, such as in the areas of natural and human environments, resources, land use and land cover, human-environment interactions, and socioeconomic issues. Land-use and land-cover change (LULCC), affecting biodiversity, climate change, watershed hydrology, and other surface processes, is one of the most important research topics in geography.

ATP6AP2 over-expression causes morphological alterations in the hippocampus and in hippocampus-related behaviour.

PubMed

Bracke, A; Schäfer, S; von Bohlen Und Halbach, V; Klempin, F; Bente, K; Bracke, K; Staar, D; van den Brandt, J; Harzsch, S; Bader, M; Wenzel, U O; Peters, J; von Bohlen Und Halbach, O

2018-02-23

The (pro)renin receptor [(P)RR], also known as ATP6AP2 [ATPase 6 accessory protein 2], is highly expressed in the brain. ATP6AP2 plays a role in early brain development, adult hippocampal neurogenesis and in cognitive functions. Lack of ATP6AP2 has deleterious effects, and mutations of ATP6AP2 in humans are associated with, e.g. X-linked intellectual disability. However, little is known about the effects of over-expression of ATP6AP2 in the adult brain. We hypothesized that mice over-expressing ATP6AP2 in the brain might exhibit altered neuroanatomical features and behavioural responses. To this end, we investigated heterozygous transgenic female mice and confirmed increased levels of ATP6AP2 in the brain. Our data show that over-expression of ATP6AP2 does not affect adult hippocampal neurogenesis, exercise-induced cell proliferation, or dendritic spine densities in the hippocampus. Only a reduced ventricular volume on the gross morphological level was found. However, ATP6AP2 over-expressing mice displayed altered exploratory behaviour with respect to the hole-board and novel object recognition tests. Moreover, primary adult hippocampal neural stem cells over-expressing ATP6AP2 exhibit a faster cell cycle progression and increased cell proliferation. Together, in contrast to the known deleterious effects of ATP6AP2 depletion, a moderate over-expression results in moderate behavioural changes and affects cell proliferation rate in vitro.

Novel humic acid-bonded magnetite nanoparticles for protein immobilization.

PubMed

Bayrakci, Mevlut; Gezici, Orhan; Bas, Salih Zeki; Ozmen, Mustafa; Maltas, Esra

2014-09-01

The present paper is the first report that introduces (i) a useful methodology for chemical immobilization of humic acid (HA) to aminopropyltriethoxysilane-functionalized magnetite iron oxide nanoparticles (APS-MNPs) and (ii) human serum albumin (HSA) binding to the obtained material (HA-APS-MNPs). The newly prepared magnetite nanoparticle was characterized by using Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and elemental analysis. Results indicated that surface modification of the bare magnetite nanoparticles (MNPs) with aminopropyltriethoxysilane (APS) and HA was successfully performed. The protein binding studies that were evaluated in batch mode exhibited that HA-APS-MNPs could be efficiently used as a substrate for the binding of HSA from aqueous solutions. Usually, recovery values higher than 90% were found to be feasible by HA-APS-MNPs, while that value was around 2% and 70% in the cases of MNPs and APS-MNPs, respectively. Hence, the capacity of MNPs was found to be significantly improved by immobilization of HA. Furthermore, thermal degradation of HA-APS-MNPs and HSA bonded HA-APS-MNPs was evaluated in terms of the Horowitz-Metzger equation in order to determine kinetic parameters for thermal decomposition. Activation energies calculated for HA-APS-MNPs (20.74 kJmol(-1)) and HSA bonded HA-APS-MNPs (33.42 kJmol(-1)) implied chemical immobilization of HA to APS-MNPs, and tight interactions between HA and HA-APS-MNPs. Copyright © 2014 Elsevier B.V. All rights reserved.

"Publish or Perish" as citation metrics used to analyze scientific output in the humanities: International case studies in economics, geography, social sciences, philosophy, and history.

PubMed

Baneyx, Audrey

2008-01-01

Traditionally, the most commonly used source of bibliometric data is the Thomson ISI Web of Knowledge, in particular the (Social) Science Citation Index and the Journal Citation Reports, which provide the yearly Journal Impact Factors. This database used for the evaluation of researchers is not advantageous in the humanities, mainly because books, conference papers, and non-English journals, which are an important part of scientific activity, are not (well) covered. This paper presents the use of an alternative source of data, Google Scholar, and its benefits in calculating citation metrics in the humanities. Because of its broader range of data sources, the use of Google Scholar generally results in more comprehensive citation coverage in the humanities. This presentation compares and analyzes some international case studies with ISI Web of Knowledge and Google Scholar. The fields of economics, geography, social sciences, philosophy, and history are focused on to illustrate the differences of results between these two databases. To search for relevant publications in the Google Scholar database, the use of "Publish or Perish" and of CleanPoP, which the author developed to clean the results, are compared.

The Built Environment Is a Microbial Wasteland

PubMed Central

2016-01-01

ABSTRACT Humanity’s transition from the outdoor environment to the built environment (BE) has reduced our exposure to microbial diversity. The relative importance of factors that contribute to the composition of human-dominated BE microbial communities remains largely unknown. In their article in this issue, Chase and colleagues (J. Chase, J. Fouquier, M. Zare, D. L. Sonderegger, R. Knight, S. T. Kelley, J. Siegel, and J. G. Caporaso, mSystems 1(2):e00022-16, 2016, http://dx.doi.org/10.1128/mSystems.00022-16) present an office building study in which they controlled for environmental factors, geography, surface material, sampling location, and human interaction type. They found that surface location and geography were the strongest factors contributing to microbial community structure, while surface material had little effect. Even in the absence of direct human interaction, BE surfaces were composed of 25 to 30% human skin-associated taxa. The authors demonstrate how technical variation across sequencing runs is a major issue, especially in BE work, where the biomass is often low and the potential for PCR contaminants is high. Overall, the authors conclude that BE surfaces are desert-like environments where microbes passively accumulate. PMID:27832216

Global Change and the Earth System

NASA Astrophysics Data System (ADS)

Pollack, Henry N.

2004-08-01

The Earth system in recent years has come to mean the complex interactions of the atmosphere, biosphere, lithosphere and hydrosphere, through an intricate network of feedback loops. This system has operated over geologic time, driven principally by processes with long time scales. Over the lifetime of the solar system, the Sun has slowly become more radiant, and the geography of continents and oceans basins has evolved via plate tectonics. This geography has placed a first-order constraint on the circulation of ocean waters, and thus has strongly influenced regional and global climate. At shorter time scales, the Earth system has been influenced by Milankovitch orbital factors and occasional exogenous events such as bolide impacts. Under these influences the system chugged along for eons, until some few hundred thousand years ago, when one remarkable species evolved: Homo sapiens. As individuals, humans are of course insignificant in shaping the Earth system, but collectively the six billion human occupants of the planet now rival ``natural'' processes in modifying the Earth system. This profound human influence underlies the dubbing of the present epoch of geologic history as the ``Anthropocene.''

Empathy as an Aim for Curriculum: Lessons from History.

ERIC Educational Resources Information Center

Portal, Christopher

1983-01-01

Providing for imaginative, aesthetic, and intuitive aspects in the curriculum is a concern not limited to arts subjects. In fact the most fruitful attempts to integrate personal values and empathy occur in humanities subjects, such as history and geography. (IS)

Mutations at the S1 sites of methionine aminopeptidases from Escherichia coli and Homo sapiens reveal the residues critical for substrate specificity.

PubMed

Li, Jing-Ya; Cui, Yong-Mei; Chen, Ling-Ling; Gu, Min; Li, Jia; Nan, Fa-Jun; Ye, Qi-Zhuang

2004-05-14

Methionine aminopeptidase (MetAP) catalyzes the removal of methionine from newly synthesized polypeptides. MetAP carries out this cleavage with high precision, and Met is the only natural amino acid residue at the N terminus that is accepted, although type I and type II MetAPs use two different sets of residues to form the hydrophobic S1 site. Characteristics of the S1 binding pocket in type I MetAP were investigated by systematic mutation of each of the seven S1 residues in Escherichia coli MetAP type I (EcMetAP1) and human MetAP type I (HsMetAP1). We found that Tyr-65 and Trp-221 in EcMetAP1, as well as the corresponding residues Phe-197 and Trp-352 in HsMetAP1, were essential for the hydrolysis of a thiopeptolide substrate, Met-S-Gly-Phe. Mutation of Phe-191 to Ala in HsMetAP1 caused inactivity in contrast to the full activity of EcMetAP1(Y62A), which may suggest a subtle difference between the two type I enzymes. The more striking finding is that mutation of Cys-70 in EcMetAP1 or Cys-202 in HsMetAP1 opens up the S1 pocket. The thiopeptolides Leu-S-Gly-Phe and Phe-S-Gly-Phe, with previously unacceptable Leu or Phe as the N-terminal residue, became efficient substrates of EcMetAP1(C70A) and HsMetAP1(C202A). The relaxed specificity shown in these S1 site mutants for the N-terminal residues was confirmed by hydrolysis of peptide substrates and inhibition by reaction products. The structural features at the enzyme active site will be useful information for designing specific MetAP inhibitors for therapeutic applications.

Structural and functional attributes of malaria parasite diadenosine tetraphosphate hydrolase.

PubMed

Sharma, Arvind; Yogavel, Manickam; Sharma, Amit

2016-02-01

Malaria symptoms are driven by periodic multiplication cycles of Plasmodium parasites in human red blood corpuscles (RBCs). Malaria infection still accounts for ~600,000 annual deaths, and hence discovery of both new drug targets and drugs remains vital. In the present study, we have investigated the malaria parasite enzyme diadenosine tetraphosphate (Ap4A) hydrolase that regulates levels of signalling molecules like Ap4A by hydrolyzing them to ATP and AMP. We have tracked the spatial distribution of parasitic Ap4A hydrolase in infected RBCs, and reveal its unusual localization on the infected RBC membrane in subpopulation of infected cells. Interestingly, enzyme activity assays reveal an interaction between Ap4A hydrolase and the parasite growth inhibitor suramin. We also present a high resolution crystal structure of Ap4A hydrolase in apo- and sulphate- bound state, where the sulphate resides in the enzyme active site by mimicking the phosphate of substrates like Ap4A. The unexpected infected erythrocyte localization of the parasitic Ap4A hydrolase hints at a possible role of this enzyme in purinerigic signaling. In addition, atomic structure of Ap4A hydrolase provides insights for selective drug targeting.

Defects in the cappuccino (cno) gene on mouse chromosome 5 and human 4p cause Hermansky-Pudlak syndrome by an AP-3-independent mechanism.

PubMed

Gwynn, B; Ciciotte, S L; Hunter, S J; Washburn, L L; Smith, R S; Andersen, S G; Swank, R T; Dell'Angelica, E C; Bonifacino, J S; Eicher, E M; Peters, L L

2000-12-15

Defects in a triad of organelles (melanosomes, platelet granules, and lysosomes) result in albinism, prolonged bleeding, and lysosome abnormalities in Hermansky-Pudlak syndrome (HPS). Defects in HPS1, a protein of unknown function, and in components of the AP-3 complex cause some, but not all, cases of HPS in humans. There have been 15 inherited models of HPS described in the mouse, underscoring its marked genetic heterogeneity. Here we characterize a new spontaneous mutation in the mouse, cappuccino (cno), that maps to mouse chromosome 5 in a region conserved with human 4p15-p16. Melanosomes of cno/cno mice are immature and dramatically decreased in number in the eye and skin, resulting in severe oculocutaneous albinism. Platelet dense body contents (adenosine triphosphate, serotonin) are markedly deficient, leading to defective aggregation and prolonged bleeding. Lysosomal enzyme concentrations are significantly elevated in the kidney and liver. Genetic, immunofluorescence microscopy, and lysosomal protein trafficking studies indicate that the AP-3 complex is intact in cno/cno mice. It was concluded that the cappuccino gene encodes a product involved in an AP-3-independent mechanism critical to the biogenesis of lysosome-related organelles. (Blood. 2000;96:4227-4235)

On the Perceptual Subprocess of Absolute Pitch.

PubMed

Kim, Seung-Goo; Knösche, Thomas R

2017-01-01

Absolute pitch (AP) is the rare ability of musicians to identify the pitch of tonal sound without external reference. While there have been behavioral and neuroimaging studies on the characteristics of AP, how the AP is implemented in human brains remains largely unknown. AP can be viewed as comprising of two subprocesses: perceptual (processing auditory input to extract a pitch chroma) and associative (linking an auditory representation of pitch chroma with a verbal/non-verbal label). In this review, we focus on the nature of the perceptual subprocess of AP. Two different models on how the perceptual subprocess works have been proposed: either via absolute pitch categorization (APC) or based on absolute pitch memory (APM). A major distinction between the two views is that whether the AP uses unique auditory processing (i.e., APC) that exists only in musicians with AP or it is rooted in a common phenomenon (i.e., APM), only with heightened efficiency. We review relevant behavioral and neuroimaging evidence that supports each notion. Lastly, we list open questions and potential ideas to address them.

On the Perceptual Subprocess of Absolute Pitch

PubMed Central

Kim, Seung-Goo; Knösche, Thomas R.

2017-01-01

Absolute pitch (AP) is the rare ability of musicians to identify the pitch of tonal sound without external reference. While there have been behavioral and neuroimaging studies on the characteristics of AP, how the AP is implemented in human brains remains largely unknown. AP can be viewed as comprising of two subprocesses: perceptual (processing auditory input to extract a pitch chroma) and associative (linking an auditory representation of pitch chroma with a verbal/non-verbal label). In this review, we focus on the nature of the perceptual subprocess of AP. Two different models on how the perceptual subprocess works have been proposed: either via absolute pitch categorization (APC) or based on absolute pitch memory (APM). A major distinction between the two views is that whether the AP uses unique auditory processing (i.e., APC) that exists only in musicians with AP or it is rooted in a common phenomenon (i.e., APM), only with heightened efficiency. We review relevant behavioral and neuroimaging evidence that supports each notion. Lastly, we list open questions and potential ideas to address them. PMID:29085275

Sketching for Developing Critical Thinking Skills

NASA Astrophysics Data System (ADS)

Eriksson, S. C.; Wang, P.; Sim, T. B.; Goh, E.; Ng, H. K.

2013-12-01

Sketching is a valuable field technique to support a person's observation, recording, interpretation and communication of important features in both natural and human-made landscapes. The Singapore geography syllabus employs an inquiry approach and encourages sketching as a fundamental geographical skill. Sketching allows the learner to connect with the world through a personal and kinesthetic experience. The Earth Observatory of Singapore collaborates with the Singapore Geography Teachers' Association, Urban Sketchers, and National Institute of Education professional development to give teachers both basic sketching skills and the opportunity to develop those skills in a scaffolded environment. In Singapore, geography and geology skills overlap in content area of coastal processes, climate change, and plate tectonics with its associated natural hazards such as volcanoes, earthquakes, and tsunami. Both disciplines are interested in how people live on the Earth. Likewise, basic skills such as observing, classifying, measuring, and communicating cut across disciplines of social and natural sciences in order to analyze, synthesize, and evaluate information about the world. Hence, sketching, commonly considered an art skill, is used to further scientific thinking. This somewhat unique collaboration to develop sketching in teachers is based on the long tradition of sketches in geological field work, the newly popular urban sketching community, and professional development by a professional organization and the Singapore National Institute of Education. Workshops provide technique as well as opportunities for sketching with experts in different areas relevant to the geography curriculum.

Monolithic silica spin column extraction and simultaneous derivatization of amphetamines and 3,4-methylenedioxyamphetamines in human urine for gas chromatographic-mass spectrometric detection.

PubMed

Nakamoto, Akihiro; Nishida, Manami; Saito, Takeshi; Kishiyama, Izumi; Miyazaki, Shota; Murakami, Katsunori; Nagao, Masataka; Namura, Akira

2010-02-19

A simple, sensitive, and specific method with gas chromatography-mass spectrometry was developed for simultaneous extraction and derivatization of amphetamines (APs) and 3,4-methylenedioxyamphetamines (MDAs) in human urine by using a monolithic silica spin column. All the procedures, such as sample loading, washing, and elution were performed by centrifugation. APs and MDAs in urine were adsorbed on the monolithic silica and derivatized with propyl chloroformate in the column. Methamphetamine-d(5) was used as an internal standard. The linear ranges were 0.01-5.0 microg mL(-1) for methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) and 0.02-5.0 microg mL(-1) for amphetamine (AP) and 3,4-methylenedioxyamphetamine (MDA) (coefficient of correlation > or = 0.995). The recovery of APs and MDAs in urine was 84-94%, and the relative standard deviation of the intra- and interday reproducibility for urine samples containing 0.1, 1.0, and 4.0 microg mL(-1) of APs and MDAs ranged from 1.4% to 13.6%. The lowest detection limit (signal-to-noise ratio > or = 3) in urine was 5 ng mL(-1) for MA and MDMA and 10 ng mL(-1) for AP and MDA. The proposed method can be used to perform simultaneous extraction and derivatization on spin columns that have been loaded with a small quantity of solvent by using centrifugation. Copyright 2009 Elsevier B.V. All rights reserved.

Defective pigment granule biogenesis and aberrant behavior caused by mutations in the Drosophila AP-3beta adaptin gene ruby.

PubMed Central

Kretzschmar, D; Poeck, B; Roth, H; Ernst, R; Keller, A; Porsch, M; Strauss, R; Pflugfelder, G O

2000-01-01

Lysosomal protein trafficking is a fundamental process conserved from yeast to humans. This conservation extends to lysosome-like organelles such as mammalian melanosomes and insect eye pigment granules. Recently, eye and coat color mutations in mouse (mocha and pearl) and Drosophila (garnet and carmine) were shown to affect subunits of the heterotetrameric adaptor protein complex AP-3 involved in vesicle trafficking. Here we demonstrate that the Drosophila eye color mutant ruby is defective in the AP-3beta subunit gene. ruby expression was found in retinal pigment and photoreceptor cells and in the developing central nervous system. ruby mutations lead to a decreased number and altered size of pigment granules in various cell types in and adjacent to the retina. Humans with lesions in the related AP-3betaA gene suffer from Hermansky-Pudlak syndrome, which is caused by defects in a number of lysosome-related organelles. Hermansky-Pudlak patients have a reduced skin pigmentation and suffer from internal bleeding, pulmonary fibrosis, and visual system malfunction. The Drosophila AP-3beta adaptin also appears to be involved in processes other than eye pigment granule biogenesis because all ruby allele combinations tested exhibited defective behavior in a visual fixation paradigm. PMID:10790396

Correlation of bistranded clustered abasic DNA lesion processing with structural and dynamic DNA helix distortion

PubMed Central

Bignon, Emmanuelle; Gattuso, Hugo; Morell, Christophe; Dehez, François; Georgakilas, Alexandros G.; Monari, Antonio; Dumont, Elise

2016-01-01

Clustered apurinic/apyrimidinic (AP; abasic) DNA lesions produced by ionizing radiation are by far more cytotoxic than isolated AP lesion entities. The structure and dynamics of a series of seven 23-bp oligonucleotides featuring simple bistranded clustered damage sites, comprising of two AP sites, zero, one, three or five bases 3′ or 5′ apart from each other, were investigated through 400 ns explicit solvent molecular dynamics simulations. They provide representative structures of synthetically engineered multiply damage sites-containing oligonucleotides whose repair was investigated experimentally (Nucl. Acids Res. 2004, 32:5609-5620; Nucl. Acids Res. 2002, 30: 2800–2808). The inspection of extrahelical positioning of the AP sites, bulge and non Watson–Crick hydrogen bonding corroborates the experimental measurements of repair efficiencies by bacterial or human AP endonucleases Nfo and APE1, respectively. This study provides unprecedented knowledge into the structure and dynamics of clustered abasic DNA lesions, notably rationalizing the non-symmetry with respect to 3′ to 5′ position. In addition, it provides strong mechanistic insights and basis for future studies on the effects of clustered DNA damage on the recognition and processing of these lesions by bacterial or human DNA repair enzymes specialized in the processing of such lesions. PMID:27587587

CLIMATE IMPACTS ON REGIONAL WATER

EPA Science Inventory

The New England region (including the 6 New England
states plus upstate New York) offers a very diverse geography,
matched by an equally diverse economy and human
population. Livelihoods throughout the region are based
on service industries that depend heavily on comm...

Geography: Key to World Understanding.

ERIC Educational Resources Information Center

Dando, William A.

1990-01-01

Delineates the nature of applied geography, asserting that geography links the natural and social sciences. Underscores geography's role in data analysis and problem solving on a global scale. Traces the discipline's history. Maps geography's status in higher education institutions. Discusses new technologies used by geographers. Summarizes career…

Tumour necrosis factor-α regulates human eosinophil apoptosis via ligation of TNF-receptor 1 and balance between NF-κB and AP-1.

PubMed

Kankaanranta, Hannu; Ilmarinen, Pinja; Zhang, Xianzhi; Adcock, Ian M; Lahti, Aleksi; Barnes, Peter J; Giembycz, Mark A; Lindsay, Mark A; Moilanen, Eeva

2014-01-01

Eosinophils play a central role in asthma. The present study was performed to investigate the effect of tumour necrosis factor-α (TNF-α) on longevity of isolated human eosinophils. In contrast to Fas, TNF-α inhibited eosinophil apoptosis as evidenced by a combination of flow cytometry, DNA fragmentation assay and morphological analyses. The effect of TNF-α on eosinophil apoptosis was reversed by a TNF-α neutralising antibody. The anti-apoptotic effect of TNF-α was not due to autocrine release of known survival-prolonging cytokines interleukins 3 and 5 or granulocyte-macrophage-colony-stimulating factor as their neutralisation did not affect the effect of TNF-α. The anti-apoptotic signal was mediated mainly by the TNF-receptor 1. TNF-α induced phosphorylation and degradation of IκB and an increase in NF-κB DNA-binding activity. The survival-prolonging effect of TNF-α was reversed by inhibitors of NF-κB pyrrolidinedithiocarbamate and gliotoxin and by an inhibitor of IκB kinase, BMS-345541. TNF-α induced also an increase in AP-1 DNA-binding activity and the antiapoptotic effect of TNF-α was potentiated by inhibitors of AP-1, SR 11302 and tanshinone IIA and by an inhibitor of c-jun-N-terminal kinase, SP600125, which is an upstream kinase activating AP-1. Our results thus suggest that TNF-α delays human eosinophil apoptosis via TNF-receptor 1 and the resulting changes in longevity depend on yin-yang balance between activation of NF-κB and AP-1.

THE AP-2 CLATHRIN ADAPTOR MEDIATES ENDOCYTOSIS OF AN INHIBITORY KILLER CELL Ig-LIKE RECEPTOR (KIR) IN HUMAN NK CELLS1

PubMed Central

Purdy, Amanda K.; Alvarez-Arias, Diana A.; Oshinsky, Jennifer; James, Ashley M.; Serebriiskii, Ilya; Campbell, Kerry S.

2014-01-01

Stable surface expression of human inhibitory killer cell immunoglobulin-like receptors (KIR) is critical for controlling NK cell function and maintaining NK cell tolerance toward normal MHC-I+ cells. Our recent experiments, however, have found that antibody-bound KIR3DL1 (3DL1) readily leaves the cell surface and undergoes endocytosis to early/recycling endosomes and subsequently to late endosomes. We found that 3DL1 internalization is at least partially mediated by an interaction between the μ2 subunit of the AP-2 clathrin adaptor complex and ITIM tyrosine residues in the cytoplasmic domain of 3DL1. Disruption of the 3DL1/μ2 interaction, either by mutation of the ITIM tyrosines in 3DL1 or mutation of μ2, significantly diminished endocytosis and increased surface expression of 3DL1 in human primary NK cells and cell lines. Furthermore, we found that the 3DL1/AP-2 interaction is diminished upon antibody engagement with the receptor, as compared to untreated cells. Thus, we have identified AP-2-mediated endocytosis as a mechanism regulating the surface levels of inhibitory KIR though their ITIM domains. Based upon our results, we propose a model in which non-engaged KIR are internalized by this mechanism, whereas engagement with MHC-I ligand would diminish AP-2 binding, thereby prolonging stable receptor surface expression and promoting inhibitory function. Furthermore, this ITIM-mediated mechanism may similarly regulate the surface expression of other inhibitory immune receptors. PMID:25238755

Synthesis, characterization and biological evaluation of novel chalcone sulfonamide hybrids as potent intestinal alkaline phosphatase inhibitors.

PubMed

Ejaz, Syeda Abida; Saeed, Aamer; Siddique, Muhammad Nasir; Nisa, Zaib Un; Khan, Samiullah; Lecka, Joanna; Sévigny, Jean; Iqbal, Jamshed

2017-02-01

Alkaline phosphatase (AP) and ecto-5'-nucleotidase (e5'NT) belong to same family that hydrolyze the extracellular nucleotides and ensure the bioavailability of nucleotides and nucleosides at purinergic receptors. During pathophysiological conditions, the over expression of AP and e5'NT lead to an increased production of adenosine that enhance tumor proliferation, invasiveness, neoangiogenesis and disrupts the body antitumor response. As both enzymes are abundantly expressed in above mentioned conditions, therefore it is of great interest to synthesize and develop potent inhibitors of these enzymes that augment the antitumor therapy. Herein we reported the synthesis and biological activity of a new series of chalcone-sulfonamide hybrids (4a-j). These derivatives were then evaluated for their inhibitory potential against two members of ecto-nucleotidase family, e5'NT (human and rat) and APs isozyme (intestinal and tissue nonspecific). Only six derivatives were found to inhibit both human and rat e5'NT enzymes. Compounds 4e and 4d showed maximum inhibition of human and rat e5'NT with an IC 50 ±SEM=0.26±0.01 and 0.33±0.004μM, respectively. Moreover, on APs, these derivatives were identified as the selective inhibitors of calf intestinal AP (c-IAP). The derivative 4a exhibited maximum inhibition of c-IAP with an IC 50 ±SEM=0.12±0.02μM. In conclusion, these chalcone-sulfonamide hybrids exhibited dual inhibition of both family of isozymes but was more selective towards c-IAP enzyme. Copyright © 2017 Elsevier Inc. All rights reserved.

In vitro and in vivo antioxidant potential of milks, yoghurts, fermented milks and cheeses: a narrative review of evidence.

PubMed

Fardet, Anthony; Rock, Edmond

2018-06-01

The antioxidant potential (AP) is an important nutritional property of foods, as increased oxidative stress is involved in most diet-related chronic diseases. In dairy products, the protein fraction contains antioxidant activity, especially casein. Other antioxidants include: antioxidant enzymes; lactoferrin; conjugated linoleic acid; coenzyme Q10; vitamins C, E, A and D3; equol; uric acid; carotenoids; and mineral activators of antioxidant enzymes. The AP of dairy products has been extensively studied in vitro, with few studies in animals and human subjects. Available in vivo studies greatly differ in their design and objectives. Overall, on a 100 g fresh weight-basis, AP of dairy products is close to that of grain-based foods and vegetable or fruit juices. Among dairy products, cheeses present the highest AP due to their higher protein content. AP of milk increases during digestion by up to 2·5 times because of released antioxidant peptides. AP of casein is linked to specific amino acids, whereas β-lactoglobulin thiol groups play a major role in the AP of whey. Thermal treatments such as ultra-high temperature processing have no clear effect on the AP of milk. Raw fat-rich milks have higher AP than less fat-rich milk, because of lipophilic antioxidants. Probiotic yoghurts and fermented milks have higher AP than conventional yoghurt and milk because proteolysis by probiotics releases antioxidant peptides. Among the probiotics, Lactobacillus casei/acidophilus leads to the highest AP. The data are insufficient for cheese, but fermentation-based changes appear to make a positive impact on AP. In conclusion, AP might participate in the reported dairy product-protective effects against some chronic diseases.

Geography in Education.

ERIC Educational Resources Information Center

Graves, Norman J.

The book reviews the historical development of geography as discipline and discusses the current status of geography teaching in British schools. Chapter one briefly identifies the rationale for including geography in the educational curriculum. Chapter two traces the role of geography in academic study from ancient Greece to the present. Growth…

Geography Teachers' Stories of Sustainability: An Introduction to Narrative Research

ERIC Educational Resources Information Center

Brooks, Clare

2016-01-01

Geography teacher recruitment and retention is an important issue for the future of geography education. This Special Issue of "International Research in Geographical and Environmental Education" ("IRGEE") tackles this issue head on by focusing on geography teachers' narratives about their experiences of teaching geography, and…

The Four Traditions of Geography: A Unified Future Ahead?

ERIC Educational Resources Information Center

Marran, James F.

1985-01-01

Identifies William Pattison's four traditions of geography (spatial dimension, area studies, people-environment interaction, and earth science); discusses how geography instruction at secondary level has been one dimensional; describes High School Geography Project's efforts to revise geography curriculum by unifying Pattison's traditions (1960s);…

Geographical education in Russia: state-of-the-art and new perspectives

NASA Astrophysics Data System (ADS)

Chalov, Sergey R.

2010-05-01

Up-today education systems of different countries face new perspectives in globalizing World. The Russian higher education framework was basically incompatible with the process of making academic degree standards and quality assurance standards more comparable throughout the World (so called Bologna process for Europe). So did Earth Sciences education framework. Today the key question in the further development of Earth sciences in Russia is the interaction with European education system. At the crossroads it is challenging to analyze the history and state-of-the-art. We considered the question on the example of one of the largest centers of the Earth Sciences education in Russia - Faculty of Geography of Lomonosov Moscow State University, which is moreover regarded to be one of the largest scientific and educational centers of geography in the World. There are 1200 students and 180 PhD students studying on the Faculty. The Faculty consists of 15 departments, 8 research laboratories and 4 field stations, where 850 employees work. Tuition of geography was established at Lomonosov Moscow State University since the day of its foundation. The significance of geographical studies at the University, which originally comprised the Faculty of Philosophy, the Faculty of Law and the Faculty of Medicine, was already mentioned in the draft plan of its establishment (1755), which said that «anyone wishing to attend professors' lectures at the University has to learn foreign languages and first scientific basis beforehand". For this purpose two «gymnasiums» consisting of four schools were es-tablished at the University. Geography was included into the curriculum of the «first scientific basis school» and the «school of the distinguished European languages» - German and French. Today Geography in Russia is regarded to be one of the base sciences that are devoted to the problem of society and environment and their interactions. Geography was gone far from the descriptive field of science and in recent years combined key aspects of Earth Sciences. A new structure of geographical science and education has developed under the influence of modern trends in Geosciences. There are fifteen specialized departments on the Faculty of Geography of Lomonosov Moscow State University. The structure of the Faculty of Geography comprises 3 main profiles: the Environmental Geography, Human Geography and Hydrometeorology. Research and education of the Faculty of Geography of Lomonosov Moscow State University is fundamental and application-oriented in nature. To find solutions for society's present and future demands is the main task of the research and education which is trend to become research-oriented. Eight multidisciplinary primary research laboratories contribute to the research-oriented education. Modern global processes and terms such as sustainability, assessing risk and reducing disaster in environmental hazards, global and regional changes of environment and climate posed new perspectives in the geographical education. Integrative trends were in progress and that could be characterized by the following: - Development of new integrative branch of geography (so called "geoecology") as a response to increasing anthropogenic impact on environment; - Development of supplementary education (GIS, habitation ecology, landscape design etc); - Interdisciplinary features of such branches as environmental impact assessment and audit; - Scientific basis of sustainable development and nature management. Both with organizational issues (i.e. perfection of student practices, field studies and modernization of field stations; creation of training courses for foreign students; strengthening special training programmes in schools and development of distance learning) this integrative trends determine further development of the Geographical education in Russia. All of them greatly depend on the integration processes between Russia and Europe. Firm place of the Geography in the European Earth Sciences system provides both demand for the society and key role in future of science.

Another Strategy for Teaching Histology to A&P Students: Classification versus Memorization.

ERIC Educational Resources Information Center

Bavis, Ryan W.; Seveyka, Jerred; Shigeoka, Cassie A.

2000-01-01

Defines dichotomous keys as common learning tools based on identification rather than memorization. Provides an example of a dichotomous key developed for introducing histology in human anatomy and physiology (A&P) courses and explains how students can use the dichotomous key. Discusses the goals of the exercises and the process of…

Structure and substrate-binding mechanism of human Ap4A hydrolase.

PubMed

Swarbrick, James D; Buyya, Smrithi; Gunawardana, Dilantha; Gayler, Kenwyn R; McLennan, Alexander G; Gooley, Paul R

2005-03-04

Asymmetric diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) hydrolases play a major role in maintaining homeostasis by cleaving the metabolite diadenosine tetraphosphate (Ap(4)A) back into ATP and AMP. The NMR solution structures of the 17-kDa human asymmetric Ap(4)A hydrolase have been solved in both the presence and absence of the product ATP. The adenine moiety of the nucleotide predominantly binds in a ring stacking arrangement equivalent to that observed in the x-ray structure of the homologue from Caenorhabditis elegans. The binding site is, however, markedly divergent to that observed in the plant/pathogenic bacteria class of enzymes, opening avenues for the exploration of specific therapeutics. Binding of ATP induces substantial conformational and dynamic changes that were not observed in the C. elegans structure. In contrast to the C. elegans homologue, important side chains that play a major role in substrate binding do not have to reorient to accommodate the ligand. This may have important implications in the mechanism of substrate recognition in this class of enzymes.

NOTCH3 is expressed in human apical papilla and in subpopulations of stem cells isolated from the tissue.

PubMed

Jamal, Mohamed; Chogle, Sami M; Karam, Sherif M; Huang, George T-J

2015-09-01

NOTCH plays a role in regulating stem cell function and fate decision. It is involved in tooth development and injury repair. Information regarding NOTCH expression in human dental root apical papilla (AP) and its residing stem cells (SCAP) is limited. Here we investigated the expression of NOTCH3, its ligand JAG1, and mesenchymal stem cell markers CD146 and STRO-1 in the AP or in the primary cultures of SCAP isolated from AP. Our in situ immunostaining showed that in the AP NOTCH3 and CD146 were co-expressed and associated with blood vessels having NOTCH3 located more peripherally. In cultured SCAP, NOTCH3 and JAG1 were co-expressed. Flow cytometry analysis showed that 7%, 16% and 98% of the isolated SCAP were positive for NOTCH3, STRO-1 and CD146, respectively with a rare 1.5% subpopulation of SCAP co-expressing all three markers. The expression level of NOTCH3 reduced when SCAP underwent osteogenic differentiation. Our findings are the first step towards defining the regulatory role of NOTCH3 in SCAP fate decision.

Characterization of a Y-Family DNA Polymerase eta from the Eukaryotic Thermophile Alvinella pompejana

PubMed Central

Kashiwagi, Sayo; Kuraoka, Isao; Fujiwara, Yoshie; Hitomi, Kenichi; Cheng, Quen J.; Fuss, Jill O.; Shin, David S.; Masutani, Chikahide; Tainer, John A.; Hanaoka, Fumio; Iwai, Shigenori

2010-01-01

Human DNA polymerase η (HsPolη) plays an important role in translesion synthesis (TLS), which allows for replication past DNA damage such as UV-induced cis-syn cyclobutane pyrimidine dimers (CPDs). Here, we characterized ApPolη from the thermophilic worm Alvinella pompejana, which inhabits deep-sea hydrothermal vent chimneys. ApPolη shares sequence homology with HsPolη and contains domains for binding ubiquitin and proliferating cell nuclear antigen. Sun-induced UV does not penetrate Alvinella's environment; however, this novel DNA polymerase catalyzed efficient and accurate TLS past CPD, as well as 7,8-dihydro-8-oxoguanine and isomers of thymine glycol induced by reactive oxygen species. In addition, we found that ApPolη is more thermostable than HsPolη, as expected from its habitat temperature. Moreover, the activity of this enzyme was retained in the presence of a higher concentration of organic solvents. Therefore, ApPolη provides a robust, human-like Polη that is more active after exposure to high temperatures and organic solvents. PMID:20936172

Celebrating Geography: Geography in Everyday Life.

ERIC Educational Resources Information Center

Fitzhugh, William P.

The paper suggests that the five fundamental themes of geography can serve as a good starting point for understanding how geography affects lives everyday in every way. Geography serves to remind people how interwoven geographic concepts are in individuals' lives. Ten activities are suggested to incorporate the five fundamental themes into a…

A Road Map for Improving Geography Assessment

ERIC Educational Resources Information Center

Wertheim, Jill A.; Edelson, Daniel C.; Hildebrant, Barbara; Hinde, Elizabeth; Kenney, Marianne; Kolvoord, Robert; Lanegran, David; Marcello, Jody Smothers; Morrill, Robert; Ruiz-Primo, Maria; Seixas, Peter; Shavelson, Richard

2013-01-01

In late 2012, both the second edition of the "Geography for Life: National Geography Standards" and the National Science Foundation-funded "Road Map for Geography Education Project" reports were released; the former document describes the conceptual goals for K-12 geography education, and the latter, a route to coordinating reform efforts to…

A Content Comparison of Six Physical Geography Textbooks Spanning a Century

ERIC Educational Resources Information Center

Jennings, Steven A.

2006-01-01

Six physical geography textbooks published between 1901 and 2002 were qualitatively analysed for content and compared to the National Geography Standards. General relationships to dominant approaches to geography, content, and pedagogy of these textbooks were analysed. These textbooks reflect dominant approaches to geography at the time they were…

Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53

PubMed Central

Martinez-Zapien, Denise; Ruiz, Francesc Xavier; Poirson, Juline; Mitschler, André; Ramirez-Ramos, Juan; Forster, Anne; Cousido-Siah, Alexandra; Masson, Murielle; Pol, Scott Vande; Podjarny, Alberto; Travé, Gilles; Zanier, Katia

2015-01-01

Summary The p53 pro-apoptotic tumor suppressor is mutated or functionally altered in most cancers. In epithelial tumors induced by “high-risk” mucosal Human Papillomaviruses (hrm-HPVs), including human cervical carcinoma and a growing number of head-and-neck cancers 1, p53 is degraded by the viral oncoprotein E6 2. In this process, E6 binds to a short LxxLL consensus sequence within the cellular ubiquitin ligase E6AP 3. Subsequently, the E6/E6AP heterodimer recruits and degrades p53 4. Neither E6 nor E6AP are separately able to recruit p53 3,5, and the precise mode of assembly of E6, E6AP and p53 is unknown. Here, we solved the crystal structure of a ternary complex comprising full-length HPV16 E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumor suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against HPV-mediated oncogenesis. PMID:26789255

AP2 adaptor complex mediates bile salt export pump internalization and modulates its hepatocanalicular expression and transport function.

PubMed

Hayashi, Hisamitsu; Inamura, Kaori; Aida, Kensuke; Naoi, Sotaro; Horikawa, Reiko; Nagasaka, Hironori; Takatani, Tomozumi; Fukushima, Tamio; Hattori, Asami; Yabuki, Takashi; Horii, Ikuo; Sugiyama, Yuichi

2012-06-01

The bile salt export pump (BSEP) mediates the biliary excretion of bile salts and its dysfunction induces intrahepatic cholestasis. Reduced canalicular expression of BSEP resulting from the promotion of its internalization is one of the causes of this disease state. However, the molecular mechanism underlying BSEP internalization from the canalicular membrane (CM) remains unknown. We have shown previously that 4-phenylbutyrate (4PBA), a drug used for ornithine transcarbamylase deficiency (OTCD), inhibited internalization and subsequent degradation of cell-surface-resident BSEP. The current study found that 4PBA treatment decreased significantly the expression of α- and μ2-adaptin, both of which are subunits of the AP2 adaptor complex (AP2) that mediates clathrin-dependent endocytosis, in liver specimens from rats and patients with OTCD, and that BSEP has potential AP2 recognition motifs in its cytosolic region. Based on this, the role of AP2 in BSEP internalization was explored further. In vitro analysis with 3×FLAG-human BSEP-expressing HeLa cells and human sandwich-culture hepatocytes indicates that the impairment of AP2 function by RNA interference targeting of α-adaptin inhibits BSEP internalization from the plasma membrane and increases its cell-surface expression and transport function. Studies using immunostaining, coimmunoprecipitation, glutathione S-transferase pulldown assay, and time-lapse imaging show that AP2 interacts with BSEP at the CM through a tyrosine motif at the carboxyl terminus of BSEP and mediates BSEP internalization from the CM of hepatocytes. AP2 mediates the internalization and subsequent degradation of CM-resident BSEP through direct interaction with BSEP and thereby modulates the canalicular expression and transport function of BSEP. This information should be useful for understanding the pathogenesis of severe liver diseases associated with intrahepatic cholestasis. Copyright © 2012 American Association for the Study of Liver Diseases.

Traditional Chinese medicine Astragalus polysaccharide enhanced antitumor effects of the angiogenesis inhibitor apatinib in pancreatic cancer cells on proliferation, invasiveness, and apoptosis

PubMed Central

Wu, Jun; Wang, Jing; Su, Qiang; Ding, Wei; Li, Teng; Yu, Junxian; Cao, Bangwei

2018-01-01

Background Traditional chemotherapy and molecular targeted therapy have shown modest effects on the survival of patients with pancreatic cancer. The current study aimed to investigate the antitumor effects of apatinib, Astragalus polysaccharide (APS), and the combination of both the drugs in pancreatic cancer cells and further explore the molecular mechanisms in vitro. Materials and methods Expression of vascular endothelial growth factor receptor-2 (VEGFR-2) in human pancreatic cancer cell lines ASPC-1, PANC-1, and SW1990 was detected by Western blotting. Cell proliferation was measured by MTS, and migration and invasion were detected by wound-healing and Transwell assays, respectively. Cell apoptosis rate was determined by flow cytometry and cellular autophagy level affected by apatinib, and APS was analyzed by Western blotting. Results Human pancreatic cancer cell lines ASPC-1 and PANC-1 expressed VEGFR-2, but VEGFR-2 was not detected in SW1990. Either apatinib or APS inhibited cell proliferation in a dose-dependent manner in ASPC-1 and PANC-1. APS in combination with apatinib showed enhanced inhibitory effects on cell migration and invasion compared with apatinib monotherapy in ASPC-1 and PANC-1. Meanwhile, APS combined with apatinib strongly increased cell apoptosis percentage. Western blotting showed that the combination of APS and apatinib significantly enhanced the downregulation of phosphorylated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) (p-AKT and p-ERK) as well as matrix metalloproteinases-9 (MMP-9) expression. In addition, both apatinib and APS induced cellular autophagy. However, the expression of autophagy-related proteins was not further elevated in the combination group. Conclusion The study first demonstrated that apatinib showed potentially inhibitory effects in pancreatic cancer cells and that APS enhanced the antitumor effects of apatinib through further downregulating the expression of phosphorylation of AKT and ERK as well as MMP-9. PMID:29785118

Traditional Chinese medicine Astragalus polysaccharide enhanced antitumor effects of the angiogenesis inhibitor apatinib in pancreatic cancer cells on proliferation, invasiveness, and apoptosis.

PubMed

Wu, Jun; Wang, Jing; Su, Qiang; Ding, Wei; Li, Teng; Yu, Junxian; Cao, Bangwei

2018-01-01

Traditional chemotherapy and molecular targeted therapy have shown modest effects on the survival of patients with pancreatic cancer. The current study aimed to investigate the antitumor effects of apatinib, Astragalus polysaccharide (APS), and the combination of both the drugs in pancreatic cancer cells and further explore the molecular mechanisms in vitro. Expression of vascular endothelial growth factor receptor-2 (VEGFR-2) in human pancreatic cancer cell lines ASPC-1, PANC-1, and SW1990 was detected by Western blotting. Cell proliferation was measured by MTS, and migration and invasion were detected by wound-healing and Transwell assays, respectively. Cell apoptosis rate was determined by flow cytometry and cellular autophagy level affected by apatinib, and APS was analyzed by Western blotting. Human pancreatic cancer cell lines ASPC-1 and PANC-1 expressed VEGFR-2, but VEGFR-2 was not detected in SW1990. Either apatinib or APS inhibited cell proliferation in a dose-dependent manner in ASPC-1 and PANC-1. APS in combination with apatinib showed enhanced inhibitory effects on cell migration and invasion compared with apatinib monotherapy in ASPC-1 and PANC-1. Meanwhile, APS combined with apatinib strongly increased cell apoptosis percentage. Western blotting showed that the combination of APS and apatinib significantly enhanced the downregulation of phosphorylated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) (p-AKT and p-ERK) as well as matrix metalloproteinases-9 (MMP-9) expression. In addition, both apatinib and APS induced cellular autophagy. However, the expression of autophagy-related proteins was not further elevated in the combination group. The study first demonstrated that apatinib showed potentially inhibitory effects in pancreatic cancer cells and that APS enhanced the antitumor effects of apatinib through further downregulating the expression of phosphorylation of AKT and ERK as well as MMP-9.

Research on Schools, Neighborhoods and Communities: Toward Civic Responsibility

ERIC Educational Resources Information Center

Tate, William F., IV, Ed.

2012-01-01

"Research on Schools, Neighborhoods, and Communities: Toward Civic Responsibility" focuses on research and theoretical developments related to the role of geography in education, human development, and health. William F. Tate IV, the Edward Mallinckrodt Distinguished University Professor in Arts & Sciences at Washington University in…

Learning for Change in World Society: Reflections, Activities and Resources.

ERIC Educational Resources Information Center

One World Trust, London (England).

The resource booklet contains readings and activities for British secondary school world affairs classes. The material lends itself toward incorporation into various curricula, including history, geography, social studies, humanities, environmental studies, language and literature, home economics, math, and science. Subject matter focuses on…

1979 National Unified Entrance Examination for Institutions of Higher Education.

ERIC Educational Resources Information Center

Chinese Education, 1979

1979-01-01

The article presents translations of Chinese college entrance examinations in the fields of politics, Chinese language and literature, mathematics, humanities, physics, chemistry, history, geography, and English. Translations are also presented of the 1979 review syllabus for 1979 for the same subject areas. (DB)

Visualizing the Geography of the Diseases of China: Western Disease Maps from Analytical Tools to Tools of Empire, Sovereignty, and Public Health Propaganda, 1878-1929.

PubMed

Hanson, Marta

2017-09-01

Argument This article analyzes for the first time the earliest western maps of diseases in China spanning fifty years from the late 1870s to the end of the 1920s. The 24 featured disease maps present a visual history of the major transformations in modern medicine from medical geography to laboratory medicine wrought on Chinese soil. These medical transformations occurred within new political formations from the Qing dynasty (1644-1911) to colonialism in East Asia (Hong Kong, Taiwan, Manchuria, Korea) and hypercolonialism within China (Tianjin, Shanghai, Amoy) as well as the new Republican Chinese nation state (1912-49). As a subgenre of persuasive graphics, physicians marshaled disease maps for various rhetorical functions within these different political contexts. Disease maps in China changed from being mostly analytical tools to functioning as tools of empire, national sovereignty, and public health propaganda legitimating new medical concepts, public health interventions, and political structures governing over human and non-human populations.

Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity.

PubMed

Passini, Elisa; Britton, Oliver J; Lu, Hua Rong; Rohrbacher, Jutta; Hermans, An N; Gallacher, David J; Greig, Robert J H; Bueno-Orovio, Alfonso; Rodriguez, Blanca

2017-01-01

Early prediction of cardiotoxicity is critical for drug development. Current animal models raise ethical and translational questions, and have limited accuracy in clinical risk prediction. Human-based computer models constitute a fast, cheap and potentially effective alternative to experimental assays, also facilitating translation to human. Key challenges include consideration of inter-cellular variability in drug responses and integration of computational and experimental methods in safety pharmacology. Our aim is to evaluate the ability of in silico drug trials in populations of human action potential (AP) models to predict clinical risk of drug-induced arrhythmias based on ion channel information, and to compare simulation results against experimental assays commonly used for drug testing. A control population of 1,213 human ventricular AP models in agreement with experimental recordings was constructed. In silico drug trials were performed for 62 reference compounds at multiple concentrations, using pore-block drug models (IC 50 /Hill coefficient). Drug-induced changes in AP biomarkers were quantified, together with occurrence of repolarization/depolarization abnormalities. Simulation results were used to predict clinical risk based on reports of Torsade de Pointes arrhythmias, and further evaluated in a subset of compounds through comparison with electrocardiograms from rabbit wedge preparations and Ca 2+ -transient recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). Drug-induced changes in silico vary in magnitude depending on the specific ionic profile of each model in the population, thus allowing to identify cell sub-populations at higher risk of developing abnormal AP phenotypes. Models with low repolarization reserve (increased Ca 2+ /late Na + currents and Na + /Ca 2+ -exchanger, reduced Na + /K + -pump) are highly vulnerable to drug-induced repolarization abnormalities, while those with reduced inward current density (fast/late Na + and Ca 2+ currents) exhibit high susceptibility to depolarization abnormalities. Repolarization abnormalities in silico predict clinical risk for all compounds with 89% accuracy. Drug-induced changes in biomarkers are in overall agreement across different assays: in silico AP duration changes reflect the ones observed in rabbit QT interval and hiPS-CMs Ca 2+ -transient, and simulated upstroke velocity captures variations in rabbit QRS complex. Our results demonstrate that human in silico drug trials constitute a powerful methodology for prediction of clinical pro-arrhythmic cardiotoxicity, ready for integration in the existing drug safety assessment pipelines.

Different differences: The use of ‘genetic ancestry’ versus race in biomedical human genetic research

PubMed Central

Fujimura, Joan H.; Rajagopalan, Ramya

2011-01-01

This article presents findings from our ethnographic research on biomedical scientists’ studies of human genetic variation and common complex disease. We examine the socio-material work involved in genome-wide association studies (GWAS) and discuss whether, how, and when notions of race and ethnicity are or are not used. We analyze how researchers produce simultaneously different kinds of populations and population differences. Although many geneticists use race in their analyses, we find some who have invented a statistical genetics method and associated software that they use specifically to avoid using categories of race in their genetics analysis. Their method allows them to operationalize their concept of ‘genetic ancestry’ without resorting to notions of race and ethnicity. We focus on the construction and implementation of the software’s algorithms, and discuss the consequences and implications of the software technology for debates and policies around the use of race in genetics research. We also demonstrate that the production and use of their method involves a dynamic and fluid assemblage of actors in various disciplines responding to disciplinary and sociopolitical contexts and concerns. This assemblage also includes particular discourses on human history and geography as they become entangled with research on genetic markers and disease. We introduce the concept of ‘genome geography’, to analyze how some researchers studying human genetic variation ‘locate’ stretches of DNA in different places and times. The concept of genetic ancestry and the practice of genome geography rely on old discourses, but they also incorporate new technologies, infrastructures, and political and scientific commitments. Some of these new technologies provide opportunities to change some of our institutional and cultural forms and frames around notions of difference and similarity. Neverthless, we also highlight the slipperiness of genome geography and the tenacity of race and race concepts. PMID:21553638

Using Literature To Teach Geography in High Schools. ERIC Digest.

ERIC Educational Resources Information Center

Hume, Susan E.

This digest discusses various ways in which literature can be incorporated with world geography to make better connections across the curriculum. Reasons to use a literature-based approach to teach geography include: (1) there is a natural link between geography and literature; (2) the study of literature improves comprehension of geography; and…

Geography Textbook Assessment for Middle and High School Educators.

ERIC Educational Resources Information Center

Martin, Curtis M.

This geography textbook assessment is a tool and a guide for teachers and curriculum administrators who are responsible for adopting classroom geography materials. The assessment's goal is to help teachers identify the geography textbooks that are most compatible with the content goals of the geography education reform movement as stated in "The…

How Are Non-Geography Majors Motivated in a Large Introductory World Geography Course?

ERIC Educational Resources Information Center

Park, Seung Won; Huynh, Niem Tu

2015-01-01

University students who do not declare geography as their major are at risk of poor motivation to learn in an introductory geography class. However, research exploring the role of non-majors' motivation is lacking. This study examines motivational factors impacting non-geography students' engagement and performance. The findings suggest that…

Master's Theses in Geography: American and Canadian Universities. A Bibliography.

ERIC Educational Resources Information Center

Stuart, Merrill M.

The bibliography cites over 5,000 master's theses completed in geography departments in the United States and Canada through 1972. The theses are arranged by author within one of the following categories: (1) agricultural geography; (2) association of man and environment; (3) climatology; (4) cultural geography; (5) educational geography; (6)…

Geography 222 -- Issues in Economic Geography; Course Notes: Issues and Landscapes, [Introduction.

ERIC Educational Resources Information Center

Hurst, Eliot M. E.

In his introduction to the course, Issues in Economic Geography, the author surveys the profession of geography, reviewing its history and its function in today's society and making recommendations for a "rethinking" of geography. He states that positivism, the search for emperically verifiable knowledge that makes an objective science of some…

The Rise of Applied Geography.

ERIC Educational Resources Information Center

Philpponneau, Michel

1981-01-01

Presents an historical overview of the use of the science of geography for practical purposes. Topics discussed include British schools of geography during the 19th century, contributions of many of the founders of applied geography, forms in which geographical work can be used for practical purposes, and the status of applied geography in various…

Recent Trends in Geography Education in Louisiana

ERIC Educational Resources Information Center

Rohli, Robert V.; Binford, Paul E.

2016-01-01

Geography at elementary and middle schools in Louisiana, USA., remains a social studies strand along with civics, economics, and history, with no state-required geography course at any level. But because schools may require more geography than the state standard, this research examines the extent to which K-12 students are exposed to geography in…

Geography Teachers' Views on Effective Geography Teaching

ERIC Educational Resources Information Center

Kocalar, Ali Osman; Demirkaya, Hilmi

2017-01-01

Geography teaching is fulfilled within the frame of a specific curriculum and in order to achieve some acquirements in Turkey. Though there are course books prepared in accordance with the curriculum and activities in order to achieve the acquirements in geography teaching, they are geography teachers who will coordinate and fulfill the curriculum…

"GFL2"! The Updated "Geography for Life: National Geography Standards, Second Edition"

ERIC Educational Resources Information Center

Heffron, Susan Gallagher

2012-01-01

"Geography for Life: National Geography Standards, Second Edition" ("GFL2") is the recently released update of the original edition published in 1994. The original edition of "Geography for Life" provided excellent guidance on geographic content for teachers, curriculum designers, publishers, and pre-service teachers as well as many other…

Urban Geography: Topics in Geography, Number 1.

ERIC Educational Resources Information Center

National Council for Geographic Education.

The scope, objectives, and some of the findings of urban geography are discussed in this paper. Curriculum development in urban geography at the high-school level is also briefly described. The first of six articles, "Aspects and Trends of Urban Geography," explains the urban geographer's interest in internal city structure, interaction of static…

Teaching Geography in American History. ERIC Trends/Issues, Paper No. 1.

ERIC Educational Resources Information Center

Backler, Alan

This ERIC Trends Issues paper highlights the complementary qualities of geography and history and recommends the infusion of geography core themes into high school U.S. history courses. Part 1, "Rationale for Teaching Geography in American History," features information about: (1) overcoming the neglect of geography instruction; (2)…

Geography Teachers' Metaphors Concerning the Concept of "Geography"

ERIC Educational Resources Information Center

Sagdic, Mustafa

2013-01-01

The purpose of the present study is to reveal geography teachers' perception on the concept of "Geography", by means of the metaphors they use. The study was participated by 116 geography teachers working in several high-schools in Istanbul City center within the 2012-2013 academic year. Answers to the following questions were sought in…

Molecular characterization and specific detection of Anaplasma species (AP-sd) in sika deer and its first detection in wild brown bears and rodents in Hokkaido, Japan.

PubMed

Moustafa, Mohamed Abdallah Mohamed; Lee, Kyunglee; Taylor, Kyle; Nakao, Ryo; Sashika, Mariko; Shimozuru, Michito; Tsubota, Toshio

2015-12-01

A previously undescribed Anaplasma species (herein referred to as AP-sd) has been detected in sika deer, cattle and ticks in Japan. Despite being highly similar to some strains of A. phagocytophilum, AP-sd has never been detected in humans. Its ambiguous epidemiology and the lack of tools for its specific detection make it difficult to understand and interpret the prevalence of this Anaplasma species. We developed a method for specific detection, and examined AP-sd prevalence in Hokkaido wildlife. Our study included 250 sika deer (Cervus nippon yesoensis), 13 brown bears (Ursus arctos yesoensis) and 252 rodents including 138 (Apodemus speciosus), 45 (Apodemus argenteus), 42 (Myodes rufocanus) and 27 (Myodes rutilus) were collected from Hokkaido island, northern Japan, collected during 2010 to 2015. A 770 bp and 382 bp segment of the 16S rRNA and gltA genes, respectively, were amplified by nested PCR. Results were confirmed by cloning and sequencing of the positive PCR products. A reverse line blot hybridization (RLB) based on the 16S rRNA gene was then developed for the specific detection of AP-sd. The prevalence of AP-sd by nested PCR in sika deer was 51% (128/250). We detected this Anaplasma sp. for the first time in wild brown bears and rodents with a prevalence of 15% (2/13) and 2.4% (6/252), respectively. The sequencing results of the 16S rRNA and gltA gene amplicons were divergent from the selected A. phagocytophilum sequences in GenBank. Using a newly designed AP-sd specific probe for RLB has enabled us to specifically detect this Anaplasma species. Besides sika deer and cattle, wild brown bears and rodents were identified as potential reservoir hosts for AP-sd. This study provided a high throughput molecular method that specifically detects AP-sd, and which can be used to investigate its ecology and its potential as a threat to humans in Japan. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibitors of the Diadenosine Tetraphosphate Phosphorylase Rv2613c of Mycobacterium tuberculosis.

PubMed

Götz, Kathrin H; Hacker, Stephan M; Mayer, Daniel; Dürig, Jan-Niklas; Stenger, Steffen; Marx, Andreas

2017-10-20

The intracellular concentration of diadenosine tetraphospate (Ap 4 A) increases upon exposure to stress conditions. Despite being discovered over 50 years ago, the cellular functions of Ap 4 A are still enigmatic. If and how the varied Ap 4 A is a signal and involved in the signaling pathways leading to an appropriate cellular response remain to be discovered. Because the turnover of Ap 4 A by Ap 4 A cleaving enzymes is rapid, small molecule inhibitors for these enzymes would provide tools for the more detailed study of the role of Ap 4 A. Here, we describe the development of a high-throughput screening assay based on a fluorogenic Ap 4 A substrate for the identification and optimization of small molecule inhibitors for Ap 4 A cleaving enzymes. As proof-of-concept we screened a library of over 42 000 compounds toward their inhibitory activity against the Ap 4 A phosphorylase (Rv2613c) of Mycobacterium tuberculosis (Mtb). A sulfanylacrylonitril derivative with an IC 50 of 260 ± 50 nM in vitro was identified. Multiple derivatives were synthesized to further optimize their properties with respect to their in vitro IC 50 values and their cytotoxicity against human cells (HeLa). In addition, we selected two hits to study their antimycobacterial activity against virulent Mtb to show that they might be candidates for further development of antimycobacterial agents against multidrug-resistant Mtb.

A Novel Method for Constructing a WIFI Positioning System with Efficient Manpower

PubMed Central

Du, Yuanfeng; Yang, Dongkai; Xiu, Chundi

2015-01-01

With the rapid development of WIFI technology, WIFI-based indoor positioning technology has been widely studied for location-based services. To solve the problems related to the signal strength database adopted in the widely used fingerprint positioning technology, we first introduce a new system framework in this paper, which includes a modified AP firmware and some cheap self-made WIFI sensor anchors. The periodically scanned reports regarding the neighboring APs and sensor anchors are sent to the positioning server and serve as the calibration points. Besides the calculation of correlations between the target points and the neighboring calibration points, we take full advantage of the important but easily overlooked feature that the signal attenuation model varies in different regions in the regression algorithm to get more accurate results. Thus, a novel method called RSSI Geography Weighted Regression (RGWR) is proposed to solve the fingerprint database construction problem. The average error of all the calibration points’ self-localization results will help to make the final decision of whether the database is the latest or has to be updated automatically. The effects of anchors on system performance are further researched to conclude that the anchors should be deployed at the locations that stand for the features of RSSI distributions. The proposed system is convenient for the establishment of practical positioning system and extensive experiments have been performed to validate that the proposed method is robust and manpower efficient. PMID:25868078

A novel method for constructing a WIFI positioning system with efficient manpower.

PubMed

Du, Yuanfeng; Yang, Dongkai; Xiu, Chundi

2015-04-10

With the rapid development of WIFI technology, WIFI-based indoor positioning technology has been widely studied for location-based services. To solve the problems related to the signal strength database adopted in the widely used fingerprint positioning technology, we first introduce a new system framework in this paper, which includes a modified AP firmware and some cheap self-made WIFI sensor anchors. The periodically scanned reports regarding the neighboring APs and sensor anchors are sent to the positioning server and serve as the calibration points. Besides the calculation of correlations between the target points and the neighboring calibration points, we take full advantage of the important but easily overlooked feature that the signal attenuation model varies in different regions in the regression algorithm to get more accurate results. Thus, a novel method called RSSI Geography Weighted Regression (RGWR) is proposed to solve the fingerprint database construction problem. The average error of all the calibration points' self-localization results will help to make the final decision of whether the database is the latest or has to be updated automatically. The effects of anchors on system performance are further researched to conclude that the anchors should be deployed at the locations that stand for the features of RSSI distributions. The proposed system is convenient for the establishment of practical positioning system and extensive experiments have been performed to validate that the proposed method is robust and manpower efficient.

Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug's cardiac ion channel profile☆

PubMed Central

Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K.; Lukacs, Peter; Gawali, Vaibhavkumar S.; Todt, Hannes; Hilber, Karlheinz; Sandtner, Walter

2013-01-01

The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Nav1.5 sodium and Cav1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (≥ 10 μM) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. PMID:23707769

Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: a study to assess the drug's cardiac ion channel profile.

PubMed

Koenig, Xaver; Kovar, Michael; Rubi, Lena; Mike, Agnes K; Lukacs, Peter; Gawali, Vaibhavkumar S; Todt, Hannes; Hilber, Karlheinz; Sandtner, Walter

2013-12-01

The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licensed as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Nav1.5 sodium and Cav1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (≥ 10 μM) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

The Role of the Clathrin Adaptor AP-1: Polarized Sorting and Beyond

PubMed Central

Nakatsu, Fubito; Hase, Koji; Ohno, Hiroshi

2014-01-01

The selective transport of proteins or lipids by vesicular transport is a fundamental process supporting cellular physiology. The budding process involves cargo sorting and vesicle formation at the donor membrane and constitutes an important process in vesicular transport. This process is particularly important for the polarized sorting in epithelial cells, in which the cargo molecules need to be selectively sorted and transported to two distinct destinations, the apical or basolateral plasma membrane. Adaptor protein (AP)-1, a member of the AP complex family, which includes the ubiquitously expressed AP-1A and the epithelium-specific AP-1B, regulates polarized sorting at the trans-Golgi network and/or at the recycling endosomes. A growing body of evidence, especially from studies using model organisms and animals, demonstrates that the AP-1-mediated polarized sorting supports the development and physiology of multi-cellular units as functional organs and tissues (e.g., cell fate determination, inflammation and gut immune homeostasis). Furthermore, a possible involvement of AP-1B in the pathogenesis of human diseases, such as Crohn’s disease and cancer, is now becoming evident. These data highlight the significant contribution of AP-1 complexes to the physiology of multicellular organisms, as master regulators of polarized sorting in epithelial cells. PMID:25387275

Meeting the Challenge of Systemic Change in Geography Education: Lucy Sprague Mitchell's Young Geographers

ERIC Educational Resources Information Center

Downs, Roger M.

2016-01-01

The history of K-12 geography education has been characterized by recurrent high hopes and dashed expectations. There have, however, been moments when the trajectory of geography education might have changed to offer students the opportunity to develop a thorough working knowledge of geography. Lucy Sprague Mitchell's geography program developed…

The Ideas of Geography Teachers about In-Service Geography Training Activities

ERIC Educational Resources Information Center

Koc, Hakan

2013-01-01

The aim of the study is to evaluate the geography workshop (new approaches and new knowledge in geography), in view of the teachers, conducted within the in-service training activities for the geography teachers working in Sivas and Erzurum. The questionnaire, used as the data collection tool, was developed by the researcher. The questionnaire…

Geography Teachers' Concepts of Working with Thinking through Geography Strategies--Results of an Empirical Reconstructive Study

ERIC Educational Resources Information Center

Applis, Stefan

2016-01-01

The educational standards in geography in the German-speaking world separately refer to the areas of competence of judgment and evaluation and thus attach outstanding importance to reflective value orientation in geography classes. The tasks and challenges that arise from that for geography teachers will be investigated in a…

Information Geography: A Bridge between Engineering and the Social Sciences

ERIC Educational Resources Information Center

Paradiso, Maria

2006-01-01

This paper presents the metaphor of engineering and the social sciences located on either side of a chasm and connected by the bridge of information geography. Information geography is not an integral part of engineering and is a new field within geography, a social science discipline. The specialty of information geography is one of the newest in…

Does the High School Geography Experience Influence Enrollment in University Geography Courses?

ERIC Educational Resources Information Center

Leydon, Joseph; McLaughlin, Christina; Wilson, Heather

2017-01-01

The literature suggests that owing to profound difficulties with high school geography curricula, teachers play a vital role in stimulating student interest and in providing a platform for continuation in the study of geography at university. Yet, with little empirical evidence offered in support, it is unclear why students select geography at…

What Is Innovative Geography Teaching? A Perspective from Geography Teachers

ERIC Educational Resources Information Center

Artvinli, Eyüp

2017-01-01

The purpose of the study is to examine views of geography teachers on innovative geography teaching. The study group consists of 15 geography teachers (8 Females, 7 Males). The study is designed in keeping with phenomenological research. Semi-structured interview form is used as a data collection tool in the study. The collected data are analyzed…

Taking Stock in Geography Education around the World: An International Perspective on the Teaching of Geography

ERIC Educational Resources Information Center

DaSilva, Edmar Bernardes; Kvasnak, Robb Neil

2011-01-01

The identity of geography as a discipline since the nineteenth-century naissance of contemporary academia, if not before, has been often disputed. In higher education, geography is often part of the geosciences, often located in a geography, geology, earth science, and environmental science department or departments. In the world of education…

Transport of IRW, an ovotransferrin-derived antihypertensive peptide, in human intestinal epithelial Caco-2 cells.

PubMed

Bejjani, Satyanarayana; Wu, Jianping

2013-02-20

IRW is an egg ovotransferrin-derived ACE inhibitory peptide. The purpose of this study was to evaluate the stability and transcellular transport of IRW in Caco-2 cell monolayers. The stability of IRW was monitored on the apical (AP) surface while its transport was studied from AP to basal (BL) and from BL to AP surfaces. The results revealed that IRW is resistant against intestinal peptidase up to 60 min. Transport of IRW was not affected by addition of wortamanin, a transcytosis inhibitor. However, in the presence of cytochalasin D, a gap junction disruptor, transport of IRW was significantly increased, suggesting a possible passive transport from AP to BL surface. A higher transport of IRW from AP to BL surface than that from BL to AP surface suggests a passive-mediated transport. Moreover, in the presence of glycyl-sarcosine, a substrate for peptide transporter PepT 1, transport of IRW was reduced from AP to BL surface. The above observations showed atypical transport of IRW in Caco-2 cell monolayers. Thus, IRW may possibly be absorbed intact into the site of action for controlling hypertension.

BLOC-1 Interacts with BLOC-2 and the AP-3 Complex to Facilitate Protein Trafficking on Endosomes

PubMed Central

Di Pietro, Santiago M.; Falcón-Pérez, Juan M.; Tenza, Danièle; Setty, Subba R.G.; Marks, Michael S.; Raposo, Graça

2006-01-01

The adaptor protein (AP)-3 complex is a component of the cellular machinery that controls protein sorting from endosomes to lysosomes and specialized related organelles such as melanosomes. Mutations in an AP-3 subunit underlie a form of Hermansky-Pudlak syndrome (HPS), a disorder characterized by abnormalities in lysosome-related organelles. HPS in humans can also be caused by mutations in genes encoding subunits of three complexes of unclear function, named biogenesis of lysosome-related organelles complex (BLOC)-1, -2, and -3. Here, we report that BLOC-1 interacts physically and functionally with AP-3 to facilitate the trafficking of a known AP-3 cargo, CD63, and of tyrosinase-related protein 1 (Tyrp1), a melanosomal membrane protein previously thought to traffic only independently of AP-3. BLOC-1 also interacts with BLOC-2 to facilitate Tyrp1 trafficking by a mechanism apparently independent of AP-3 function. Both BLOC-1 and -2 localize mainly to early endosome-associated tubules as determined by immunoelectron microscopy. These findings support the idea that BLOC-1 and -2 represent hitherto unknown components of the endosomal protein trafficking machinery. PMID:16837549

Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus.

PubMed

Mutso, Margit; Morro, Ainhoa Moliner; Smedberg, Cecilia; Kasvandik, Sergo; Aquilimeba, Muriel; Teppor, Mona; Tarve, Liisi; Lulla, Aleksei; Lulla, Valeria; Saul, Sirle; Thaa, Bastian; McInerney, Gerald M; Merits, Andres; Varjak, Margus

2018-04-27

Infection by Chikungunya virus (CHIKV) of the Old World alphaviruses (family Togaviridae) in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP) (nsP1, nsp2, nsP3 and nsP4) that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD) of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV) harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3.

Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration

PubMed Central

Dubos, Aline; Castells-Nobau, Anna; Meziane, Hamid; Oortveld, Merel A.W.; Houbaert, Xander; Iacono, Giovanni; Martin, Christelle; Mittelhaeuser, Christophe; Lalanne, Valérie; Kramer, Jamie M.; Bhukel, Anuradha; Quentin, Christine; Slabbert, Jan; Verstreken, Patrik; Sigrist, Stefan J.; Messaddeq, Nadia; Birling, Marie-Christine; Selloum, Mohammed; Stunnenberg, Henk G.; Humeau, Yann; Schenck, Annette; Herault, Yann

2015-01-01

ATP6AP2, an essential accessory component of the vacuolar H+ ATPase (V-ATPase), has been associated with intellectual disability (ID) and Parkinsonism. ATP6AP2 has been implicated in several signalling pathways; however, little is known regarding its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional knockdowns of ATP6AP2 in the nervous system of Drosophila and mouse models. In Drosophila, ATP6AP2 knockdown induced defective phototaxis and vacuolated photoreceptor neurons and pigment cells when depleted in eyes and altered short- and long-term memory when depleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2Camk2aCre/0 mice) caused increased spontaneous locomotor activity and altered fear memory. Both Drosophila ATP6AP2 knockdown and Atp6ap2Camk2aCre/0 mice presented with presynaptic transmission defects, and with an abnormal number and morphology of synapses. In addition, Atp6ap2Camk2aCre/0 mice showed autophagy defects that led to axonal and neuronal degeneration in the cortex and hippocampus. Surprisingly, axon myelination was affected in our mutant mice, and axonal transport alterations were observed in Drosophila. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2Camk2aCre/0 mouse hippocampi revealed dysregulation of genes involved in myelination, action potential, membrane-bound vesicles and motor behaviour. In summary, ATP6AP2 disruption in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. PMID:26376863

Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration.

PubMed

Dubos, Aline; Castells-Nobau, Anna; Meziane, Hamid; Oortveld, Merel A W; Houbaert, Xander; Iacono, Giovanni; Martin, Christelle; Mittelhaeuser, Christophe; Lalanne, Valérie; Kramer, Jamie M; Bhukel, Anuradha; Quentin, Christine; Slabbert, Jan; Verstreken, Patrik; Sigrist, Stefan J; Messaddeq, Nadia; Birling, Marie-Christine; Selloum, Mohammed; Stunnenberg, Henk G; Humeau, Yann; Schenck, Annette; Herault, Yann

2015-12-01

ATP6AP2, an essential accessory component of the vacuolar H+ ATPase (V-ATPase), has been associated with intellectual disability (ID) and Parkinsonism. ATP6AP2 has been implicated in several signalling pathways; however, little is known regarding its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional knockdowns of ATP6AP2 in the nervous system of Drosophila and mouse models. In Drosophila, ATP6AP2 knockdown induced defective phototaxis and vacuolated photoreceptor neurons and pigment cells when depleted in eyes and altered short- and long-term memory when depleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2(Camk2aCre/0) mice) caused increased spontaneous locomotor activity and altered fear memory. Both Drosophila ATP6AP2 knockdown and Atp6ap2(Camk2aCre/0) mice presented with presynaptic transmission defects, and with an abnormal number and morphology of synapses. In addition, Atp6ap2(Camk2aCre/0) mice showed autophagy defects that led to axonal and neuronal degeneration in the cortex and hippocampus. Surprisingly, axon myelination was affected in our mutant mice, and axonal transport alterations were observed in Drosophila. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2(Camk2aCre/0) mouse hippocampi revealed dysregulation of genes involved in myelination, action potential, membrane-bound vesicles and motor behaviour. In summary, ATP6AP2 disruption in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. © The Author 2015. Published by Oxford University Press.

Tumor-targeting peptide conjugated pH-responsive micelles as a potential drug carrier for cancer therapy.

PubMed

Wu, Xiang Lan; Kim, Jong Ho; Koo, Heebeom; Bae, Sang Mun; Shin, Hyeri; Kim, Min Sang; Lee, Byung-Heon; Park, Rang-Woon; Kim, In-San; Choi, Kuiwon; Kwon, Ick Chan; Kim, Kwangmeyung; Lee, Doo Sung

2010-02-17

Herein, we prepared tumor-targeting peptide (AP peptide; CRKRLDRN) conjugated pH-responsive polymeric micelles (pH-PMs) in cancer therapy by active and pH-responsive tumor targeting delivery systems, simultaneously. The active tumor targeting and tumoral pH-responsive polymeric micelles were prepared by mixing AP peptide conjugated PEG-poly(d,l-lactic acid) block copolymer (AP-PEG-PLA) into the pH-responsive micelles of methyl ether poly(ethylene glycol) (MPEG)-poly(beta-amino ester) (PAE) block copolymer (MPEG-PAE). These mixed amphiphilic block copolymers were self-assembled to form stable AP peptide-conjugated and pH-responsive AP-PEG-PLA/MPEG-PAE micelles (AP-pH-PMs) with an average size of 150 nm. The AP-pH-PMs containing 10 wt % of AP-PEG-PLA showed a sharp pH-dependent micellization/demicellization transition at the tumoral acid pH. Also, they presented the pH-dependent drug release profile at the acidic pH of 6.4. The fluorescence dye, TRITC, encapsulated AP-pH-PMs (TRITC-AP-pH-PMs) presented the higher tumor-specific targeting ability in vitro cancer cell culture system and in vivo tumor-bearing mice, compared to control pH-responsive micelles of MPEG-PAE. For the cancer therapy, the anticancer drug, doxorubicin (DOX), was efficiently encapsulated into the AP-pH-PMs (DOX-AP-pH-PMs) with a higher loading efficiency. DOX-AP-pH-PMs efficiently deliver anticancer drugs in MDA-MB231 human breast tumor-bearing mice, resulted in excellent anticancer therapeutic efficacy, compared to free DOX and DOX encapsulated MEG-PAE micelles, indicating the excellent tumor targeting ability of AP-pH-PMs. Therefore, these tumor-targeting peptide-conjugated and pH-responsive polymeric micelles have great potential application in cancer therapy.

El Salvador: Conflict and Change: A Secondary Curriculum.

ERIC Educational Resources Information Center

Wilkens, Craig, Ed.

This curriculum emphasizes El Salvador's physical and human geography and involves students in active learning situations using critical and creative thinking skills. The seven lessons include: (1) "Why Study El Salvador?"; (2) "Where in the World Is El Salvador?"; (3) "Picturing El Salvador: Looking Beyond the…

Mapping of human autoantibody epitopes on aromatic L-amino acid decarboxylase.

PubMed

Candeloro, Paola; Voltattorni, Carla Borri; Perniola, Roberto; Bertoldi, Mariarita; Betterle, Corrado; Mannelli, Massimo; Giordano, Roberta; De Bellis, Annamaria; Tiberti, Claudio; Laureti, Stefano; Santeusanio, Fausto; Falorni, Alberto

2007-03-01

Aromatic l-amino acid decarboxylase (AADC) is target of autoantibodies in autoimmune polyendocrine syndrome I (APS I), especially in patients with autoimmune hepatitis. Little information is currently available on AADC autoantibody epitopes and on the interrelation between autoantibody-mediated inhibition of enzymatic activity and epitope specificity. We tested the immunoreactivity of full-length porcine AADC and of eight fragments of the enzyme with human serum from 18 patients with APS I, 199 with non-APS I autoimmune Addison's disease, 124 with type 1 diabetes mellitus, 36 with Graves' disease, and 141 healthy control subjects, and we evaluated the autoantibody-mediated enzymatic inhibition. AADC antibodies (Ab) were detected in 12 of 18 (67%) APS I patients and in six of 199 (3%) autoimmune Addison's disease patients. Four patients with autoimmune hepatitis were all positive for AADCAb. None of the 141 healthy control subjects, 82 patients with nonautoimmune adrenal insufficiency, 124 with type 1 diabetes mellitus, and 36 with Graves' disease were found positive. Two epitope regions, corresponding to amino acids 274-299 (E1) and 380-471 (E2) were identified. Localization of E1 was confirmed by displacement studies with synthetic peptides corresponding to peptides of porcine AADC. All 12 AADCAb-positive APS I sera reacted with E1, and seven of 12 (58%) reacted also with E2. E2-specific, but not E1-specific, autoantibodies were associated with a significant inhibition of in vitro AADC enzymatic activity. We mapped the human AADCAb epitopes to the middle and COOH-terminal regions of the enzyme. Autoantibodies to the COOH-terminal region induce a significant inhibition of enzymatic activity.

Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

PubMed Central

Calatrava-Ferreras, Lucía; Gonzalo-Gobernado, Rafael; Herranz, Antonio S.; Reimers, Diana; Montero Vega, Teresa; Jiménez-Escrig, Adriano; Richart López, Luis Alberto; Bazán, Eulalia

2012-01-01

Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders. PMID:23150735

Reconciling Discourse about Geography and Teaching Geography: The Case of Singapore Pre-Service Teachers

ERIC Educational Resources Information Center

Seow, Tricia

2016-01-01

This study draws upon a Foucauldian notion of discourse to explore how four pre-service geography teachers in Singapore made decisions about what geography is and how to enact their understandings of geography in their classrooms. This analysis of discursive power is particularly relevant to Singapore because of the high level of state control…

Recent Trends in Geography.

ERIC Educational Resources Information Center

Biddle, Don

1985-01-01

This article reports on current trends in geography instruction in Australia. It appeals for greater cooperation between "academic geographers" and geography teachers in the secondary schools. Concludes by voicing concern for improved geography instruction in the coming decade. (JDH)

Phosphoethanolamine Transferase LptA in Haemophilus ducreyi Modifies Lipid A and Contributes to Human Defensin Resistance In Vitro.

PubMed

Trombley, Michael P; Post, Deborah M B; Rinker, Sherri D; Reinders, Lorri M; Fortney, Kate R; Zwickl, Beth W; Janowicz, Diane M; Baye, Fitsum M; Katz, Barry P; Spinola, Stanley M; Bauer, Margaret E

2015-01-01

Haemophilus ducreyi resists the cytotoxic effects of human antimicrobial peptides (APs), including α-defensins, β-defensins, and the cathelicidin LL-37. Resistance to LL-37, mediated by the sensitive to antimicrobial peptide (Sap) transporter, is required for H. ducreyi virulence in humans. Cationic APs are attracted to the negatively charged bacterial cell surface. In other gram-negative bacteria, modification of lipopolysaccharide or lipooligosaccharide (LOS) by the addition of positively charged moieties, such as phosphoethanolamine (PEA), confers AP resistance by means of electrostatic repulsion. H. ducreyi LOS has PEA modifications at two sites, and we identified three genes (lptA, ptdA, and ptdB) in H. ducreyi with homology to a family of bacterial PEA transferases. We generated non-polar, unmarked mutants with deletions in one, two, or all three putative PEA transferase genes. The triple mutant was significantly more susceptible to both α- and β-defensins; complementation of all three genes restored parental levels of AP resistance. Deletion of all three PEA transferase genes also resulted in a significant increase in the negativity of the mutant cell surface. Mass spectrometric analysis revealed that LptA was required for PEA modification of lipid A; PtdA and PtdB did not affect PEA modification of LOS. In human inoculation experiments, the triple mutant was as virulent as its parent strain. While this is the first identified mechanism of resistance to α-defensins in H. ducreyi, our in vivo data suggest that resistance to cathelicidin LL-37 may be more important than defensin resistance to H. ducreyi pathogenesis.

Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity

PubMed Central

Gupta, Vinod K.; Paul, Sandip; Dutta, Chitra

2017-01-01

One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats—Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT). The review focuses on the general trend in the human microbiome evolution—a gradual transition in the gross compositional structure along with a continual decrease in diversity of the microbiome, especially of the gut microbiome, as the human populations passed through three stages of subsistence like foraging, rural farming and industrialized urban western life. In general, gut microbiome of the hunter-gatherer populations is highly abundant with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc., while those of the urban communities are often enriched in Bacteroides, Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most diverse among different populations, while respiratory tract and UGT microbiome show lesser variations. Higher microbiome diversity is observed for oral-cavity in hunter-gatherer group with higher prevalence of Haemophilus than agricultural group. In case of skin microbiome, rural and urban Chinese populations show variation in abundance of Trabulsiella and Propionibacterium. On the basis of published data, we have characterized the core microbiota—the set of genera commonly found in all populations, irrespective of their geographic locations, ethnicity or mode of subsistence. We have also identified the major factors responsible for geography-based alterations in microbiota; though it is not yet clear which factor plays a dominant role in shaping the microbiome—nature or nurture, host genetics or his environment. Some of the geographical/racial variations in microbiome structure have been attributed to differences in host genetics and innate/adaptive immunity, while in many other cases, cultural/behavioral features like diet, hygiene, parasitic load, environmental exposure etc. overshadow genetics. The ethnicity or population-specific variations in human microbiome composition, as reviewed in this report, question the universality of the microbiome-based therapeutic strategies and recommend for geographically tailored community-scale approaches to microbiome engineering. PMID:28690602

Aureobasidium pullulans produced β-glucan is effective to enhance Kurosengoku soybean extract induced Thrombospondin-1 expression.

PubMed

Muramatsu, Daisuke; Okabe, Mitsuyasu; Takaoka, Akinori; Kida, Hiroshi; Iwai, Atsushi

2017-06-06

Black yeast, Aureobasidium pullulans is extracellularly produced β-(1,3), (1,6)-D-glucan (β-glucan) under certain conditions. In this study, using Glycine max cv. Kurosengoku (Kurosengoku soybeans), the production of β-glucan through fermentation of A. pullulans was evaluated, and the effects of A. pullulans cultured fluid (AP-CF) containing β-glucan made with Kurosengoku soybeans (kAP-CF) on a human monocyte derived cell line, Mono Mac 6 cells were investigated. Concentration of β-glucan in kAP-CF reached the same level as normal AP-CF. An anti-angiogenic protein, Thrombospondin-1 (THBS1) was effectively induced after the stimulation with kAP-CF for comparison with AP-CF. The THBS1 is also induced after stimulation with hot water extract of Kurosengoku soybeans (KS-E), while the combined stimulation of β-glucan with KS-E more effectively induced THBS1 than that with KS-E alone. These results suggest effects of A. pullulans-produced β-glucan on the enhancement of Kurosengoku soybean-induced THBS1 expression.

Current direction-dependent modulation of human hand motor function by intermittent theta burst stimulation (iTBS).

PubMed

Shirota, Yuichiro; Dhaka, Suman; Paulus, Walter; Sommer, Martin

2017-05-22

Transcranial magnetic stimulation (TMS) with different current directions can activate different sets of neurons. Current direction can also affect the results of repetitive TMS. To test the influence of uni-directional intermittent theta burst stimulation (iTBS) using different current directions, namely posteroanterior (PA) and anteroposterior (AP), on motor behaviour. In a cross-over design, PA- and AP-iTBS was applied over the left primary motor cortex in 19 healthy, right-handed volunteers. Performance of a finger-tapping task was recorded before and 0, 10, 20, and 30min after the iTBS. The task was conducted with the right and left hands separately at each time point. As a control, AP-iTBS with reduced intensity was applied to 14 participants in a separate session (AP weak condition). The finger-tapping count with the left hand was decreased after PA-iTBS. Neither AP- nor AP weak -iTBS altered the performance. Current direction had a significant impact on the after-effects of iTBS. Copyright © 2017 Elsevier B.V. All rights reserved.

Metabolic fate of fenetylline in rat and man.

PubMed

Yoshimura, H; Yoshimitsu, T; Yamada, H; Koga, N; Oguri, K

1988-08-01

1. Metabolic fate of 7-[2-(alpha-methylphenylethylamino)ethyl]theophylline hydrochloride (fenetylline) was investigated in male Sprague-Dawley rats and three male volunteers. 2. Six metabolites were identified in the rat urine as amphetamine(AP), p-hydroxy-AP, acetylaminoethyl-theophylline(TP), aminoethyl-TP, hydroxyethyl-TP and carboxymethyl-TP by comparison of their spectral properties and h.p.l.c. and g.l.c. characteristics with those of authentic samples. All these metabolites was also detected in the urine of humans receiving fenetylline. 3. Quantification of these metabolites using h.p.l.c. and g.l.c. showed that carboxymethyl-TP, p-hydroxy-AP and acetylaminoethyl-TP were the major metabolites in 0-24 h rat urine at 13.7%, 11.2% and 9.3% of dose, respectively. In men, carboxymethyl-TP(39-43% dose) and AP(23-33% dose) were the major metabolites in 0-48 h urine. 4. These results suggest that fenetylline metabolism proceeds via oxidative cleavage at two different sites to produce aminoethyl-TP and AP, respectively. The pathway producing AP predominates, in both man and rat, but is more predominant in the former.

A Teacher's Perspective of Geography: A School Subject for Today, Tomorrow, and for All Time

ERIC Educational Resources Information Center

MacLeod, Douglas G.

2014-01-01

In this article, a retired long-time geography teacher offers his perspective on what a geography teacher needs to keep in mind when teaching geography. The author notes that geography is a useful school subject because it helps young people make their way in the world by giving them some tools to become lifelong learners. The author encourages…

Who Lives on the Other Side of that Boundary: A Model of Geographic Thinking

ERIC Educational Resources Information Center

Schmidt, Sandra J.

2011-01-01

As a geography educator, it is hard to miss geography's bad rap. There is no shortage of stories and quizzes that show just how bad Americans are at geography and, by implication, how bad geography teachers are. What the public means when they say Americans don't know geography is that people cannot pinpoint countries/states on a map, cannot name…

The Best of Both Worlds: Blending History and Geography in the K-12 Curriculum.

ERIC Educational Resources Information Center

Boehm, Richard G.; Saxe, David Warren; Rutherford, David J.

This report shows how the study of U.S. history can be enriched by blending geography into the curriculum. Because the fields of history and geography have not been melded together in terms of curricula, often history is not taught in relation to geography and geography has tended to be taught primarily as location/place information. The report…

Geography Education: Applying Spatial Aspects to Everyday Life: American Association of Geographers Geography Education Specialty Group

ERIC Educational Resources Information Center

Wessell, Jonathan E.

2016-01-01

Throughout his career teaching geography, Johnathan Wessell has always stressed to his students that they already knew a lot about geography before they entered his classroom. He writes in this article that once he convinces his students of this, they begin to realize that geography is all around them, and that they, in turn, begin to shift their…

Topics in Hawaii's History: Resources and Lesson Plans for Secondary School Teachers.

ERIC Educational Resources Information Center

Odo, Franklin, Ed.; Kawamoto, Kevin, Ed.; McGregor, Davianna, Ed.

Twenty-nine teachers participated in a 4-week National Endowment for the Humanities institute which covered topics from pre-contact Hawaiian population estimates to formation of plantation workforces to contemporary sovereignty issues. The lessons the participants developed are divided into nine sections. Section 1, "Geography," contains…

Cartographic Methods for Determining the Qibla

ERIC Educational Resources Information Center

Kimerling, A. Jon

2002-01-01

Islam is an important topic in human and regional geography instruction, and major textbooks include maps showing Islam's core and rapid expansion diffusion, along with the number of pilgrims to Mecca from different countries. Determining the qibla, the sacred direction for daily prayer, and the distance to Mecca are additional topics that link…

From Workshop to Classroom: Bridging GIS Success

ERIC Educational Resources Information Center

Stonier, Francis; Hong, Jung Eun

2016-01-01

This article shares the first-time geographic information system (GIS) experiences of two advanced placement human geography classes. The teacher had participated in a summer GIS workshop and then brought those skills into her classroom for the students' benefit. Eighteen students shared their experiences researching their family history, working…

The Landscapes of Sherlock Holmes.

ERIC Educational Resources Information Center

Tuan, Yi-Fu

1985-01-01

By critically reading Conan Doyle's "Sherlock Holmes," geography students can learn about the major beliefs, values, and fears of late Victorian England. The geographical scope of the work is discussed, as well as what the work tells us about beliefs concerning nature, environmental influence, and human nature of the period. (RM)

Women and Environment: Subsistence Paradigms 1850-1950.

ERIC Educational Resources Information Center

Marburg, Sandra Lin

1984-01-01

Analyzes the analogy of associating men with culture and women with nature as a model of the sexes that became dominant in the nineteenth century as part of broader theories of society in American social science, especially cultural anthropology and human geography. Suggests further studies based on female-oriented typologies. (BC)

Tsunesaburo Makiguchi: Introduction to the Man, His Ideas, and the Special Issue

ERIC Educational Resources Information Center

Goulah, Jason; Gebert, Andrew

2009-01-01

This article introduces the life and work of Tsunesaburo Makiguchi (1871-1944), a Japanese teacher, school principal, educational philosopher, author, activist, and Buddhist war resister. Quite likely, readers are unfamiliar with Tsunesaburo Makiguchi or his ideas. His writings on education covered three main areas, human geography, community…

Production and Space. The Global System, Level 3.

ERIC Educational Resources Information Center

Spicer, Brian, Ed.; And Others

Part of a geography series which stresses understanding of the environment through mastery of specific skills and concepts, the secondary level textbook investigates the interrelationships between humans and the goods they produce. The book is presented in 26 chapters organized around five main themes: (1) agricultural production, (2)…

Neighborhood Comparisons of Dog-Related Health Hazards and Behavior.

ERIC Educational Resources Information Center

Meade, Melinda

1984-01-01

Undergraduate students increase their understanding of human geography and become aware of their community's health ecology by examining the degree and geographical pattern of dog-associated health hazards in Athens, Georgia, and by studying the behavioral patterns and attitudes of Athens's residents that might be causally related to these health…

A Study of Japan for the Intermediate Grades.

ERIC Educational Resources Information Center

Sauer, Susan

Arranged in outline form, this unit on Japan contains over 40 activities for intermediate grade students. Subjects covered are human and physical geography, social history, life style, communication and travel, occupations, recreation, art, education, government, and relations with the United States. Four to 10 activities are described under each…

Angelica polysaccharides inhibit the growth and promote the apoptosis of U251 glioma cells in vitro and in vivo.

PubMed

Zhang, Wen-Feng; Yang, Yan; Li, Xin; Xu, Da-Yan; Yan, Yu-Li; Gao, Qiao; Jia, Ai-Ling; Duan, Ming-Hua

2017-09-15

Angelica sinensis (Oliv) Diels (Apiaceae) is a traditional medicine that has been used for more than 2000 years in China. It exhibits various therapeutic effects including neuroprotective, anti-oxidant, anti-inflammatory, and immunomodulatory activities. Angelica polysaccharides (APs), bioactive constituents of Angelica have been shown to be responsible for these effects; however, the utility of APs for the treatment of glioma and their mechanism of action remain to be elucidated. In this study, we investigated the inhibitory effects of APs on a glioma cell line and their molecular mechanism of action. U251 cells were utilized to confirm the effects of APs on glioma. The human glioblastoma cell line U251 was utilized for both in vitro and in vivo models, in which we tested the effects of APs. Flow cytometry, gene expression analysis, western blotting, and MTT assays were used to elucidate the effects of APs on cell proliferation, cell cycle, and apoptosis. The results demonstrated that APs significantly inhibited the growth and proliferation of U251 cells and induced their apoptosis. Furthermore, APs effectively reduced the expression of several cell cycle regulators: cyclins D1, B, and E. The apoptosis suppressor protein Bcl-2 was also downregulated, and the expression of pro-apoptotic proteins Bax and cleaved-caspase-3 increased. Additionally, APs inhibited the transforming growth factor (TGF)-β signaling pathway and stimulated the expression of E-cadherin, thus prohibiting cell growth. In conclusion, the results indicate that APs attenuate the tumorigenicity of glioma cells and promote their apoptosis by suppressing the TGF-β signaling pathway. The present study therefore provides evidence of the inhibitory effects of APs against glioma progression, and proposes their potential application as alternative therapeutic agents for glioma. Copyright © 2017 Elsevier GmbH. All rights reserved.

Whatever Happened to Economic Geography?

ERIC Educational Resources Information Center

Fagan, Robert

1985-01-01

Maintains that economic geography is alive and well. Describes some of the challenges facing research in economic geography and highlights the changing approaches being applied to economic geography. Includes sections on structural change, economic reorganization, and internationalization of manufacturing and finances. (JDH)

A Teacher's Bookshelf: The Historical Geography of the United States.

ERIC Educational Resources Information Center

Danzer, Gerald A.

1993-01-01

Contends that historical geography helps teachers understand the link between history and geography. Presents an annotated bibliography of recommended geography books for teachers. Asserts that the most essential volume is an atlas of U.S. history. (CFR)

Genome-wide analysis of the emerging infection with Mycobacterium avium subspecies paratuberculosis in the Arabian camels (Camelus dromedarius).

PubMed

Ghosh, Pallab; Hsu, Chungyi; Alyamani, Essam J; Shehata, Maher M; Al-Dubaib, Musaad A; Al-Naeem, Abdulmohsen; Hashad, Mahmoud; Mahmoud, Osama M; Alharbi, Khalid B J; Al-Busadah, Khalid; Al-Swailem, Abdulaziz M; Talaat, Adel M

2012-01-01

Mycobacterium avium subspecies paratuberculosis (M. ap) is the causative agent of paratuberculosis or Johne's disease (JD) in herbivores with potential involvement in cases of Crohn's disease in humans. JD is spread worldwide and is economically important for both beef and dairy industries. Generally, pathogenic ovine strains (M. ap-S) are mainly found in sheep while bovine strains (M. ap-C) infect other ruminants (e.g. cattle, goat, deer), as well as sheep. In an effort to characterize this emerging infection in dromedary/Arabian camels, we successfully cultured M. ap from several samples collected from infected camels suffering from chronic, intermittent diarrhea suggestive of JD. Gene-based typing of isolates indicated that all isolates belong to sheep lineage of strains of M. ap (M. ap-S), suggesting a putative transmission from infected sheep herds. Screening sheep and goat herds associated with camels identified the circulation of this type in sheep but not goats. The current genome-wide analysis recognizes these camel isolates as a sub-lineage of the sheep strain with a significant number of single nucleotide polymorphisms (SNPs) between sheep and camel isolates (∼1000 SNPs). Such polymorphism could represent geographical differences among isolates or host adaptation of M. ap during camel infection. To our knowledge, this is the first attempt to examine the genomic basis of this emerging infection in camels with implications on the evolution of this important pathogen. The sequenced genomes of M. ap isolates from camels will further assist our efforts to understand JD pathogenesis and the dynamic of disease transmission across animal species.

Genome-Wide Analysis of the Emerging Infection with Mycobacterium avium Subspecies paratuberculosis in the Arabian Camels (Camelus dromedarius)

PubMed Central

Ghosh, Pallab; Hsu, Chungyi; Alyamani, Essam J.; Shehata, Maher M.; Al-Dubaib, Musaad A.; Al-Naeem, Abdulmohsen; Hashad, Mahmoud; Mahmoud, Osama M.; Alharbi, Khalid B. J.; Al-Busadah, Khalid; Al-Swailem, Abdulaziz M.; Talaat, Adel M.

2012-01-01

Mycobacterium avium subspecies paratuberculosis (M. ap) is the causative agent of paratuberculosis or Johne's disease (JD) in herbivores with potential involvement in cases of Crohn's disease in humans. JD is spread worldwide and is economically important for both beef and dairy industries. Generally, pathogenic ovine strains (M. ap-S) are mainly found in sheep while bovine strains (M. ap-C) infect other ruminants (e.g. cattle, goat, deer), as well as sheep. In an effort to characterize this emerging infection in dromedary/Arabian camels, we successfully cultured M. ap from several samples collected from infected camels suffering from chronic, intermittent diarrhea suggestive of JD. Gene-based typing of isolates indicated that all isolates belong to sheep lineage of strains of M. ap (M. ap-S), suggesting a putative transmission from infected sheep herds. Screening sheep and goat herds associated with camels identified the circulation of this type in sheep but not goats. The current genome-wide analysis recognizes these camel isolates as a sub-lineage of the sheep strain with a significant number of single nucleotide polymorphisms (SNPs) between sheep and camel isolates (∼1000 SNPs). Such polymorphism could represent geographical differences among isolates or host adaptation of M. ap during camel infection. To our knowledge, this is the first attempt to examine the genomic basis of this emerging infection in camels with implications on the evolution of this important pathogen. The sequenced genomes of M. ap isolates from camels will further assist our efforts to understand JD pathogenesis and the dynamic of disease transmission across animal species. PMID:22393374

Molecular cloning of Rab5 (ApRab5) in Aiptasia pulchella and its retention in phagosomes harboring live zooxanthellae.

PubMed

Chen, Ming-Chyuan; Cheng, Ying-Min; Hong, Min-Chang; Fang, Lee-Shing

2004-11-19

The intracellular association of symbiotic dinoflagellates (zooxanthellae) with marine cnidarians is the very foundation of the highly productive and diversified coral reef ecosystems. To reveal its underlying molecular mechanisms, we previously cloned ApRab7, a Rab7 homologue of the sea anemone Aiptasia pulchella, and demonstrated its selective exclusion from phagosomes containing live zooxanthellae, but not from those containing either dead or photosynthesis-impaired algae. In this study, Rab5 was characterized, due to its key role in endocytosis and phagocytosis acting upstream of Rab7. The Aiptasia Rab5 homologue (ApRab5) is 79.5% identical to human Rab5C and contains all Rab-specific signature motifs. Subcellular fractionation study showed that ApRab5 is mainly cytosolic. EGFP reporter and phagocytosis studies indicated that membrane-associated ApRab5 is present in early endocytic and phagocytic compartments, and is able to promote their fusion. Significantly, immunofluorescence study showed that the majority of phagosomes containing either resident or newly internalized live zooxanthellae were labeled with ApRab5, while those containing either heat-killed or photosynthesis-impaired algae were mostly negative for ApRab5 staining whereas the opposite was observed for ApRab7. We propose that active phagosomal retention of ApRab5 is part of the mechanisms employed by live zooxanthellae to: (1) persist inside their host cells and (2) exclude ApRab7 from their phagosomes, thereby, establishing and/or maintaining an endosymbiotic relationship with their cnidarian hosts.

Geography literacy can develop Geography skills for high school students: is it true?

NASA Astrophysics Data System (ADS)

Utami, W. S.; Zain, I. M.; Sumarmi

2018-01-01

The most important issue related to education in Indonesia is the low quality of student learning and competence. The basic thing that is important to be studied is the demands of 21st-century skills that are difficult to fulfil with the low competence of student learning. Low competence of student learning demonstrated by low capacity of scientific literacy includes geography literacy. Geography skills of Indonesian students are also low. It is shown from the students’ ability to use maps to describe and to analyze is low. The purpose of this study is to determine the correlation between the literacy skills of geography to develop geography skills of high school students in Surabaya. Written and performance tests were given to the sample of 29 high school students. The results of the tests we analyzed based on Geography literacy and its correlation to Geography skills in terms of the ability to use the media, map, and analyze the phenomenon of the geosphere. The results showed that the students who have low literacy geography have difficulty in using map.

Factor Xa Mediates Calcium Flux in Endothelial Cells and is Potentiated by Igg From Patients With Lupus and/or Antiphospholipid Syndrome.

PubMed

Artim-Esen, Bahar; Smoktunowicz, Natalia; McDonnell, Thomas; Ripoll, Vera M; Pericleous, Charis; Mackie, Ian; Robinson, Eifion; Isenberg, David; Rahman, Anisur; Ioannou, Yiannis; Chambers, Rachel C; Giles, Ian

2017-09-07

Factor (F) Xa reactive IgG isolated from patients with antiphospholipid syndrome (APS) display higher avidity binding to FXa with greater coagulant effects compared to systemic lupus erythematosus (SLE) non APS IgG. FXa signalling via activation of protease-activated receptors (PAR) leads to increased intracellular calcium (Ca 2+ ). Therefore, we measured alterations in Ca 2+ levels in human umbilical vein endothelial cells (HUVEC) following FXa-mediated PAR activation and investigated whether FXa reactive IgG from patients with APS or SLE/APS- alter these responses. We observed concentration-dependent induction of Ca 2+ release by FXa that was potentiated by APS-IgG and SLE/APS- IgG compared to healthy control subjects' IgG, and FXa alone. APS-IgG and SLE/APS- IgG increased FXa mediated NFκB signalling and this effect was fully-retained in the affinity purified anti-FXa IgG sub-fraction. Antagonism of PAR-1 and PAR-2 reduced FXa-induced Ca 2+ release. Treatment with a specific FXa inhibitor, hydroxychloroquine or fluvastatin significantly reduced FXa-induced and IgG-potentiated Ca 2+ release. In conclusion, PAR-1 and PAR-2 are involved in FXa-mediated intracellular Ca 2+ release in HUVEC and FXa reactive IgG from patients with APS and/or SLE potentiate this effect. Further work is required to explore the potential use of IgG FXa reactivity as a novel biomarker to stratify treatment with FXa inhibitors in these patients.

Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease

PubMed Central

Nakagawa, Naoki; Gomez, Ivan G.; Johnson, Bryce G.; Kameoka, Sei; Jack, Richard M.; Lupher, Mark L.; Gharib, Sina A.; Duffield, Jeremy S.

2016-01-01

Pentraxin-2 (PTX-2), also known as serum amyloid P component (SAP/APCS), is a constitutive, antiinflammatory, innate immune plasma protein whose circulating level is decreased in chronic human fibrotic diseases. Here we show that recombinant human PTX-2 (rhPTX-2) retards progression of chronic kidney disease in Col4a3 mutant mice with Alport syndrome, reducing blood markers of kidney failure, enhancing lifespan by 20%, and improving histological signs of disease. Exogenously delivered rhPTX-2 was detected in macrophages but also in tubular epithelial cells, where it counteracted macrophage activation and was cytoprotective for the epithelium. Computational analysis of genes regulated by rhPTX-2 identified the transcriptional regulator c-Jun along with its activator protein–1 (AP-1) binding partners as a central target for the function of rhPTX-2. Accordingly, PTX-2 attenuates c-Jun and AP-1 activity, and reduces expression of AP-1–dependent inflammatory genes in both monocytes and epithelium. Our studies therefore identify rhPTX-2 as a potential therapy for chronic fibrotic disease of the kidney and an important inhibitor of pathological c-Jun signaling in this setting. PMID:27942582

Using Geography To Integrate Science and Social Studies.

ERIC Educational Resources Information Center

Dircks, Henry

2002-01-01

Focuses on geography in secondary education, offering reasons why geography is becoming more popular in schools. Provides four activities that integrate science and social studies through geography. Includes topics such as ecological disasters, monsoons, the ozone layer, and global warming. (CMK)

Turkish Primary Students' Perceptions of Geography

ERIC Educational Resources Information Center

Senyurt, Secil

2014-01-01

This study provides an in-depth investigation of Turkish primary school students' perceptions of geography. Gender differences in students' perceptions of geography were investigated, including definitions of geography and its field of study. The findings showed that "landforms," "our geographical regions/Turkey,"…

Opinions and Self-Evaluation of the Students of Geography Department about the Applications of Cooperative Learning in Regional Geography Course

ERIC Educational Resources Information Center

Aydin, Fatih

2013-01-01

The aim of this study was to determine the opinions and self-evaluation of the students of Geography Department about the applications of Cooperative Learning in Regional Geography course. The study was carried out for twelve weeks with 76 students who are in the Department of Geography, Faculty of Arts, Karabuk University between 2011-12. In this…

The Information Revolution in Geography.

ERIC Educational Resources Information Center

Tikunov, Vladimir S.

1996-01-01

Describes a number of topics in geography that are effected by the multimedia information revolution. These include research in political geography, finance, and the geography of tourism and medicine. Considers new technologies assisting spatial modeling and visualization of data and their effects on these fields. (MJP)

Gene expression in obstetric antiphospholipid syndrome: a systematic review.

PubMed

Muhammad Aliff, M; Muhammad Shazwan, S; Nur Fariha, M M; Hayati, A R; Nur Syahrina, A R; Maizatul Azma, M; Nazefah, A H; Jameela, S; Asral Wirda, A A

2016-12-01

Antiphospholipid syndrome (APS) is a multisystem disease that may present as venous or arterial thrombosis and/or pregnancy complications with the presence of antiphospholipid antibodies. Until today, heterogeneity of pathogenic mechanism fits well with various clinical manifestations. Moreover, previous studies have indicated that genes are differentially expressed between normal and in the disease state. Hence, this study systematically searched the literature on human gene expression that was differentially expressed in Obstetric APS. Electronic search was performed until 31st March 2015 through PubMed and Embase databases; where the following Medical Subject Heading (MeSH) terms were used and they had been specified as the primary focus of the articles; gene, antiphospholipid, obstetric, and pregnancy in the title or abstract. From 502 studies retrieved from the search, only original publications that had performed gene expression analyses of human placental tissue that reported on differentially expressed gene in pregnancies with Obstetric APS were included. Two reviewers independently scrutinized the titles and the abstracts before examining the eligibility of studies that met the inclusion criteria. For each study; diagnostic criteria for APS, method for analysis, and the gene signature were extracted independently by two reviewers. The genes listed were further analysed with the DAVID and the KEGG pathways. Three eligible gene expression studies involving obstetric APS, comprising the datasets on gene expression, were identified. All three studies showed a reduction in transcript expression on PRL, STAT5, TF, DAF, ABCA1, and HBEGF in Obstetric APS. The high enrichment score for functionality in DAVID had been positive regulation of cell proliferation. Meanwhile, pertaining to the KEGG pathway, two pathways were associated with some of the listed genes, which were ErBb signalling pathway and JAK-STAT signalling pathway. Ultimately, studies on a genetic level have the potential to provide new insights into the regulation and to widen the basis for identification of changes in the mechanism of Obstetric APS.

Astragalus polysaccharide suppresses palmitate-induced apoptosis in human cardiac myocytes: the role of Nrf1 and antioxidant response

PubMed Central

Zhang, Ji; Gu, Jian-Yun; Chen, Zhi-Song; Xing, Kai-Chen; Sun, Bing

2015-01-01

Objective: Previous studies have shown that Astragalus polysaccharides (APS) can be used to ameliorate cardiotoxicity due to chemotherapy and improve the cardiac function. However, the mechanism by which APS mediate this effect is unclear. In the present study, the effects of APS, which suppressed ROS-mediated apoptosis through Nrf1 accumulation in human cardiac myocytes (HCMs), was investigated. Methods: The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining. Expression of genes and proteins were analyzed by real-time PCR and western blotting respectively. Nrf1 gene was overexpressed using a lentiviral expression vector in HCMs in vitro, in order to explore the mechanism by which the Nrf1 promoted cell growth. Results: CCK8 and Annexin V-PI double-labeling showed that PAL induced cell death in a concentration-dependent manner, and suppressed HCMs proliferation. The combination PAL with APS was significantly decreased the percentage of the early phase of apoptosis cells. ROS levels were increased in HCMs by exposure to PAL. APS treatment significantly inhibited generation of ROS in response to palmitate. Moreover, PAL administration significantly decreased the mRNA and proteins expression of Bcl-2 as well as increased the mRNA expression of BAX and the protein expression of caspase-3 and caspase-8 as compare to those of control group, but APS treatment could reverse PA-induced HCMs apoptosis. The levels of reactive oxygen species (ROS), which was an oxidative stress marker, was significantly increased in cardiomyocytes by exposure to PAL, but overexpressing Nrf1 could ameliorate ROS-induced cardiomyocyte toxicity and increase the expression of SOD1 and SOD2 in HCMs by overexpressing Nrf1. Conclusions: This study demonstrated that the PAL could induce HCMs apoptosis. However, APS could reverse PAL-induced cardiomyocyte toxicity, at least partially, through suppression ROS and Nrf1 accumulation in HCMs. PMID:26045757

Dexamethasone inhibits inflammatory response via down regulation of AP-1 transcription factor in human lung epithelial cells.

PubMed

Patil, Rajeshwari H; Naveen Kumar, M; Kiran Kumar, K M; Nagesh, Rashmi; Kavya, K; Babu, R L; Ramesh, Govindarajan T; Chidananda Sharma, S

2018-03-01

The production of inflammatory mediators by epithelial cells in inflammatory lung diseases may represent an important target for the anti-inflammatory effects of glucocorticoids. Activator protein-1 is a major activator of inflammatory genes and has been proposed as a target for inhibition by glucocorticoids. We have used human pulmonary type-II A549 cells to examine the effect of dexamethasone on the phorbol ester (PMA)/Lipopolysaccharide (LPS) induced pro-inflammatory cytokines and AP-1 factors. A549 cells were treated with and without PMA or LPS or dexamethasone and the cell viability and nitric oxide production was measured by MTT assay and Griess reagent respectively. Expression of pro-inflammatory cytokines and AP-1 factors mRNA were measured using semi quantitative RT-PCR. The PMA/LPS treated cells show significant 2-3 fold increase in the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8 and TNF-α), cyclo‑oxygenase-2 (COX-2) and specific AP-1 factors (c-Jun, c-Fos and Jun-D). Whereas, pretreatment of cells with dexamethasone significantly inhibited the LPS induced nitric oxide production and PMA/LPS induced mRNAs expression of above pro-inflammatory cytokines, COX-2 and AP-1 factors. Cells treated with dexamethasone alone at both the concentrations inhibit the mRNAs expression of IL-1β, IL-6 and TNF-α compared to control. Our study reveals that dexamethasone decreased the mRNAs expression of c-Jun and c-Fos available for AP-1 formation suggested that AP-1 is the probable key transcription factor involved in the anti-inflammatory activity of dexamethasone. This may be an important molecular mechanism of steroid action in asthma and other chronic inflammatory lung diseases which may be useful for treatment of lung inflammatory diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Astragalus polysaccharide suppresses palmitate-induced apoptosis in human cardiac myocytes: the role of Nrf1 and antioxidant response.

PubMed

Zhang, Ji; Gu, Jian-Yun; Chen, Zhi-Song; Xing, Kai-Chen; Sun, Bing

2015-01-01

Previous studies have shown that Astragalus polysaccharides (APS) can be used to ameliorate cardiotoxicity due to chemotherapy and improve the cardiac function. However, the mechanism by which APS mediate this effect is unclear. In the present study, the effects of APS, which suppressed ROS-mediated apoptosis through Nrf1 accumulation in human cardiac myocytes (HCMs), was investigated. The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining. Expression of genes and proteins were analyzed by real-time PCR and western blotting respectively. Nrf1 gene was overexpressed using a lentiviral expression vector in HCMs in vitro, in order to explore the mechanism by which the Nrf1 promoted cell growth. CCK8 and Annexin V-PI double-labeling showed that PAL induced cell death in a concentration-dependent manner, and suppressed HCMs proliferation. The combination PAL with APS was significantly decreased the percentage of the early phase of apoptosis cells. ROS levels were increased in HCMs by exposure to PAL. APS treatment significantly inhibited generation of ROS in response to palmitate. Moreover, PAL administration significantly decreased the mRNA and proteins expression of Bcl-2 as well as increased the mRNA expression of BAX and the protein expression of caspase-3 and caspase-8 as compare to those of control group, but APS treatment could reverse PA-induced HCMs apoptosis. The levels of reactive oxygen species (ROS), which was an oxidative stress marker, was significantly increased in cardiomyocytes by exposure to PAL, but overexpressing Nrf1 could ameliorate ROS-induced cardiomyocyte toxicity and increase the expression of SOD1 and SOD2 in HCMs by overexpressing Nrf1. This study demonstrated that the PAL could induce HCMs apoptosis. However, APS could reverse PAL-induced cardiomyocyte toxicity, at least partially, through suppression ROS and Nrf1 accumulation in HCMs.

Hair analysis for drugs of abuse. XVI. Disposition of fenethylline and its metabolite into hair and discrimination between fenethylline use and amphetamine use by hair analysis.

PubMed

Kikura, R; Nakahara, Y

1997-01-01

The incorporation tendency of fenethylline (FNT) and its metabolite into rat hair and the discrimination between FNT use and amphetamine (AP) use by hair analysis using gas chromatography-mass spectrometry with selected ion monitoring are described. After the intraperitoneal administrations of FNT to pigmented hairy rats (5 mg/kg/day, 10 days, n = 3), concentrations of FNT and its metabolite, AP, in the rat hair newly grown over 4 weeks were compared with area under the concentration versus time curves (AUCs) of the drugs in the rat plasma. The hair concentrations of FNT and AP were 52 +/- 1.4 and 4.9 +/- 0.6 ng/mg, whereas those of plasma AUCs were 55.9 +/- 23.1 and 22.3 +/- 4.9 micrograms.min/mL, respectively. The ratios of the hair concentrations to the AUCs of FNT tends to be highly incorporated into hair from suggests that FNT tends to be highly incorporated into hair from blood. The analytical method was applied to the determination of the metabolites in scalp hair of humans who were given FNT orally in multiple doses (50 mg/day, 3 days, n = 5) or in a single dose (50 mg/day, 1 day, n = 1). FNT and AP were detected at 0.51 +/- 0.23 and 0.35 +/- 0.12 ng/mg, respectively, in the proximal 1-cm hair segments from subjects given FNT orally for 3 days and 0.25 and 0.11 ng/mg, respectively, in the single-dose sample. In addition, it was found that the concentrations of FNT were 1.2 to 2.7 times greater than those of AP in the human hair samples, except for one sample, although FNT rapidly disappeared from the urine compared with AP. It was concluded that hair would be a good specimen for disclosure of drug history of FNT and for discrimination between FNT use and AP abuse.

Toward a Geography of the Negro

ERIC Educational Resources Information Center

Ritter, Fredric A.

1971-01-01

Within geography, Black America can best be studied in the geography of cities. Topics suggested include sources of data, urban sprawl, arrangement and support of cities, urban demography, urban land values, urban land uses, and especially the geography of the black community within the city. (NH)

A Comparative Analysis of Geography Education: International Samples and Turkey

ERIC Educational Resources Information Center

Incekara, Suleyman

2010-01-01

In today's world, the developments being experienced in geography education are focusing on issues like the following: integrating technology into geography courses, placing a comprehensive and integrative perspective regarding geography into the curriculum, stressing independent learning and team-learning simultaneously, educating students to…

E6AP is Required for Human Papillomavirus type 16 E6 to Cause Cervical Cancer in Mice

PubMed Central

Shai, Anny; Pitot, Henry C.; Lambert, Paul F.

2010-01-01

High-risk human papillomaviruses cause certain anogenital and head and neck cancers. E6, one of three potent HPV oncogenes that contribute to the development of these malignancies, is a multifunctional protein with many biochemical activities. Among these activities are its ability to bind and inactivate the cellular tumor suppressor p53, induce expression of telomerase, and bind to various other proteins including Bak, E6BP1, E6TP1, and proteins that contain PDZ domains such as hScrib and hDlg. Many of these activities are thought to contribute to E6’s role in carcinogenesis. E6’s interaction with many of these cellular proteins, including p53, leads to their destabilization. This property is mediated at least in part through E6’s ability to recruit the ubiquitin ligase, E6AP into complexes with these cellular proteins resulting in their ubiquitin–mediated degradation by the proteasome. In this study, we address the requirement for E6AP in mediating E6's acute and oncogenic phenotypes, including induction of epithelial hyperplasia, abrogation of DNA damage response and induction of cervical cancer. Loss of E6AP had no discernable effect on E6's ability to induce hyperplasia or abrogate DNA damage responses, akin to what we had earlier observed in the mouse epidermis. Nevertheless, in cervical carcinogenesis studies, there was a complete loss of E6’s oncogenic potential in mice nulligenic for E6AP. Thus, E6AP is absolutely required for E6 to cause cervical cancer. PMID:20530688

Benzylamine antihyperglycemic effect is abolished by AOC3 gene invalidation in mice but not rescued by semicarbazide-sensitive amine oxidase expression under the control of aP2 promoter.

PubMed

Grès, Sandra; Bour, Sandy; Valet, Philippe; Carpéné, Christian

2012-12-01

Semicarbazide-sensitive amine oxidase (SSAO) is a transmembrane enzyme that metabolizes primary amines from endogenous or dietary origin. SSAO is highly expressed in adipose, smooth muscle and endothelial cells. In each of these cell types, SSAO is implicated in different biological functions, such as glucose transport activation, extracellular matrix maturation and leucocyte extravasation, respectively. However, the physiological functions of SSAO and their involvement in pathogenesis remain uncompletely characterized. To better understand the role of adipose tissue SSAO, we investigated whether it was necessary and/or sufficient to produce the antihyperglycemic effect of the SSAO-substrate benzylamine, already reported in mice. Therefore, we crossed SSAO-deficient mice invalidated for AOC3 gene and transgenic mice expected to express human SSAO in an adipocyte-specific manner, under the control of aP2 promoter. The aP2-human AOC3 construct (aP2-hAOC3) was equally expressed in the adipose tissue of mice expressing or not the native murine form and almost absent in other tissues. However, the corresponding SSAO activity found in adipose tissue represented only 20 % that of control mice. As a consequence, the benzylamine antihyperglycemic effect observed during glucose tolerance test in control was abolished in AOC3-KO mice but not rescued in mice expressing aP2-hAOC3. The capacity of benzylamine or methylamine to activate glucose uptake in adipocytes exhibited parallel variations in the corresponding genotypes. Although the aP2-hAOC3 construct did not allow a total rescue of SSAO activity in adipose tissue, it could be assessed from our observations that adipocyte SSAO plays a pivotal role in the increased glucose tolerance promoted by pharmacological doses of benzylamine.

CdS/TiO2-fluorescein isothiocyanate nanoparticles as fluorescence resonance energy transfer probe for the determination of trace alkaline phosphatase based on affinity adsorption assay.

PubMed

Liu, Jia-Ming; Lin, Li-ping; Jiao, Li; Cui, Ma-Lin; Wang, Xin-Xing; Zhang, Li-Hong; Zheng, Zhi-Yong

2012-08-30

The CdS/TiO(2)-fluorescein isothiocyanate (FITC) luminescent nanoparticles (CdS/TiO(2)-FITC) with the particle size of 20 nm have been synthesized by sol-gel method. CdS/TiO(2)-FITC could emit the fluorescence of both FITC and CdS/TiO(2). The fluorescence resonance energy transfer (FRET) occurred between the donor CdS/TiO(2) and the acceptor FITC in the CdS/TiO(2)-FITC. Taking advantages of the excellent characteristics of FRET, a new CdS/TiO(2)-FITC FRET labeling reagent and a CdS/TiO(2)-FITC-wheat germ agglutinin (CdS/TiO(2)-FITC-WGA) fluorescent probe have been developed. The FRET occurring between the donor CdS/TiO(2) and the acceptor FITC in the labelled product CdS/TiO(2)-FITC-WGA-AP, formed in the affinity adsorption reaction between the WGA in this CdS/TiO(2)-FITC-WGA fluorescent probe and alkaline phosphatase (AP), sharply enhanced the fluorescence signal of FITC and quench the fluorescence signal of CdS/TiO(2). Moreover, the ΔF (the change of the fluorescence signal) of FITC and CdS/TiO(2) were proportional to the content of AP, respectively. Thus, a new method that CdS/TiO(2)-fluorescein isothiocyanate nanoparticles for the determination of trace AP based on FRET-affinity adsorption assay has been established. The limit of quantification (LOQ) of the method was 1.3×10(-17) g AP mL(-1) for CdS/TiO(2) and 1.1×10(-17) g AP mL(-1) for FITC, respectively. This sensitive, rapid, high selective and precise method has been applied to the determination of AP in human serum and the prediction of human disease with the results agreed well with enzyme-linked immunosorbent assay (ELISA) in Zhangzhou Municipal Hospital of Fujian Province. Simultaneously, the reaction mechanism for the determination of AP was also discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Analysis of class II (hydrolytic) and class I (beta-lyase) apurinic/apyrimidinic endonucleases with a synthetic DNA substrate.

PubMed Central

Levin, J D; Demple, B

1990-01-01

We have developed simple and sensitive assays that distinguish the main classes of apurinic/apyrimidinic (AP) endonucleases: Class I enzymes that cleave on the 3' side of AP sites by beta-elimination, and Class II enzymes that cleave by hydrolysis on the 5' side. The distinction of the two types depends on the use of a synthetic DNA polymer that contains AP sites with 5'-[32P]phosphate residues. Using this approach, we now show directly that Escherichia coli endonuclease IV and human AP endonuclease are Class II enzymes, as inferred previously on the basis of indirect assays. The assay method does not exhibit significant interference by nonspecific nucleases or primary amines, which allows the ready determination of different AP endonuclease activities in crude cell extracts. In this way, we show that virtually all of the Class II AP endonuclease activity in E. coli can be accounted for by two enzymes: exonuclease III and endonuclease IV. In the yeast Saccharomyces cerevisiae, the Class II AP endonuclease activity is totally dependent on a single enzyme, the Apn1 protein, but there are probably multiple Class I enzymes. The versatility and ease of our approach should be useful for characterizing this important class of DNA repair enzymes in diverse systems. PMID:1698278

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

PubMed Central

Dumnicka, Paulina; Maduzia, Dawid; Ceranowicz, Piotr; Olszanecki, Rafał; Drożdż, Ryszard; Kuśnierz-Cabala, Beata

2017-01-01

Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients. PMID:28208708

A review of research on ecosystem of arid area using RS-GIS in China

NASA Astrophysics Data System (ADS)

Han, Hongling

2007-06-01

Arid area is classical mountain-oasis-desert ecosystem in North-west China. As the ecosystem has its nature geography character obviously, it has superior to research with remote-sensing and geography information system. The study on arid ecosystem in RS-GIS' way is focused on that the landscape spatial pattern of complex MODS ecosystem, the dynamic development of Land use/land cover, the security of ecological environment of eco-tone and so on. At the same time, the research on the single system is more and more, which has provided more ways and deeper fields of arid area using RS-GIS. Through the use of RS-GIS, desertification, oasis' development, urbanization etc. can be known, which would provide precaution for human-being and suitable ways to adjust the problems.

Population flows in an international context.

PubMed

Regulska, J; Vural, L

1987-01-01

The authors feel that geography courses have been remiss in examining migration in its international context and in discussing its global implications. They have constructed this 6-lecture teaching module that addresses the economic, political, and social ramifications of international migration, in addition to the geographical dimension. The module is geared to undergraduate studies in human, social, or population geography, sociology, economics, and political science. Each of the lectures outlined includes special topics for emphasis, supplementary audiovisual materials, and suggested readings. Lectures include: 1) The Importance and Global Effects of International Population Flows; 2) Guest Workers -- Migration of People with Limited Skills; 3) Brain Drain -- Migration of Highly Skilled Professionals; 4) Political Causes of International Migration: Refugee Movement; 5) Refugee Women -- Displaced Majority; and 6) Comparison of Immigration and Refugee Policy in the US and Canada.

Applied Geography Internships: Operational Canadian Models.

ERIC Educational Resources Information Center

Foster, L. T.

1982-01-01

Anxious to maintain student enrollments, geography departments have placed greater emphasis on the applied nature of the discipline. Described are (1) the advantages of internships in college geography curricula that enable students to gain firsthand knowledge about the usefulness of geography in real world situations and (2) operational models…

The Geography for Life Standards and American Political Geography.

ERIC Educational Resources Information Center

Jones, Douglas Deane

1997-01-01

Explores the intersection of geography and politics in U.S. public policy development and connects this to several of the National Geography Standards. Discusses contemporary issues including economic interdependence, the impact of migration, resource competition, cultural values, and environmental issues. Offers suggested student activities. (MJP)

Returning "Region" to World Regional Geography

ERIC Educational Resources Information Center

Rees, Peter W.; Legates, Margaret

2013-01-01

World regional geography textbooks rarely focus on the process of region formation, despite frequent calls to reincorporate a regional approach to teaching global geography. An instructional strategy using problem-based learning in a small honors section of a large world regional geography course is described. Using a hypothetical scenario…

In Silico Analysis of Antibiotic Resistance Genes in the Gut Microflora of Individuals from Diverse Geographies and Age-Groups

PubMed Central

Ghosh, Tarini Shankar; Gupta, Sourav Sen; Nair, Gopinath Balakrish; Mande, Sharmila S.

2013-01-01

The spread of antibiotic resistance, originating from the rampant and unrestrictive use of antibiotics in humans and livestock over the past few decades has emerged as a global health problem. This problem has been further compounded by recent reports implicating the gut microbial communities to act as reservoirs of antibiotic resistance. We have profiled the presence of probable antibiotic resistance genes in the gut flora of 275 individuals from eight different nationalities. For this purpose, available metagenomic data sets corresponding to 275 gut microbiomes were analyzed. Sequence similarity searches of the genomic fragments constituting each of these metagenomes were performed against genes conferring resistance to around 240 antibiotics. Potential antibiotic resistance genes conferring resistance against 53 different antibiotics were detected in the human gut microflora analysed in this study. In addition to several geography/country-specific patterns, four distinct clusters of gut microbiomes, referred to as ‘Resistotypes’, exhibiting similarities in their antibiotic resistance profiles, were identified. Groups of antibiotics having similarities in their resistance patterns within each of these clusters were also detected. Apart from this, mobile multi-drug resistance gene operons were detected in certain gut microbiomes. The study highlighted an alarmingly high abundance of antibiotic resistance genes in two infant gut microbiomes. The results obtained in the present study presents a holistic ‘big picture’ on the spectra of antibiotic resistance within our gut microbiota across different geographies. Such insights may help in implementation of new regulations and stringency on the existing ones. PMID:24391833

Digitizing Patterns of Power - Cartographic Communication for Digital Humanities

NASA Astrophysics Data System (ADS)

Kriz, Karel; Pucher, Alexander; Breier, Markus

2018-05-01

The representation of space in medieval texts, the appropriation of land and the subsequent installation of new structures of power are central research topics of the project "Digitizing Patterns of Power" (DPP). The project focuses on three regional case studies: the Eastern Alps and the Morava-Thaya region, the historical region of Macedonia, and historical Southern Armenia. DPP is a multidisciplinary project, conducted by the Austrian Academy of Sciences the Institute for Medieval Research (IMAFO) in cooperation with the University of Vienna, Department of Geography and Regional Research. It is part of an initiative to promote digital humanities research in Austria. DPP brings together expertise from historical and archaeological research as well as cartography and geocommunication to explore medieval geographies. The communication of space, time and spatial interconnectivity is an essential aspect of DPP. By incorporating digital cartographic expertise, relevant facts can be depicted in a more effective visual form. Optimal cartographic visualization of base data as well as the historical and archaeological information in an interactive map-based online platform are important features. However, the multidisciplinary of the project presents the participants with various challenges. The different involved disciplines, among them cartography, archaeology and history each have their own approaches to relevant aspects of geography and geocommunication. This paper treats geocommunication characteristics and approaches to interactive mapping in a historical and archaeological context within a multidisciplinary project environment. The fundamental challenges of cartographic communication within DPP will be presented. Furthermore, recent results on the communication of historical topographic, as well as uncertain thematic content will be demonstrated.

PKC-dependent stimulation of the human MCT1 promoter involves transcription factor AP2.

PubMed

Saksena, Seema; Dwivedi, Alka; Gill, Ravinder K; Singla, Amika; Alrefai, Waddah A; Malakooti, Jaleh; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K

2009-02-01

Monocarboxylate transporter (MCT1) plays an important role in the absorption of short-chain fatty acids (SCFA) such as butyrate in the human colon. Previous studies from our laboratory have demonstrated that phorbol ester, PMA (1 microM, 24 h), upregulates butyrate transport and MCT1 protein expression in human intestinal Caco-2 cells. However, the molecular mechanisms involved in the transcriptional regulation of MCT1 gene expression by PMA in the intestine are not known. In the present study, we showed that PMA (0.1 microM, 24 h) increased the MCT1 promoter activity (-871/+91) by approximately fourfold. A corresponding increase in MCT1 mRNA abundance in response to PMA was also observed. PMA-induced stimulation of MCT1 promoter activity was observed as early as 1 h and persisted until 24 h, suggesting that the effects of PMA are attributable to initial PKC activation. Kinase inhibitor and phosphorylation studies indicated that these effects may be mediated through activation of the atypical PKC-zeta isoform. 5'-deletion studies demonstrated that the MCT1 core promoter region (-229/+91) is the PMA-responsive region. Site-directed mutagenesis studies showed the predominant involvement of potential activator protein 2 (AP2) binding site in the activation of MCT1 promoter activity by PMA. In addition, overexpression of AP2 in Caco-2 cells significantly increased MCT1 promoter activity in a dose-dependent manner. These findings showing the regulation of MCT1 promoter by PKC and AP2 are of significant importance for an understanding of the molecular regulation of SCFA absorption in the human intestine.

Human ex-vivo action potential model for pro-arrhythmia risk assessment.

PubMed

Page, Guy; Ratchada, Phachareeya; Miron, Yannick; Steiner, Guido; Ghetti, Andre; Miller, Paul E; Reynolds, Jack A; Wang, Ken; Greiter-Wilke, Andrea; Polonchuk, Liudmila; Traebert, Martin; Gintant, Gary A; Abi-Gerges, Najah

2016-01-01

While current S7B/E14 guidelines have succeeded in protecting patients from QT-prolonging drugs, the absence of a predictive paradigm identifying pro-arrhythmic risks has limited the development of valuable drug programs. We investigated if a human ex-vivo action potential (AP)-based model could provide a more predictive approach for assessing pro-arrhythmic risk in man. Human ventricular trabeculae from ethically consented organ donors were used to evaluate the effects of dofetilide, d,l-sotalol, quinidine, paracetamol and verapamil on AP duration (APD) and recognized pro-arrhythmia predictors (short-term variability of APD at 90% repolarization (STV(APD90)), triangulation (ADP90-APD30) and incidence of early afterdepolarizations at 1 and 2Hz to quantitatively identify the pro-arrhythmic risk. Each drug was blinded and tested separately with 3 concentrations in triplicate trabeculae from 5 hearts, with one vehicle time control per heart. Electrophysiological stability of the model was not affected by sequential applications of vehicle (0.1% dimethyl sulfoxide). Paracetamol and verapamil did not significantly alter anyone of the AP parameters and were classified as devoid of pro-arrhythmic risk. Dofetilide, d,l-sotalol and quinidine exhibited an increase in the manifestation of pro-arrhythmia markers. The model provided quantitative and actionable activity flags and the relatively low total variability in tissue response allowed for the identification of pro-arrhythmic signals. Power analysis indicated that a total of 6 trabeculae derived from 2 hearts are sufficient to identify drug-induced pro-arrhythmia. Thus, the human ex-vivo AP-based model provides an integrative translational assay assisting in shaping clinical development plans that could be used in conjunction with the new CiPA-proposed approach. Copyright © 2016 Elsevier Inc. All rights reserved.

Human ex-vivo action potential model for pro-arrhythmia risk assessment

PubMed Central

Page, Guy; Ratchada, Phachareeya; Miron, Yannick; Steiner, Guido; Ghetti, Andre; Miller, Paul E; Reynolds, Jack A; Wang, Ken; Greiter-Wilke, Andrea; Polonchuk, Liudmila; Traebert, Martin; Gintant, Gary A; Abi-Gerges, Najah

2016-01-01

While current S7B/E14 guidelines have succeeded in protecting patients from QT-prolonging drugs, the absence of a predictive paradigm identifying pro-arrhythmic risks has limited the development of valuable drug programs. We investigated if a human ex-vivo action potential (AP)-based model could provide a more predictive approach for assessing pro-arrhythmic risk in man. Human ventricular trabeculae from ethically consented organ donors were used to evaluate the effects of dofetilide, d,l-sotalol, quinidine, paracetamol and verapamil on AP duration (APD) and recognized pro-arrhythmia predictors (short-term variability of APD at 90% repolarization (STV(APD90)), triangulation (ADP90-APD30) and incidence of early afterdepolarizations at 1 and 2 Hz to quantitatively identify the pro-arrhythmic risk. Each drug was blinded and tested separately with 3 concentrations in triplicate trabeculae from 5 hearts, with one vehicle time control per heart. Electrophysiological stability of the model was not affected by sequential applications of vehicle (0.1% dimethyl sulfoxide). Paracetamol and verapamil did not significantly alter anyone of the AP parameters and were classified as devoid of pro-arrhythmic risk. Dofetilide, d,l-sotalol and quinidine exhibited an increase in the manifestation of pro-arrhythmia markers. The model provided quantitative and actionable activity flags and the relatively low total variability in tissue response allowed for the identification of pro-arrhythmic signals. Power analysis indicated that a total of 6 trabeculae derived from 2 hearts are sufficient to identify drug-induced pro-arrhythmia. Thus, the human ex-vivo AP-based model provides an integrative translational assay assisting in shaping clinical development plans that could be used in conjunction with the new CiPA-proposed approach. PMID:27235787

A New lncRNA, APTR, Associates with and Represses the CDKN1A/p21 Promoter by Recruiting Polycomb Proteins

PubMed Central

Negishi, Masamitsu; Wongpalee, Somsakul P.; Sarkar, Sukumar; Park, Jonghoon; Lee, Kyung Yong; Shibata, Yoshiyuki; Reon, Brian J.; Abounader, Roger; Suzuki, Yutaka; Sugano, Sumio; Dutta, Anindya

2014-01-01

Long noncoding RNAs (lncRNAs) have emerged as a major regulator of cell physiology, but many of which have no known function. CDKN1A/p21 is an important inhibitor of the cell-cycle, regulator of the DNA damage response and effector of the tumor suppressor p53, playing a crucial role in tumor development and prevention. In order to identify a regulator for tumor progression, we performed an siRNA screen of human lncRNAs required for cell proliferation, and identified a novel lncRNA, APTR, that acts in trans to repress the CDKN1A/p21 promoter independent of p53 to promote cell proliferation. APTR associates with the promoter of CDKN1A/p21 and this association requires a complementary-Alu sequence encoded in APTR. A different module of APTR associates with and recruits the Polycomb repressive complex 2 (PRC2) to epigenetically repress the p21 promoter. A decrease in APTR is necessary for the induction of p21 after heat stress and DNA damage by doxorubicin, and the levels of APTR and p21 are anti-correlated in human glioblastomas. Our data identify a new regulator of the cell-cycle inhibitor CDKN1A/p21 that acts as a proliferative factor in cancer cell lines and in glioblastomas and demonstrate that Alu elements present in lncRNAs can contribute to targeting regulatory lncRNAs to promoters. PMID:24748121

A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells.

PubMed

Gunhanlar, N; Shpak, G; van der Kroeg, M; Gouty-Colomer, L A; Munshi, S T; Lendemeijer, B; Ghazvini, M; Dupont, C; Hoogendijk, W J G; Gribnau, J; de Vrij, F M S; Kushner, S A

2018-05-01

Progress in elucidating the molecular and cellular pathophysiology of neuropsychiatric disorders has been hindered by the limited availability of living human brain tissue. The emergence of induced pluripotent stem cells (iPSCs) has offered a unique alternative strategy using patient-derived functional neuronal networks. However, methods for reliably generating iPSC-derived neurons with mature electrophysiological characteristics have been difficult to develop. Here, we report a simplified differentiation protocol that yields electrophysiologically mature iPSC-derived cortical lineage neuronal networks without the need for astrocyte co-culture or specialized media. This protocol generates a consistent 60:40 ratio of neurons and astrocytes that arise from a common forebrain neural progenitor. Whole-cell patch-clamp recordings of 114 neurons derived from three independent iPSC lines confirmed their electrophysiological maturity, including resting membrane potential (-58.2±1.0 mV), capacitance (49.1±2.9 pF), action potential (AP) threshold (-50.9±0.5 mV) and AP amplitude (66.5±1.3 mV). Nearly 100% of neurons were capable of firing APs, of which 79% had sustained trains of mature APs with minimal accommodation (peak AP frequency: 11.9±0.5 Hz) and 74% exhibited spontaneous synaptic activity (amplitude, 16.03±0.82 pA; frequency, 1.09±0.17 Hz). We expect this protocol to be of broad applicability for implementing iPSC-based neuronal network models of neuropsychiatric disorders.

Hydroxychloroquine protects the annexin A5 anticoagulant shield from disruption by antiphospholipid antibodies: evidence for a novel effect for an old antimalarial drug.

PubMed

Rand, Jacob H; Wu, Xiao-Xuan; Quinn, Anthony S; Ashton, Anthony W; Chen, Pojen P; Hathcock, James J; Andree, Harry A M; Taatjes, Douglas J

2010-03-18

Annexin A5 (AnxA5) is a potent anticoagulant protein that crystallizes over phospholipid bilayers (PLBs), blocking their availability for coagulation reactions. Antiphospholipid antibodies disrupt AnxA5 binding, thereby accelerating coagulation reactions. This disruption may contribute to thrombosis and miscarriages in the antiphospholipid syndrome (APS). We investigated whether the antimalarial drug, hydroxychloroquine (HCQ), might affect this prothrombotic mechanism. Binding of AnxA5 to PLBs was measured with labeled AnxA5 and also imaged with atomic force microscopy. Immunoglobulin G levels, AnxA5, and plasma coagulation times were measured on cultured human umbilical vein endothelial cells and a syncytialized trophoblast cell line. AnxA5 anticoagulant activities of APS patient plasmas were also determined. HCQ reversed the effect of antiphospholipid antibodies on AnxA5 and restored AnxA5 binding to PLBs, an effect corroborated by atomic force microscopy. Similar reversals of antiphospholipid-induced abnormalities were measured on the surfaces of human umbilical vein endothelial cells and syncytialized trophoblast cell lines, wherein HCQ reduced the binding of antiphospholipid antibodies, increased cell-surface AnxA5 concentrations, and prolonged plasma coagulation to control levels. In addition, HCQ increased the AnxA5 anticoagulant activities of APS patient plasmas. In conclusion, HCQ reversed antiphospholipid-mediated disruptions of AnxA5 on PLBs and cultured cells, and in APS patient plasmas. These results support the concept of novel therapeutic approaches that address specific APS disease mechanisms.

Functional Analysis of a Novel Genome-Wide Association Study Signal in SMAD3 That Confers Protection From Coronary Artery Disease.

PubMed

Turner, Adam W; Martinuk, Amy; Silva, Anada; Lau, Paulina; Nikpay, Majid; Eriksson, Per; Folkersen, Lasse; Perisic, Ljubica; Hedin, Ulf; Soubeyrand, Sebastien; McPherson, Ruth

2016-05-01

A recent genome-wide association study meta-analysis identified an intronic single nucleotide polymorphism in SMAD3, rs56062135C>T, the minor allele (T) which associates with protection from coronary artery disease. Relevant to atherosclerosis, SMAD3 is a key contributor to transforming growth factor-β pathway signaling. Here, we seek to identify ≥1 causal coronary artery disease-associated single nucleotide polymorphisms at the SMAD3 locus and characterize mechanisms whereby the risk allele(s) contribute to coronary artery disease risk. By genetic and epigenetic fine mapping, we identified a candidate causal single nucleotide polymorphism rs17293632C>T (D', 0.97; r(2), 0.94 with rs56062135) in intron 1 of SMAD3 with predicted functional effects. We show that the sequence encompassing rs17293632 acts as a strong enhancer in human arterial smooth muscle cells. The common allele (C) preserves an activator protein (AP)-1 site and enhancer function, whereas the protective (T) allele disrupts the AP-1 site and significantly reduces enhancer activity (P<0.001). Pharmacological inhibition of AP-1 activity upstream demonstrates that this allele-specific enhancer effect is AP-1 dependent (P<0.001). Chromatin immunoprecipitation experiments reveal binding of several AP-1 component proteins with preferential binding to the (C) allele. We show that rs17293632 is an expression quantitative trait locus for SMAD3 in blood and atherosclerotic plaque with reduced expression of SMAD3 in carriers of the protective allele. Finally, siRNA knockdown of SMAD3 in human arterial smooth muscle cells increases cell viability, consistent with an antiproliferative role. The coronary artery disease-associated rs17293632C>T single nucleotide polymorphism represents a novel functional cis-acting element at the SMAD3 locus. The protective (T) allele of rs17293632 disrupts a consensus AP-1 binding site in a SMAD3 intron 1 enhancer, reduces enhancer activity and SMAD3 expression, altering human arterial smooth muscle cell proliferation. © 2016 American Heart Association, Inc.

The Vision of Geography Underlying the Australian Geography Curriculum

ERIC Educational Resources Information Center

Maude, Alaric

2013-01-01

A common geography curriculum for Australian schools was approved in May 2013. This paper describes the conceptual and philosophical foundations of the curriculum through a discussion of its definition of geography, selection of concepts, integration of skills into the process of inquiry, and specification of learning about countries and…

Using Technology for Geography Teacher Education: Web-Based Professional Development

ERIC Educational Resources Information Center

Frazier, Cheryl A.; Boehm, Richard G.

2012-01-01

This qualitative study explores the perceived value of a video-based online workshop in Geography, "Watershed Management," part of the Geography: Teaching with the Stars series, a 22 program professional development series for teachers of geography, social studies, and environmental science. Results indicated that teachers reported…

Values in Geography.

ERIC Educational Resources Information Center

Buttimer, Annette

This resource paper on values in geography is one of several developed by the Commission on College Geography as expository documents for the use of both the student and instructor at the college level. They are designed to supplement existing texts and to fill a gap between significant research in geography and readily accessible materials. The…

On Teaching the History and Philosophy of Geography.

ERIC Educational Resources Information Center

Meir, Avinoam

To shed light on the question of whether college geography students should be and/or are being instructed about the history and philosophy of geography, a survey was undertaken to determine the educational objectives and practices of geography educators. Approximately 215 American and Canadian geographic educators and chairpersons of geography…

Geographical Teaching in Israel: A Retrospective View.

ERIC Educational Resources Information Center

Bar-Gal, Yoram

1993-01-01

Reviews geography instruction in Israel (Palestine) during past century beginning with end of Ottoman Empire to 1993 and concentrating on period since beginning of Israeli nation in 1949. Contends local and regional geography was emphasized rather than universal and systematic geography. Concludes geography is viewed as important part of national…

A Modern City--Its Geography.

ERIC Educational Resources Information Center

Mayer, Harold M.; And Others

This publication contains nine articles intended to enhance teachers' understanding of urban geography. The articles are reprinted from issues of the 1969 volume of the Journal of Geography. Urban studies has been one of the most rapidly developing fields of geography during the post World War II generation. There has been extensive research and…

The All-Russian Geography Olympiad

ERIC Educational Resources Information Center

Naumov, Alexey

2007-01-01

The history of intellectual geography competitions for secondary school students in Russia (by that time--USSR) began after World War II, when the Faculty of Geography of Lomonosov Moscow State University started to organise a yearly Geography Olympiad for Muscovite youngsters. Soon, organisers of this Olympiad decided to open it for secondary…

Oil and the economic geography of the Middle East and North Africa

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

Kortepeter, C.M.

1990-01-01

This book gives us the opportunity to follow the development of the field of economic geography as applied to the Middle East during the past half century. The materials are arranged under the following three headings: Geography and Petroleum: Boundaries and Boundary Disputes: and Social Geography.

The Lack of Interdisciplinarity in Undergraduate Geography Teaching in Turkey

ERIC Educational Resources Information Center

Bilgili, Münür

2018-01-01

The aim of this study is to understand and explore interdisciplinarity in geography and undergraduate geography courses in geography teaching departments in Turkey. There is a growing literature in science underscoring the importance of interdisciplinary approach and its beneficial outcomes. Increasing body of knowledge on social theory, on…

Aesthetics in Geography: Ideas for Teaching Geography Using Poetry

ERIC Educational Resources Information Center

Kirman, Joseph M.

2007-01-01

This article discusses how poetry can be used for teaching geography. The rational for using and writing poetry, its relationship to the National Standards for Geography, grade levels, pedagogical concerns associated with poetry writing, and subject integration are discussed. There are also classroom activities, sample discussion questions, lesson…

Human kidney anion exchanger 1 interacts with adaptor-related protein complex 1 {mu}1A (AP-1 mu1A)

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

Sawasdee, Nunghathai; Junking, Mutita; Ngaojanlar, Piengpaga

Research highlights: {yields} Trafficking defect of kAE1 is a cause of dRTA but trafficking pathway of kAE1 has not been clearly described. {yields} Adaptor-related protein complex 1 {mu}1A (AP-1 mu1A) was firstly reported to interact with kAE1. {yields} The interacting site for AP-1 mu1A on Ct-kAE1 was found to be Y904DEV907, a subset of YXXO motif. {yields} AP-1 mu1A knockdown showed a marked reduction of kAE1 on the cell membrane and its accumulation in endoplasmic reticulum. {yields} AP-1 mu1A has a critical role in kAE1 trafficking to the plasma membrane. -- Abstract: Kidney anion exchanger 1 (kAE1) mediates chloride (Cl{supmore » -}) and bicarbonate (HCO{sub 3}{sup -}) exchange at the basolateral membrane of kidney {alpha}-intercalated cells. Impaired trafficking of kAE1 leads to defect of the Cl{sup -}/HCO{sub 3}{sup -} exchange at the basolateral membrane and failure of proton (H{sup +}) secretion at the apical membrane, causing a kidney disease - distal renal tubular acidosis (dRTA). To gain a better insight into kAE1 trafficking, we searched for proteins physically interacting with the C-terminal region of kAE1 (Ct-kAE1), which contains motifs crucial for intracellular trafficking, by a yeast two-hybrid (Y2H) system. An adaptor-related protein complex 1 {mu}1A (AP-1 mu1A) subunit was found to interact with Ct-kAE1. The interaction between either Ct-kAE1 or full-length kAE1 and AP-1 mu1A were confirmed in human embryonic kidney (HEK) 293T by co-immunoprecipitation, affinity co-purification, co-localization, yellow fluorescent protein (YFP)-based protein fragment complementation assay (PCA) and GST pull-down assay. The interacting site for AP-1 mu1A on Ct-kAE1 was found to be Y904DEV907, a subset of YXXO motif. Interestingly, suppression of endogenous AP-1 mu1A in HEK 293T by small interfering RNA (siRNA) decreased membrane localization of kAE1 and increased its intracellular accumulation, suggesting for the first time that AP-1 mu1A is involved in the kAE1 trafficking of kidney {alpha}-intercalated cells.« less

[Fluid therapy in acute pancreatitis].

PubMed

de-Madaria, Enrique

2013-12-01

Severe acute pancreatitis (AP) is associated with an increased need for fluids due to fluid sequestration and, in the most severe cases, with decreased peripheral vascular tone. For several decades, clinical practice guidelines have recommended aggressive fluid therapy to improve the prognosis of AP. This recommendation is based on theoretical models, animal studies, and retrospective studies in humans. Recent studies suggest that aggressive fluid administration in all patients with AP could have a neutral or harmful effect. Fluid therapy based on Ringer's lactate could improve the course of the disease, although further studies are needed to confirm this possibility. Most patients with AP do not require invasive monitoring of hemodynamic parameters to guide fluid therapy administration. Moreover, the ability of these parameters to improve prognosis has not been demonstrated. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Beyond Knee-Jerk Environmental Thinking: Teaching Geographic Perspectives on Conservation, Preservation and the Hetch Hetchy Valley Controversy

ERIC Educational Resources Information Center

Moseley, William G.

2009-01-01

Attention to scale, use of space and connections between places and regions are general, yet distinctive, geographical concepts that may be employed in introductory level human-environment geography courses to distinguish them from other environmental studies offerings. This article demonstrates how attention to the aforementioned concepts…

Spaces of Spiritual Citizenship: Children's Relational and Emotional Encounters with the Everyday School Environment

ERIC Educational Resources Information Center

Hemming, Peter J.

2013-01-01

This article addresses the issue of children's spiritual, relational and emotional encounters with the primary school environment, with reference to concepts and theories from both education studies and human geography. Drawing on mixed-method qualitative research in two case study institutions, the article examines pupils' photographed "special…

The Impacts of Highway Expansion on Population Change: An Integrated Spatial Approach

ERIC Educational Resources Information Center

Chi, Guangqing

2010-01-01

The effects of highways on transforming human society and promoting population change have been investigated in several disciplines, including geography, sociology, economics, and planning. Currently, the primary highway construction activity in the nation is highway expansion; however, this expansion has not been the focus of much of the existing…

Challenging Ideals of Reciprocity in Undergraduate Teaching: The Unexpected Benefits of Unpredictable Cross-Cultural Fieldwork

ERIC Educational Resources Information Center

Hammersley, Laura A.; Bilous, Rebecca H.; James, Sarah W.; Trau, Adam M.; Suchet-Pearson, Sandie

2014-01-01

Geographers are increasingly grappling with the theoretical and practical implications of integrating an ethics of reciprocity into undergraduate learning and teaching. This paper draws on the unexpected experiences of a third-year human geography research methods fieldtrip to examine the process of balancing undergraduate student learning and…

I.D.G. Bulletin 1979/80.

ERIC Educational Resources Information Center

Meijer, Henk, Comp.

This document focuses on the history and organization of physical planning in the Netherlands. It is part of a series of bulletins on the human and physical geography of the Netherlands. Information, presented in expository, tabular, photographic, and cartographic form, is arranged in four major sections. Section I, which contains the bulk of the…

Job Market Looks Brighter for Some Ph.D.'s

ERIC Educational Resources Information Center

June, Audrey Williams

2012-01-01

The author reports on the academic job market that is showing signs of turning around after a multiyear slump. Job-outlook data released by professional associations in recent months show an uptick in the number of jobs available in several fields, including history, the humanities and foreign languages, sociology, geography, and political…

Innovative Ways to Look at New World Historical Geography

ERIC Educational Resources Information Center

Raat, W. Dirk

2004-01-01

The Cape Canaveral endeavor led the author to contemplate the history of cartography and the role of geographers and historians in describing the human-environment nexus. He was especially interested in the depiction of the Americas by world historians and geographers. He wanted to answer the question, "How do world historians and geographers…

World History and Geography: Ancient Civilizations. Course Models for the History-Social Science Framework: Grade 6.

ERIC Educational Resources Information Center

Hanson, Ralph, Ed.; Brooks, Diane

This document outlines ancient civilization teaching models for California sixth graders. It is another response to teachers' requests for practical assistance in implementing the "History-Social Science Framework." Units include: (1) Early Humankind and the Development of Human Societies; (2) The Beginnings of Civilization in the Near…

Scale in Education Research: Towards a Multi-Scale Methodology

ERIC Educational Resources Information Center

Noyes, Andrew

2013-01-01

This article explores some theoretical and methodological problems concerned with scale in education research through a critique of a recent mixed-method project. The project was framed by scale metaphors drawn from the physical and earth sciences and I consider how recent thinking around scale, for example, in ecosystems and human geography might…

Storytelling: The Heart and Soul of Education. PREL Briefing Paper.

ERIC Educational Resources Information Center

Koki, Stan

This briefing paper presents research on the importance of storytelling in human experience and explores the relevance of storytelling as an instructional tool in Pacific classrooms. The paper provides teachers with suggestions for getting started with storytelling in the classroom, such as: (1) introduce units about geography and people of the…

The Corporeal Marker Project (CMP): Teaching about Bodily Difference, Identity and Place through Experience

ERIC Educational Resources Information Center

Fluri, Jennifer L.; Trauger, Amy

2011-01-01

In response to recent articles and ideas for experiential learning activities in human geography, this paper outlines a particular approach to learning about the body, difference, mobility and geographic space through experience. The Corporeal Marker Project designed and implemented by the authors provides a spatial experience of difference for…

"Doing Gender" at "Body Worlds": Embodying Field Trips as Affective Educational Experience

ERIC Educational Resources Information Center

Davidson, Joyce; Huff, Leah; Bridgen, Jen; Carolan, Andrea; Chang, Ashley; Ennis, Katherine; Loynes, Kathryn; Miller, Jen

2009-01-01

This paper discusses the background, experience and outcomes of an explicitly feminist field trip to Gunther von Hagen's "Body Worlds 2: The Anatomical Exhibition of Real Human Bodies". The cultural landscape of this exhibition materialized gendered geographies very powerfully, facilitating observation and analysis of embodied and emotional,…

Changing the World around Them: A Letter from Turkiye's Harran Plain.

ERIC Educational Resources Information Center

Swartz, Avonna Kessler

1992-01-01

Describes a doctoral student's experiences on a trip to Turkey. Discusses the Southeast Anatolia Project involving dam building on the headwaters of the Euphrates to provide electricity and irrigation. Suggests the experience as an example demonstration of complexities of human and environmental interaction and other themes of geography. (DK)

Gemfibrozil, a Lipid-lowering Drug, Inhibits the Induction of Nitric-oxide Synthase in Human Astrocytes*

PubMed Central

Pahan, Kalipada; Jana, Malabendu; Liu, Xiaojuan; Taylor, Bradley S.; Wood, Charles; Fischer, Susan M.

2007-01-01

Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astrocytes. Similar to gemfibrozil, clofibrate, another fibrate drug, also inhibited the expression of iNOS. Inhibition of human iNOS promoter-driven luciferase activity by gemfibrozil in cytokine-stimulated U373MG astroglial cells suggests that this compound inhibits the transcription of iNOS. Since gemfibrozil is known to activate peroxisome proliferator-activated receptor-α (PPAR-α), we investigated the role of PPAR-α in gemfibrozil-mediated inhibition of iNOS. Gemfibrozil induced peroxisome proliferator-responsive element (PPRE)-dependent luciferase activity, which was inhibited by the expression of ΔhPPAR-α, the dominant-negative mutant of human PPAR-α. However, ΔhPPAR-α was unable to abrogate gemfibrozil-mediated inhibition of iNOS suggesting that gemfibrozil inhibits iNOS independent of PPAR-α. The human iNOS promoter contains consensus sequences for the binding of transcription factors, including interferon-γ (IFN-γ) regulatory factor-1 (IRF-1) binding to interferon-stimulated responsive element (ISRE), signal transducer and activator of transcription (STAT) binding to γ-activation site (GAS), nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and CCAAT/enhancer-binding protein β (C/EBPβ); therefore, we investigated the effect of gemfibrozil on the activation of these transcription factors. The combination of interleukin (IL)-1β and IFN-γ induced the activation of NF-κB, AP-1, C/EBPβ, and GAS but not that of ISRE, suggesting that IRF-1 may not be involved in cytokine-induced expression of iNOS in human astrocytes. Interestingly, gemfibrozil strongly inhibited the activation of NF-κB, AP-1, and C/EBPβ but not that of GAS in cytokine-stimulated astroglial cells. These results suggest that gemfibrozil inhibits the induction of iNOS probably by inhibiting the activation of NF-κB, AP-1, and C/EBPβ and that gemfibrozil, a prescribed drug for humans, may further find its therapeutic use in neuroinflammatory diseases. PMID:12244038

Macroecological factors shape local-scale spatial patterns in agriculturalist settlements.

PubMed

Tao, Tingting; Abades, Sebastián; Teng, Shuqing; Huang, Zheng Y X; Reino, Luís; Chen, Bin J W; Zhang, Yong; Xu, Chi; Svenning, Jens-Christian

2017-11-15

Macro-scale patterns of human systems ranging from population distribution to linguistic diversity have attracted recent attention, giving rise to the suggestion that macroecological rules shape the assembly of human societies. However, in which aspects the geography of our own species is shaped by macroecological factors remains poorly understood. Here, we provide a first demonstration that macroecological factors shape strong local-scale spatial patterns in human settlement systems, through an analysis of spatial patterns in agriculturalist settlements in eastern mainland China based on high-resolution Google Earth images. We used spatial point pattern analysis to show that settlement spatial patterns are characterized by over-dispersion at fine spatial scales (0.05-1.4 km), consistent with territory segregation, and clumping at coarser spatial scales beyond the over-dispersion signals, indicating territorial clustering. Statistical modelling shows that, at macroscales, potential evapotranspiration and topographic heterogeneity have negative effects on territory size, but positive effects on territorial clustering. These relationships are in line with predictions from territory theory for hunter-gatherers as well as for many animal species. Our results help to disentangle the complex interactions between intrinsic spatial processes in agriculturalist societies and external forcing by macroecological factors. While one may speculate that humans can escape ecological constraints because of unique abilities for environmental modification and globalized resource transportation, our work highlights that universal macroecological principles still shape the geography of current human agricultural societies. © 2017 The Author(s).

HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail

PubMed Central

Roeth, Jeremiah F.; Williams, Maya; Kasper, Matthew R.; Filzen, Tracey M.; Collins, Kathleen L.

2004-01-01

To avoid immune recognition by cytotoxic T lymphocytes (CTLs), human immunodeficiency virus (HIV)-1 Nef disrupts the transport of major histocompatibility complex class I molecules (MHC-I) to the cell surface in HIV-infected T cells. However, the mechanism by which Nef does this is unknown. We report that Nef disrupts MHC-I trafficking by rerouting newly synthesized MHC-I from the trans-Golgi network (TGN) to lysosomal compartments for degradation. The ability of Nef to target MHC-I from the TGN to lysosomes is dependent on expression of the μ1 subunit of adaptor protein (AP) AP-1A, a cellular protein complex implicated in TGN to endolysosomal pathways. We demonstrate that in HIV-infected primary T cells, Nef promotes a physical interaction between endogenous AP-1 and MHC-I. Moreover, we present data that this interaction uses a novel AP-1 binding site that requires amino acids in the MHC-I cytoplasmic tail. In sum, our evidence suggests that binding of AP-1 to the Nef–MHC-I complex is an important step required for inhibition of antigen presentation by HIV. PMID:15569716

Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo

PubMed Central

Yang, Jing-Jing; Li, Peng; Wang, Fu; Liang, Wen-Jing; Ma, Hui; Chen, Yuan; Ma, Zhi-Min; Li, Quan-Zhong; Peng, Qi-Sheng; Zhang, Yun; Wang, Shuang-Xi

2016-01-01

Aims Aspirin has been used for the secondary prevention and treatment of cardiovascular disease for several decades. We investigated the roles of transcriptional factor activator protein 2α (AP-2α) in the beneficial effects of aspirin in the growth and vulnerability of atherosclerotic plaque. Methods and Results In mice deficient of apolipoprotein E (Apoe-/-), aspirin (20, 50 mg/kg/day) suppressed the progression of atherosclerosis in aortic roots and increased the plaque stability in carotid atherosclerotic plaques induced by collar-placement. In vivo lentivirus-mediated RNA interference of AP-2α reversed the inhibitory effects of aspirin on atherosclerosis in Apoe-/- mice. Mechanically, aspirin increased AP-2α phosphorylation and its activity, upregulated IkBα mRNA and protein levels, and reduced oxidative stress in cultured vascular smooth muscle cells. Furthermore, deficiency of AP-2α completely abolished aspirin-induced upregulation of IkBα levels and inhibition of oxidative stress in Apoe-/- mice. Clinically, conventional doses of aspirin increased AP-2α phosphorylation and IkBα protein expression in humans subjects. Conclusion Aspirin activates AP-2α to upregulate IkBα gene expression, resulting in attenuations of plaque development and instability in atherosclerosis. PMID:27391154

Population structure, migration, and diversifying selection in the Netherlands

PubMed Central

Abdellaoui, Abdel; Hottenga, Jouke-Jan; Knijff, Peter de; Nivard, Michel G; Xiao, Xiangjun; Scheet, Paul; Brooks, Andrew; Ehli, Erik A; Hu, Yueshan; Davies, Gareth E; Hudziak, James J; Sullivan, Patrick F; van Beijsterveldt, Toos; Willemsen, Gonneke; de Geus, Eco J; Penninx, Brenda W J H; Boomsma, Dorret I

2013-01-01

Genetic variation in a population can be summarized through principal component analysis (PCA) on genome-wide data. PCs derived from such analyses are valuable for genetic association studies, where they can correct for population stratification. We investigated how to capture the genetic population structure in a well-characterized sample from the Netherlands and in a worldwide data set and examined whether (1) removing long-range linkage disequilibrium (LD) regions and LD-based SNP pruning significantly improves correlations between PCs and geography and (2) whether genetic differentiation may have been influenced by migration and/or selection. In the Netherlands, three PCs showed significant correlations with geography, distinguishing between: (1) North and South; (2) East and West; and (3) the middle-band and the rest of the country. The third PC only emerged with minimized LD, which also significantly increased correlations with geography for the other two PCs. In addition to geography, the Dutch North–South PC showed correlations with genome-wide homozygosity (r=0.245), which may reflect a serial-founder effect due to northwards migration, and also with height (♂: r=0.142, ♀: r=0.153). The divergence between subpopulations identified by PCs is partly driven by selection pressures. The first three PCs showed significant signals for diversifying selection (545 SNPs - the majority within 184 genes). The strongest signal was observed between North and South for the functional SNP in HERC2 that determines human blue/brown eye color. Thus, this study demonstrates how to increase ancestry signals in a relatively homogeneous population and how those signals can reveal evolutionary history. PMID:23531865

Teachers Envisioning Future Geography Education at Their Schools

ERIC Educational Resources Information Center

Béneker, Tine; Palings, Hans; Krause, Uwe

2015-01-01

One of the challenges of a geography teacher education program is preparing teachers for their leading roles in keeping geography education relevant for the young people of today. It is important to allow teachers to think about geography education and the future and to foster their curriculum-making competences. In a master course at Fontys…

Designs, Techniques, and Reporting Strategies in Geography Education: A Review of Research Methods

ERIC Educational Resources Information Center

Zadrozny, Joann; McClure, Caroline; Lee, Jinhee; Jo, Injeong

2016-01-01

A wide variety of research is being completed and published in geography education. The purpose of this article is to provide a general overview of the different types of methodologies, research designs, and techniques used by geography education researchers. Analyzing three geography education journals, we found 191 research articles published…

Integrating Opportunities: Applied Interdisciplinary Research in Undergraduate Geography and Geology Education

ERIC Educational Resources Information Center

Kubiatko, Milan; Mrazkova, Katerina; Janko, Tomas

2012-01-01

Pupils' perception of any science subject significantly influences their achievement. Identification of perception of some subject is essential part of educational research. This study is focused on finding out differences in the four dimensions of geography perception (1. Geography as a school subject; 2. Geography and environment; 3 Importance…

Geography of Religion at Slippery Rock State College.

ERIC Educational Resources Information Center

Hannon, Thomas J., Jr.

The paper presents a course outline intended for use in a one semester geography of religion course on the college level. Geography of religion is interpreted to include all aspects of the impact of religion on cultural, political, and economic geography. Objectives are to emphasize distributional aspects of religion and religious phenomena,…

Is Singapore's School Geography Relevant to Our Changing World?

ERIC Educational Resources Information Center

Chang, Chew-Hung

2011-01-01

How school geography should be taught has been a longstanding issue for geography educators. In some countries, state or national level curriculum predicates how the subject should be taught in schools. This paper examines these questions in relation to existing frameworks of conceptualizing school geography, such as the International Charter on…

What Is Geography? Perceptions of First Year Undergraduates in South Africa

ERIC Educational Resources Information Center

Knight, Jasper; Robinson, Kirsten

2017-01-01

Disciplines such as Geography are well placed to respond to the changing needs of society and the effective application of geographical knowledge to real-world problems. This project surveyed first year Geography undergraduates' understanding of "What is Geography?", both before and after an exercise in which geographic topics were…

Interactive Problem-Solving Geography: An Introduction in Chinese Classrooms to Locational Analysis

ERIC Educational Resources Information Center

Wai, Nu Nu; Giles, John H.

2006-01-01

Reform in geography education, as reflected in "Geography for Life: National Geography Standards" (1994) for the U.S.A., favors a constructivist approach to learning. This study examines the acceptance of this approach among students in two upper secondary schools in China. A lesson was developed to illustrate interactive problem solving…

Rethinking Postgraduate Geography Education in the USA: Issues and Concerns

ERIC Educational Resources Information Center

Foote, Kenneth; Bednarz, Sarah; Monk, Janice; Solem, Michael; Stoltman, Joseph

2012-01-01

Postgraduate geography education in the USA is growing and changing. In recent years, the number of postgraduate programs has increased at both the doctoral and master's levels. Interest in improving and reforming doctoral education has increased dramatically both inside and outside geography, and geography has been involved in these reforms.…

Quality Rankings of Ph.D.-Granting Departments of Geography, 1925-1980.

ERIC Educational Resources Information Center

Warf, Barney; Webster, David S.

All of the major academic quality rankings of American Ph.D.-granting geography departments during 1925-80 are examined, and trends in the universities and regions in which the best Ph.D.-granting geography departments have been located are analyzed. Seven major ratings of geography departments are considered. Reputational rankings were conducted…

Finding a Way: Learning Activities in Geography for Grades 7-11.

ERIC Educational Resources Information Center

National Council for Geographic Education.

This set of curriculum modules contains geography learning activities that emphasize strategies to encourage young women in geography and social studies classes. Compiled in an effort to improve the motivation and achievement levels of students in geography classrooms, grades 7-11, the modules aim to boost academic performance and overall interest…

Fieldwork in Geography Education: Defining or Declining? The State of Fieldwork in Canadian Undergraduate Geography Programs

ERIC Educational Resources Information Center

Wilson, Heather; Leydon, Joseph; Wincentak, Joanna

2017-01-01

This paper investigates the prevalence of fieldwork in undergraduate Geography programs in Canada. It examines the presence of fieldwork, provided through both field courses and courses that include fieldwork components, by reviewing program requirements and course offerings in undergraduate geography programs. The research explores the extent to…

Primary Geography in the Republic of Ireland: Practices, Issues and Possible Futures

ERIC Educational Resources Information Center

Pike, Susan

2015-01-01

In the Republic of Ireland, geography is recognized as an important subject for children to learn and all pupils take it throughout their primary school years. The current curriculum, the Primary School Curriculum-Geography, follows a tradition of innovative, child-centered geography curricula in Ireland. This article outlines the history of…

The Geography Teacher. Volume 5, Number 2, 2008

ERIC Educational Resources Information Center

Geography Teacher, 2008

2008-01-01

"The Geography Teacher" provides hands-on reference and educative material for K-12 Geography teachers. The journal also pioneers innovative ideas for contemporary teaching methods, including lesson plans. This issue contains the following: (1) Ask Dr. de Blij (Harm de Blij); (2) Geography: Is it a Boy's Subject? (Lisa Smitreski); (3) A…

UHPLC-(ESI)QTOF MS/MS profiling of quercetin metabolites in human plasma postconsumption of applesauce enriched with apple peel and onion.

PubMed

Lee, Jihyun; Ebeler, Susan E; Zweigenbaum, Jerry A; Mitchell, Alyson E

2012-08-29

An ultrahigh pressure liquid chromatography accurate mass quadrupole time-of-flight mass spectrometry with electrospray ionization (UHPLC-(ESI)QTOF MS/MS) method was developed for measuring individual quercetin metabolites in human plasma with high sensitivity and high selectivity. Quercetin (3,3',4',5,7-pentahydroxyflavone) occurs as glycosides in foods. The composition of glycosides is species and cultivar specific. In humans, quercetin undergoes extensive biotransformation, resulting in a range of metabolites. The bioactivity of quercetin metabolites will depend on the type and position of the conjugates. Herein, individual quercetin metabolites (i.e., sulfate, glucuronide or methyl conjugates) were identified by accurate mass MS in human plasma (females = 8 and males = 8) over 24 h after consumption of applesauce enriched with either micronized apple peel (AP) or onion powder (OP). The AP and OP contained ~180 μmol of quercetin glycosides. The relative amounts of quercetin metabolites were quantified in plasma. The complement of identified quercetin metabolites was similar after consumption of AP and OP. Primary metabolites included the following: quercetin sulfate, quercetin glucuronide, and quercetin diglucuronide. A quercetin glutathione adduct was identified in negative ion mode but not apparent in positive ion mode. The pharmacokinetic parameters for AUC0-24 h and Cmax were significantly different for AP and OP. For example, consumption of the AP resulted in Cmax of quercetin sulfate, 4.6 ng/mL; quercetin glucuronide, 15.5 ng/mL; quercetin diglucuronide, 9.3 ng/mL; quercetin glucuronide sulfate, 1.3 ng/mL; methyl quercetin glucuronide, 7.5 ng/mL; and methyl quercetin diglucuronide, 3.6 ng/mL, whereas the OP resulted in Cmax of quercetin sulfate, 37.3 ng/mL; quercetin glucuronide, 212.8 ng/mL; quercetin diglucuronide, 168.8 ng/mL; quercetin glucuronide sulfate, 43.0 ng/mL; methyl quercetin glucuronide, 90.1 ng/mL; methyl quercetin diglucuronide, 65.4 ng/mL. Gender-related differences in the AUC0-24 h for quercetin sulfate and quercetin sulfate glucuronide metabolites were also observed.

Hydrocortisone at stress-associated concentrations helps maintain human heart rate variability during subsequent endotoxin challenge.

PubMed

Rassias, Athos J; Guyre, Paul M; Yeager, Mark P

2011-12-01

We evaluated the differential impact of stress-associated vs high pharmacologic concentrations of hydrocortisone pretreatment on heart rate variability (HRV) during a subsequent systemic inflammatory stimulus. Healthy volunteers were randomized to receive placebo (Control) and hydrocortisone at 1.5 μg/kg per minute (STRESS) or at 3.0 μg/kg per minute (PHARM) as a 6-hour infusion. The STRESS dose was chosen to replicate the condition of physiologic adrenal cortical output during acute systemic stress. The PHARM dose was chosen to induce a supraphysiologic concentration of cortisol. The next day, all subjects received 2 ng/kg Escherichia coli endotoxin (lipopolysaccharide). Heart rate variability was analyzed with the statistic approximate entropy (ApEn). A lower ApEn correlates with decreased HRV. At the 3-hour nadir, the decrease in ApEn in the STRESS group was significantly less compared to placebo (P < .03), whereas ApEn in the PHARM group was not statistically different. We also found that the maximal decrease in ApEn preceded maximal increase in heart rate in all groups. The decrease in R-R interval was maximal at 4 hours, whereas the ApEn nadir was 1 hour earlier at 3 hours. Pretreatment with a stress dose of hydrocortisone but not a higher pharmacologic dose maintained a significantly higher ApEn after endotoxin exposure when compared to a placebo. In addition, decreases in ApEn preceded increases in heart rate. Copyright © 2011 Elsevier Inc. All rights reserved.

HIV-1 Nef-induced Down-Regulation of MHC Class I Requires AP-1 and Clathrin but Not PACS-1 and Is Impeded by AP-2

PubMed Central

Lubben, Nienke B.; Sahlender, Daniela A.; Motley, Alison M.; Lehner, Paul J.; Benaroch, Philippe

2007-01-01

Major histocompatibility complex class I is down-regulated from the surface of human immunodeficiency virus (HIV)-1-infected cells by Nef, a virally encoded protein that is thought to reroute MHC-I to the trans-Golgi network (TGN) in a phosphofurin acidic cluster sorting protein (PACS) 1, adaptor protein (AP)-1, and clathrin-dependent manner. More recently, an alternative model has been proposed, in which Nef uses AP-1 to direct MHC-I to endosomes and lysosomes. Here, we show that knocking down either AP-1 or clathrin with small interfering RNA inhibits the down-regulation of HLA-A2 (an MHC-I isotype) by Nef in HeLa cells. However, knocking down PACS-1 has no effect, not only on Nef-induced down-regulation of HLA-A2 but also on the localization of other proteins containing acidic cluster motifs. Surprisingly, knocking down AP-2 actually enhances Nef activity. Immuno-electron microscopy labeling of Nef-expressing cells indicates that HLA-A2 is rerouted not to the TGN, but to endosomes. In AP-2–depleted cells, more of the HLA-A2 localizes to the inner vesicles of multivesicular bodies. We propose that depleting AP-2 potentiates Nef activity by altering the membrane composition and dynamics of endosomes and causing increased delivery of HLA-A2 to a prelysosomal compartment. PMID:17581864

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

Koenig, Xaver; Kovar, Michael; Rubi, Lena

The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart's electrophysiology. Here, to assess the drug's cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologouslymore » expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Na{sub v}1.5 sodium and Ca{sub v}1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (≥ 10 μM) even shortened the AP. These findings can be explained by the drug's calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine's inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. - Highlights: • We study effects of anti-addiction drug ibogaine on ionic currents in cardiomyocytes. • We assess the cardiac ion channel profile of ibogaine. • Ibogaine inhibits hERG potassium, sodium and calcium channels. • Ibogaine’s effects on ion channels are a potential source of cardiac arrhythmias. • 18-Methoxycoronaridine has a lower affinity for cardiac ion channels than ibogaine.« less

Connectivity as a multiple: In, with and as "nature".

PubMed

Hodgetts, Timothy

2018-03-01

Connectivity is a central concept in contemporary geographies of nature, but the concept is often understood and utilised in plural ways. This is problematic because of the separation, rather than the confusion, of these different approaches. While the various understandings of connectivity are rarely considered as working together, the connections between them have significant implications. This paper thus proposes re-thinking connectivity as a "multiple". It develops a taxonomy of existing connectivity concepts from the fields of biogeography and landscape ecology, conservation biology, socio-economic systems theory, political ecology and more-than-human geography. It then considers how these various understandings might be re-thought not as separate concerns, but (following Annemarie Mol) as "more than one, but less than many". The implications of using the connectivity multiple as an analytic for understanding conservation practices are demonstrated through considering the creation of wildlife corridors in conservation practice. The multiple does not just serve to highlight the practical and theoretical linkages between ecological theories, social inequities and affectual relationships in more-than-human worlds. It is also suggestive of a normative approach to environmental management that does not give temporal priority to biological theories, but considers these as always already situated in these social, often unequal, always more-than-human ecologies.

Biotransformation of 1-nitropyrene to 1-aminopyrene and N-formyl-1-aminopyrene by the human intestinal microbiota

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

Manning, B.W.; Cerniglia, C.E.; Federle, T.W.

The nitropolycyclic aromatic hydrocarbon 1-nitropyrene (1-NP) is an environmental pollutant, a potent bacterial and mammalian mutagen, and a carcinogen. The metabolism of 1-NP by the human intestinal microbiota was studied using a semicontinuous culture system that simulates the colonic lumen. (/sup 3/H)-1-Nitropyrene was metabolized by the intestinal microbiota to 1-aminopyrene (1-AP) and N-formyl-1-aminopyrene (FAP) as determined by high-performance liquid chromatography (HPLC) and mass spectrometry. Twenty-four hours after the addition of (/sup 3/H)-1-NP, the formylated compound and 1-AP accounted for 20 and 80% of the total metabolism respectively. This percentage increased to 66% for FAP after 24 h following 10 dmore » of chronic exposure to unlabeled 1-NP, suggesting metabolic adaptation to 1-NP by the microbiota. Both 1-AP and FAP have been shown to be nonmutagenic towards Salmonella typhimurium TA98, which indicates that the intestinal microflora may potentially detoxify 1-NP.« less

The synergistic transactivation of the hepatitis B viral (HBV) pregenomic promoter by the E6 protein of human papillomavirus type 16 (HPV-16 E6) with HBV X protein was mediated through the AP1 site of E element in the enhancer I (EnI) in human liver cell.

PubMed

Lee, D H; Choi, B H; Rho, H M

1999-11-01

Infection by HBV of a cell already infected with other viral species or vice versa has been suggested as being involved in hepatocellular carcinoma. Using the CAT assay method, we investigated the interactive roles of HBx and potentially oncogenic and transactivating viral early proteins such as Ad5 E1A, HPV-16 E6, and SV40 T ag. In the presence of HBx, only HPV-16 E6 showed significant synergistic transactivation of EnI. We further investigated the function of the HPV-16 E6 using deletion, heterologous promoter, and mutation analyses on the EnI promoter. The results showed that the synergistic effect was mediated through the AP1 site of the E element in EnI by the direct activation of AP1 and support the idea that the infection by HBV of the cell with other viral species such as HPV-16 could increase the transcription activity of the HBV and other oncogenes containing an AP1 site in the promoter. Copyright 1999 Academic Press.

Teaching American Ethnic Geography. Pathways in Geography Series Title No. 18.

ERIC Educational Resources Information Center

Estaville, Lawrence E., Ed.; Rosen, Carol J., Ed.

U.S. ethnic geography is an increasingly important focus of study due to cultural diversity and continued growth of the United States. Geographers are carefully studying the spatial aspects of present U.S. ethnic groups. This collection of essays addresses the important need for creating innovative approaches in teaching U.S. ethnic geography in…

Employing SWOT Analysis in Coursework on the Geographies of Regional Economic Development and Trade

ERIC Educational Resources Information Center

Kalafsky, Ronald V.; Sonnichsen, Tyler

2015-01-01

The use of SWOT analysis is a means through which geography students can investigate key concepts in economic geography and essential topics in regional economic development. This article discusses the results of a course project where economic geography students employed SWOT analysis to explore medium-sized metropolitan areas across the southern…

Perceptions of Geography Teachers to Integrating Technology to Teaching and Their Practices

ERIC Educational Resources Information Center

Sanli, Cennet; Sezer, Adem; Pinar, Adnan

2016-01-01

In present study the objective has been to manifest perceptions and practices of geography teachers towards integrating technology to teaching geography. In 5 different types of schools within Nevsehir (Turkey) city center, a total of 22 geography teachers volunteering to participate in the research were included in this study in which data were…

A Critical Account of What "Geography" Means to Primary Trainee Teachers in England

ERIC Educational Resources Information Center

Puttick, Steven; Paramore, John; Gee, Nick

2018-01-01

Research on trainee teachers' conceptions of geography has criticised their views for being limited, and failing to appreciate the breadth or depth of geography. A body of research in this area has developed over the past two decades, producing well-established classifications through which to analyse conceptions of geography. This contribution…

Fifteen Year Follow-Up Geography Skills Test Administered in Indiana, 1987 and 2002

ERIC Educational Resources Information Center

Bein, F. L.; Hayes, James J.; Jones, Thomas G.

2009-01-01

After fifteen years of geographic education efforts, a baseline geography skills test was repeated in Indiana. In 2002, 2,278 students in college freshman geography courses were tested with a revision of the National Council for Geographic Education Competency-Based Geography Test, Secondary Level Form II. The test measured geographic ability in…

Geography Preservice Teachers' Disposition toward Teaching Spatial Thinking through Geography: A Comparison between China and Korea

ERIC Educational Resources Information Center

Lee, Jinhee; Jo, Injeong; Xuan, Xiaowei; Zhou, Weiguo

2018-01-01

Although geography education researchers in both China and Korea acknowledge that the education of spatial thinking and the development of teachers' dispositions toward teaching spatial thinking are important, very few studies are available on the topic. This article examines the dispositions of Chinese and Korean geography preservice teachers'…

An Investigation into Geography Teachers' Use of Current Events in Geography Classes

ERIC Educational Resources Information Center

Degirmenci, Yavuz; Ilter, Ilhan

2017-01-01

This study aimed to investigate the extent to which geography teachers use current events within the context of their geography instruction, their sources of information about current events, the methods and techniques they adopt while using current events in their teaching and the skills and values they expect their students to develop. The…

Learning with and by Language: Bilingual Teaching Strategies for the Monolingual Language-Aware Geography Classroom

ERIC Educational Resources Information Center

Morawski, Michael; Budke, Alexandra

2017-01-01

Geography lessons center on a language-based product with socially relevant geographic content. The subject of geography in secondary schools in Germany faces three major challenges that make a stronger focus on language in the monolingual geography classroom necessary. First, more than 30 percent of German pupils in secondary schools have a…

An Investigation of Non-Thesis Master's Program Geography Teacher Candidates' Attitudes towards Teaching Profession regarding Several Socio-Cultural Features

ERIC Educational Resources Information Center

Sezer, Adem; Kara, Hasan; Pinar, Adnan

2011-01-01

The purpose of this study is to examine the attitudes of non-thesis master's degree program: geography teacher candidates towards teaching profession regarding several socio-cultural features. The study was conducted in different universities with 218 geography teacher candidates enrolled in the geography education non-thesis master's degree…

Transition and Transformation: The Influence of a Learning Package on Student Performance in Soils Geography Studies

ERIC Educational Resources Information Center

Korze, Ana Vovk

2005-01-01

Recent political and economic developments in Slovenia, especially its accession to the European Union in 2004, have led to a significant reappraisal of the geography curriculum in higher education, and particularly those elements dealing with the teaching of soils. Physical geography, and especially soils geography, has long been an important…

Pre-Service Teachers Learn to Teach Geography: A Suggested Course Model

ERIC Educational Resources Information Center

Mitchell, Jerry T.

2018-01-01

How to improve geography education via teacher preparation programs has been a concern for nearly three decades, but few examples of a single, comprehensive university-level course exist. The purpose of this article is to share the model of a pre-service geography education methods course. Within the course, geography content (physical and social)…

Geography Standards in the United States: Past Influences and Future Prospects

ERIC Educational Resources Information Center

Bednarz, Sarah Witham; Heffron, Susan Gallagher; Solem, Michael

2014-01-01

The purpose of this article is to examine how geography is represented and positioned in primary and secondary (referred to here as K-12) education in the United States through a critical analysis of the content and implementation of the National Geography Standards, "Geography for Life." We begin by providing context on the organization…

Defining Primary Geography from Teachers' Expertise: What Chilean Teachers Mean by Geography

ERIC Educational Resources Information Center

Salinas-Silva, Victor; Perez-Gallardo, Patricio; Arenas-Martija, Andoni

2015-01-01

This article examines teachers' subject expertise in a context where geography could be considered a neglected school subject. Using an empirical approach to the problem, the article aims to provide a view on the dynamics of teaching primary geography in Chile, through considering teachers' narratives on curriculum making and their associated…

Geography's Crosscutting Themes: Golden Anniversary Reflections on "The Four Traditions of Geography"

ERIC Educational Resources Information Center

Murphy, Alexander B.

2014-01-01

William Pattison's seminal 1964 article outlining geography's four core traditions provided an informative overview of distinct strands of research and teaching in geography. His article enhanced appreciation of the discipline's intellectual diversity, but it did not address why the identified traditions should be grouped together…

Association of papillomavirus E6 proteins with either MAML1 or E6AP clusters E6 proteins by structure, function, and evolutionary relatedness

PubMed Central

Brimer, Nicole

2017-01-01

Papillomavirus E6 proteins bind to LXXLL peptide motifs displayed on targeted cellular proteins. Alpha genus HPV E6 proteins associate with the cellular ubiquitin ligase E6AP (UBE3A), by binding to an LXXLL peptide (ELTLQELLGEE) displayed by E6AP, thereby stimulating E6AP ubiquitin ligase activity. Beta, Gamma, and Delta genera E6 proteins bind a similar LXXLL peptide (WMSDLDDLLGS) on the cellular transcriptional co-activator MAML1 and thereby repress Notch signaling. We expressed 45 different animal and human E6 proteins from diverse papillomavirus genera to ascertain the overall preference of E6 proteins for E6AP or MAML1. E6 proteins from all HPV genera except Alpha preferentially interacted with MAML1 over E6AP. Among animal papillomaviruses, E6 proteins from certain ungulate (SsPV1 from pigs) and cetacean (porpoises and dolphins) hosts functionally resembled Alpha genus HPV by binding and targeting the degradation of E6AP. Beta genus HPV E6 proteins functionally clustered with Delta, Pi, Tau, Gamma, Chi, Mu, Lambda, Iota, Dyokappa, Rho, and Dyolambda E6 proteins to bind and repress MAML1. None of the tested E6 proteins physically and functionally interacted with both MAML1 and E6AP, indicating an evolutionary split. Further, interaction of an E6 protein was insufficient to activate degradation of E6AP, indicating that E6 proteins that target E6AP co-evolved to separately acquire both binding and triggering of ubiquitin ligase activation. E6 proteins with similar biological function clustered together in phylogenetic trees and shared structural features. This suggests that the divergence of E6 proteins from either MAML1 or E6AP binding preference is a major event in papillomavirus evolution. PMID:29281732

Dexamethasone inhibits IL-12p40 production in lipopolysaccharide-stimulated human monocytic cells by down-regulating the activity of c-Jun N-terminal kinase, the activation protein-1, and NF-kappa B transcription factors.

PubMed

Ma, Wei; Gee, Katrina; Lim, Wilfred; Chambers, Kelly; Angel, Jonathan B; Kozlowski, Maya; Kumar, Ashok

2004-01-01

IL-12 plays a critical role in the development of cell-mediated immune responses and in the pathogenesis of inflammatory and autoimmune disorders. Dexamethasone (DXM), an anti-inflammatory glucocorticoid, has been shown to inhibit IL-12p40 production in LPS-stimulated monocytic cells. In this study, we investigated the molecular mechanism by which DXM inhibits IL-12p40 production by studying the role of the mitogen-activated protein kinases (MAPKs), and the key transcription factors involved in human IL-12p40 production in LPS-stimulated monocytic cells. A role for c-Jun N-terminal kinase (JNK) MAPK in LPS-induced IL-12p40 regulation in a promonocytic THP-1/CD14 cell line was demonstrated by using specific inhibitors of JNK activation, SP600125 and a dominant-negative stress-activated protein/extracellular signal-regulated kinase kinase-1 mutant. To identify transcription factors regulating IL-12p40 gene transcription, extensive deletion analyses of the IL-12p40 promoter was performed. The results revealed the involvement of a sequence encompassing the AP-1-binding site, in addition to that of NF-kappaB. The role of AP-1 in IL-12p40 transcription was confirmed by using antisense c-fos and c-jun oligonucleotides. Studies conducted to understand the regulation of AP-1 and NF-kappaB activation by JNK MAPK revealed that both DXM and SP600125 inhibited IL-12p40 gene transcription by inhibiting the activation of AP-1 and NF-kappaB transcription factors as revealed by luciferase reporter and gel mobility shift assays. Taken together, our results suggest that DXM may inhibit IL-12p40 production in LPS-stimulated human monocytic cells by down-regulating the activation of JNK MAPK, the AP-1, and NF-kappaB transcription factors.

Identification and characterization of a transient outward K+ current in human induced pluripotent stem cell-derived cardiomyocytes

PubMed Central

Cordeiro, Jonathan M.; Nesterenko, Vladislav V.; Sicouri, Serge; Goodrow, Robert J.; Treat, Jacqueline A.; Desai, Mayurika; Wu, Yuesheng; Doss, Michael Xavier; Antzelevitch, Charles; Di Diego, José M.

2013-01-01

Background The ability to recapitulate mature adult phenotypes is critical to the development of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) as models of disease. The present study examines the characteristics of the transient outward current (Ito) and its contribution to the hiPSC-CM action potential (AP). Method Embryoid bodies were made from a hiPS cell line reprogrammed with Oct4, Nanog, Lin28 and Sox2. Sharp microelectrodes were used to record APs from beating-clusters (BC) and patch-clamp techniques were used to record Ito in single hiPSC-CM. mRNA levels of Kv1.4, KChIP2 and Kv4.3 were quantified from BCs. Results BCs exhibited spontaneous beating (60.5 ± 2.6 bpm) and maximum-diastolic-potential (MDP) of 67.8 ± 0.8 mV (n = 155). A small 4-aminopyridine-sensitive phase-1-repolarization was observed in only 6/155 BCs. A robust Ito was recorded in the majority of cells (13.7 ± 1.9 pA/pF at +40 mV; n = 14). Recovery of Ito from inactivation (at −80 mV) showed slow kinetics (τ1 = 200 ± 110 ms (12%) and τ2 = 2380 ± 240 ms (80%)) accounting for its minimal contribution to the AP. Transcript data revealed relatively high expression of Kv1.4 and low expression of KChIP2 compared to human native ventricular tissues. Mathematical modeling predicted that restoration of IK1 to normal levels would result in a more negative MDP and a prominent phase-1-repolarization. Conclusion The slow recovery kinetics of Ito coupled with a depolarized MDP account for the lack of an AP notch in the majority of hiPSC-CM. These characteristics reveal a deficiency for the development of in vitro models of inherited cardiac arrhythmia syndromes in which Ito-induced AP notch is central to the disease phenotype. PMID:23542310

Approximate entropy of human respiratory movement during eye-closed waking and different sleep stages.

PubMed

Burioka, Naoto; Cornélissen, Germaine; Halberg, Franz; Kaplan, Daniel T; Suyama, Hisashi; Sako, Takanori; Shimizu, Eiji

2003-01-01

The breath-to-breath variability of respiratory parameters changes with sleep stage. This study investigates any alteration in the approximate entropy (ApEn) of respiratory movement as a gauge of complexity in respiration, by stage of consciousness, in the light of putative brain interactions. Eight healthy men, who were between the ages of 23 and 29 years, were investigated. The signals of chest wall movement and EEG were recorded from 10:30 PM to 6:00 AM. After analog-to-digital conversion, the ApEn of respiratory movement (3 min) and EEG (20 s) were computed. Surrogate data were tested for nonlinearity in the original time series. The most impressive reduction in the ApEn of respiratory movement was associated with stage IV sleep, when the ApEn of the EEG was also statistically significantly decreased. A statistically significant linear relation is found between the ApEn of both variables. Surrogate data indicated that respiratory movement had nonlinear properties during all stages of consciousness that were investigated. Respiratory movement and EEG signals are more regular during stage IV sleep than during other stages of consciousness. The change in complexity described by the ApEn of respiration depends in part on the ApEn of the EEG, suggesting the involvement of nonlinear dynamic processes in the coordination between brain and lungs.

Intracortical myelination in musicians with absolute pitch: Quantitative morphometry using 7-T MRI.

PubMed

Kim, Seung-Goo; Knösche, Thomas R

2016-10-01

Absolute pitch (AP) is known as the ability to recognize and label the pitch chroma of a given tone without external reference. Known brain structures and functions related to AP are mainly of macroscopic aspects. To shed light on the underlying neural mechanism of AP, we investigated the intracortical myeloarchitecture in musicians with and without AP using the quantitative mapping of the longitudinal relaxation rates with ultra-high-field magnetic resonance imaging at 7 T. We found greater intracortical myelination for AP musicians in the anterior region of the supratemporal plane, particularly the medial region of the right planum polare (PP). In the same region of the right PP, we also found a positive correlation with a behavioral index of AP performance. In addition, we found a positive correlation with a frequency discrimination threshold in the anterolateral Heschl's gyrus in the right hemisphere, demonstrating distinctive neural processes of absolute recognition and relative discrimination of pitch. Regarding possible effects of local myelination in the cortex and the known importance of the anterior superior temporal gyrus/sulcus for the identification of auditory objects, we argue that pitch chroma may be processed as an identifiable object property in AP musicians. Hum Brain Mapp 37:3486-3501, 2016. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

AP-1/σ1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory

PubMed Central

Glyvuk, Nataliya; Tsytsyura, Yaroslav; Geumann, Constanze; D'Hooge, Rudi; Hüve, Jana; Kratzke, Manuel; Baltes, Jennifer; Böning, Daniel; Klingauf, Jürgen; Schu, Peter

2010-01-01

Synaptic vesicle recycling involves AP-2/clathrin-mediated endocytosis, but it is not known whether the endosomal pathway is also required. Mice deficient in the tissue-specific AP-1–σ1B complex have impaired synaptic vesicle recycling in hippocampal synapses. The ubiquitously expressed AP-1–σ1A complex mediates protein sorting between the trans-Golgi network and early endosomes. Vertebrates express three σ1 subunit isoforms: A, B and C. The expressions of σ1A and σ1B are highest in the brain. Synaptic vesicle reformation in cultured neurons from σ1B-deficient mice is reduced upon stimulation, and large endosomal intermediates accumulate. The σ1B-deficient mice have reduced motor coordination and severely impaired long-term spatial memory. These data reveal a molecular mechanism for a severe human X-chromosome-linked mental retardation. PMID:20203623

AP-1/KIF13A Blocking Peptides Impair Melanosome Maturation and Melanin Synthesis.

PubMed

Campagne, Cécile; Ripoll, Léa; Gilles-Marsens, Floriane; Raposo, Graça; Delevoye, Cédric

2018-02-14

Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells. Incubating these peptides with human MNT-1 cells or 3D-reconstructed pigmented epidermis decreases pigmentation by impacting the maturation of melanosomes in fully pigmented organelles. This study highlights that peptides targeting the intracellular trafficking of melanocytes are candidate molecules to tune pigmentation in health and disease.

AP-1/KIF13A Blocking Peptides Impair Melanosome Maturation and Melanin Synthesis

PubMed Central

Campagne, Cécile; Ripoll, Léa; Gilles-Marsens, Floriane; Raposo, Graça

2018-01-01

Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells. Incubating these peptides with human MNT-1 cells or 3D-reconstructed pigmented epidermis decreases pigmentation by impacting the maturation of melanosomes in fully pigmented organelles. This study highlights that peptides targeting the intracellular trafficking of melanocytes are candidate molecules to tune pigmentation in health and disease. PMID:29443872

Interested and Influential: The Role of a Professional Association in the Development of the Foundation to Year 10 Australian Curriculum: Geography

ERIC Educational Resources Information Center

Caldis, Susan

2014-01-01

The Australian Geography Teachers Association (AGTA) represents the views of Australian geography teachers on educational matters. AGTA also seeks to improve the capacity of geography teachers to respond to a changing teaching and learning landscape. The Australian Curriculum, Assessment and Reporting Authority (ACARA) is an independent authority…

Teacher Education Models in Geography: An International Comparison. Papers Prepared in Conjunction with the International Geographical Union Congress (25th, 1984).

ERIC Educational Resources Information Center

Marsden, Wm., Ed.

Thirteen essays discussing how teachers are trained to teach geography in various countries are presented. The papers are: "Teacher Education in Geography: The Comparative View" (W. E. Marsden); "The Training of Geography Teachers in the People's Republic of Bulgaria" (Paulina Vekilska and Dimitar Kantchev); "Note Sur la…

Implementation of Geographic Information System (GIS) in Secondary Geography Curriculum in Hong Kong: Current Situations and Future Directions

ERIC Educational Resources Information Center

Lam, Chi-Chung; Lai, Edith; Wong, Janice

2009-01-01

Using geographic information system (GIS) in teaching and learning geography is an important direction in the secondary geography curriculum in Hong Kong. In the present study, interviews were conducted individually with 28 geography teachers from different secondary schools in Hong Kong, with a view to finding their views on the inclusion of GIS…

Placing Geography in the Curriculum: Ideas from the Western PLACE Conference (Boulder, Colorado, August 9-11, 1987).

ERIC Educational Resources Information Center

Hill, David A., Ed.

Primarily a collection of lesson plans covering various topics in geography, this document is divided into seven sections. The first section includes three short papers on geography and its place in the curriculum. The second section deals with teaching map skills, evaluating computer software to be used in teaching geography, and ideas for field…

Understanding Our World through Geography. Activities To Improve Geography Skills and Promote Ecology.

ERIC Educational Resources Information Center

Aten, Jerry

This book focuses on improving geography skills and knowledge of basic concepts for grades 4-8, through a variety of activities and resources. The book is divided into six sections that combine to make it convenient for use. The sections include: (1) "Map Reading Skills"; (2) "Geography Concepts and Definitions"; (3) "Peoples of the World"; (4) "A…

Evaluation of a commercial automatic treatment planning system for liver stereotactic body radiation therapy treatments.

PubMed

Gallio, Elena; Giglioli, Francesca Romana; Girardi, Andrea; Guarneri, Alessia; Ricardi, Umberto; Ropolo, Roberto; Ragona, Riccardo; Fiandra, Christian

2018-02-01

Automated treatment planning is a new frontier in radiotherapy. The Auto-Planning module of the Pinnacle 3 treatment planning system (TPS) was evaluated for liver stereotactic body radiation therapy treatments. Ten cases were included in the study. Six plans were generated for each case by four medical physics experts. The first two planned with Pinnacle TPS, both with manual module (MP) and Auto-Planning one (AP). The other two physicists generated two plans with Monaco TPS (VM). Treatment plan comparisons were then carried on the various dosimetric parameters of target and organs at risk, monitor units, number of segments, plan complexity metrics and human resource planning time. The user dependency of Auto-Planning was also tested and the plans were evaluated by a trained physician. Statistically significant differences (Anova test) were observed for spinal cord doses, plan average beam irregularity, number of segments, monitor units and human planning time. The Fisher-Hayter test applied to these parameters showed significant statistical differences between AP e MP for spinal cord doses and human planning time; between MP and VM for monitor units, number of segments and plan irregularity; for all those between AP and VM. The two plans created by different planners with AP were similar to each other. The plans created with Auto-Planning were comparable to the manually generated plans. The time saved in planning enables the planner to commit more resources to more complex cases. The independence of the planner enables to standardize plan quality. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Health and equity in all policies in local government: processes and outcomes in two Norwegian municipalities.

PubMed

Von Heimburg, Dina; Hakkebo, Berit

2017-08-01

To identify key factors in implementing Health and Equity in All Policies (HEiAP) at the local level in two Norwegian municipalities in order to accelerate the progress of promoting health, well-being and equity in other local governments. This case study is presented as a narrative from policy-making processes in two Norwegian municipalities. The story is told from an insider perspective, with a focus on HEiAP policy makers in these two municipalities. The narrative identified key learning from implementing HEiAP at the local level, i.e. the importance of strengthening system and human capacities. System capacity is strengthened by governing HEiAP according to national legislation and a holistic governance system at the local level. Municipal plans are based on theory, evidence and local data. A 'main story' is developed to support the vision, defining joint societal goals and co-creation strategies. Policies are anchored by measuring and monitoring outcomes, sharing accountability and continuous dialogue to ensure political commitment. Human capacity is strengthened through participatory leadership, soft skills and health promotion competences across sectors. Health promotion competence at a strategic level in the organization, participation in professional networks, crowd sourcing toward common goals, and commitment through winning hearts and minds of politicians and other stakeholders are vital aspects. Our experience pinpoints the importance of strengthening system and human capacity in local governments. Further, we found it important to focus on the two strategic objectives in the European strategy 'Health 2020': (1) Improving health for all and reducing health inequalities; (2) improving leadership and participatory governance for health.

Effects of butyltin exposures on MAP kinase dependent transcription regulators in human natural killer cells

PubMed Central

Person, Rachel J.; Whalen, Margaret M.

2010-01-01

Natural Killer (NK) cells are a major immune defense mechanism against cancer development and viral infection. The butyltins (BTs), tributyltin (TBT) and dibutyltin (DBT) have been widely used in industrial and other applications and significantly contaminate the environment. Both TBT and DBT have been detected in human blood. These compounds inhibit the lytic and binding function of human NK cells and thus could increase the incidence of cancer and viral infections. Butyltin (BT)-induced loss of NK function is accompanied by activation of mitogen activated protein kinases (MAPKs) and decreases in expression of cell-surface and cytolytic proteins. MAPKs activate components of the transcription regulator AP-1 and activate the transcription regulator Elk-1. Based on the fact that BTs activate MAPKs and alter protein expression, the current study examined the effect of BT exposures on the levels and phosphorylation states of the components of AP-1 and the phosphorylation state of Elk-1. Exposure to 300 nM TBT for 10 min increased the phosphorylation of c-Jun in NK cells. 1 h exposures to 300 nM and 200 nM TBT increased the phosphorylation and overall level of c-Jun. During a 300 nM treatment with TBT for 1 h the binding activity of AP-1 was significantly decreased. There were no significant alterations of AP-1 components or of Elk-1 with DBT exposures. Thus, it appears that TBT-induced alterations on phosphorylation, total levels and binding activity of c-Jun might contribute to, but are not fully responsible for, TBT-induced alterations of NK protein expression. PMID:20370538

Effects of butyltin exposures on MAP kinase-dependent transcription regulators in human natural killer cells.

PubMed

Person, Rachel J; Whalen, Margaret M

2010-06-01

Natural killer (NK) cells are a major immune defense mechanism against cancer development and viral infection. The butyltins (BTs), tributyltin (TBT) and dibutyltin (DBT), have been widely used in industrial and other applications and significantly contaminate the environment. Both TBT and DBT have been detected in human blood. These compounds inhibit the lytic and binding function of human NK cells and thus could increase the incidence of cancer and viral infections. Butyltin (BT)-induced loss of NK function is accompanied by activation of mitogen activated protein kinases (MAPKs) and decreases in expression of cell-surface and cytolytic proteins. MAPKs activate components of the transcription regulator AP-1 and activate the transcription regulator Elk-1. Based on the fact that BTs activate MAPKs and alter protein expression, the current study examined the effect of BT exposures on the levels and phosphorylation states of the components of AP-1 and the phosphorylation state of Elk-1. Exposure to 300 nM TBT for 10 min increased the phosphorylation of c-Jun in NK cells. One hour exposures to 300 nM and 200 nM TBT increased the phosphorylation and overall level of c-Jun. During a 300 nM treatment with TBT for 1 h the binding activity of AP-1 was significantly decreased. There were no significant alterations of AP-1 components or of Elk-1 with DBT exposures. Thus, it appears that TBT-induced alterations on phosphorylation, total levels, and binding activity of c-Jun might contribute to, but are not fully responsible for, TBT-induced alterations of NK protein expression.

Unexpected extent of immunochemical cross-reactions between rabbit and human serum proteins

PubMed Central

Johnson, P. K.; Yoder, J. M.

1970-01-01

Precipitin experiments indicated an unexpected extent of immunochemical cross-reactions between rabbit and human serum proteins. Commerical goat or horse antisera to human or rabbit serum were used. Two of the proteins involved in the cross-reactions were lipoproteins. Imagesp294-ap296-a PMID:4991121

Networks, narratives and territory in anthropological race classification: towards a more comprehensive historical geography of Europe's culture.

PubMed

McMahon, Richard

2011-01-01

This article aims to integrate discourse analysis of politically instrumental imagined identity geographies with the relational and territorial geography of the communities of praxis and interpretation that produce them. My case study is the international community of nationalist scientists who classified Europe's biological races in the 1820s-1940s. I draw on network analysis, relational geography, historical sociology and the historical turn to problematize empirically how spatial patterns of this community's shifting disciplinary and political coalitions, communication networks and power relations emerged, were structured, persisted, changed, interacted and disappeared. I focus especially on core-periphery relations. I argue that if local historical spatial patterns affect those of later phenomena, geographies like that of European integration should be understood in the context of Europe's complex historical cultural geography. Unlike discourse deconstruction alone, this complementary relational de-essentialization of geography can identify large-scale, enduring associations of cultural patterns as well as cultural flux and ambiguity.

Analysis of TFAP2A mutations in Branchio-Oculo-Facial Syndrome indicates functional complexity within the AP-2α DNA-binding domain

PubMed Central

Li, Hong; Sheridan, Ryan; Williams, Trevor

2013-01-01

Multiple lines of evidence indicate that the AP-2 transcription factor family has an important regulatory function in human craniofacial development. Notably, mutations in TFAP2A, the gene encoding AP-2α, have been identified in patients with Branchio-Oculo-Facial Syndrome (BOFS). BOFS is an autosomal-dominant trait that commonly presents with facial clefting, eye defects and branchial skin anomalies. Examination of multiple cases has suggested either simple haploinsufficiency or more complex genetic causes for BOFS, especially as the clinical manifestations are variable, with no clear genotype–phenotype correlation. Mutations occur throughout TFAP2A, but mostly within conserved sequences within the DNA contact domain of AP-2α. However, the consequences of the various mutations for AP-2α protein function have not been evaluated. Therefore, it remains unclear if all BOFS mutations result in similar changes to the AP-2α protein or if they each produce specific alterations that underlie the spectrum of phenotypes. Here, we have investigated the molecular consequences of the mutations that localize to the DNA-binding region. We show that although individual mutations have different effects on DNA binding, they all demonstrate significantly reduced transcriptional activities. Moreover, all mutant derivatives have an altered nuclear:cytoplasmic distribution compared with the predominantly nuclear localization of wild-type AP-2α and several can exert a dominant-negative activity on the wild-type AP-2α protein. Overall, our data suggest that the individual TFAP2A BOFS mutations can generate null, hypomorphic or antimorphic alleles and that these differences in activity, combined with a role for AP-2α in epigenetic events, may influence the resultant pathology and the phenotypic variability. PMID:23578821

Influence of waveform and current direction on short-interval intracortical facilitation: a paired-pulse TMS study.

PubMed

Delvendahl, Igor; Lindemann, Hannes; Jung, Nikolai H; Pechmann, Astrid; Siebner, Hartwig R; Mall, Volker

2014-01-01

Transcranial magnetic stimulation (TMS) of the human primary motor hand area (M1-HAND) can produce multiple descending volleys in fast-conducting corticospinal neurons, especially so-called indirect waves (I-waves) resulting from trans-synaptic excitation. Facilitatory interaction between these I-waves can be studied non-invasively using a paired-pulse paradigm referred to as short-interval intracortical facilitation (SICF). We examined whether SICF depends on waveform and current direction of the TMS pulses. In young healthy volunteers, we applied single- and paired-pulse TMS to M1-HAND. We probed SICF by pairs of monophasic or half-sine pulses at suprathreshold stimulation intensity and inter-stimulus intervals (ISIs) between 1.0 and 5.0 ms. For monophasic paired-pulse stimulation, both pulses had either a posterior-anterior (PA) or anterior-posterior (AP) current direction (AP-AP or PA-PA), whereas current direction was reversed between first and second pulse for half-sine paired-pulse stimulation (PA-AP and AP-PA). Monophasic AP-AP stimulation resulted in stronger early SICF at 1.4 ms relative to late SICF at 2.8 and 4.4 ms, whereas monophasic PA-PA stimulation produced SICF of comparable size at all three peaks. With half-sine stimulation the third SICF peak was reduced for PA-AP current orientation compared with AP-PA. SICF elicited using monophasic as well as half-sine pulses is affected by current direction at clearly suprathreshold intensities. The impact of current orientation is stronger for monophasic compared with half-sine pulses. The direction-specific effect of paired-pulse TMS on the strength of early versus late SICF shows that different cortical circuits mediate early and late SICF. Copyright © 2014 Elsevier Inc. All rights reserved.

Gathering "wild" food in the city: rethinking the role of foraging in urban ecosystem planning and management

Treesearch

Rebecca J. McLain; Patrick T. Hurley; Marla R. Emery; Melissa R. Poe

2014-01-01

Recent "green" planning initiatives envision food production, including urban agriculture and livestock production, as desirable elements of sustainable cities. We use an integrated urban political ecology and human-plant geographies framework to explore how foraging for "wild" foods in cities, a subversive practice that challenges prevailing views...

Society, the City and the Space-Economy of Urbanism, Resource Paper No. 18.

ERIC Educational Resources Information Center

Harvey, David

Theoretical concepts of spatial organization appropriate to bringing about humanizing social change are identified. This resource paper is part of a series designed to supplement existing texts and to fill a gap between research and accessible materials in geography. Part 1, societies and cities, introduces three basic forms of society:…

Academy-Community Partnerships: Challenges and Changes in Israeli Urban Regeneration Projects

ERIC Educational Resources Information Center

Tal, Rinat Botbol; Fenster, Tovi; Kulka, Tal

2015-01-01

Students worked with low-income Jaffa residents on a 3-year building renewal project as part of a multidisciplinary clinic operated through the collaboration of the Faculty of Law, the Department of Geography at the Faculty of Humanities, and the Faculty of Management at Tel-Aviv University. Alternative models in the legal and planning literature…

Reflections on the ESRC Internship Scheme for Postgraduates

ERIC Educational Resources Information Center

Bos, Daniel; Finlay, Robin; Hopkins, Peter; Lloyd, Jenny; Richardson, Michael

2017-01-01

The Economic and Social Research Council (ESRC) in the UK is one of the main sources of funding for postgraduate study in human geography. For some years now, the ESRC has offered funded students the opportunity to apply to undertake a short internship in a government department or with a Non-Governmental Organization (NGO). This paper provides a…

Social Science Pre-Service Teachers' Preparation to Teach about Asia: A Research Study

ERIC Educational Resources Information Center

Kenna, Joshua L.; Poole, Cyndi Mottola

2017-01-01

Asia is the world's largest continent, both in terms of land mass and human population; yet, many of the schools in the United States still embrace a Eurocentric curriculum, and resultantly, U.S. citizens remain largely ignorant about topics pertaining to Asian nations including their geography, histories, politics, economics, religions, and…

Panel Discussion: Stocktypes for Outplanting in Zion National Park

Treesearch

Cheryl Decker

2006-01-01

Zion National Park is located in southwestern Utah at the junction of three geographic regions: the Mojave Desert, the Great Basin, and the Colorado Plateau. This unique geography creates distinctive habitats in Zion. With the Virgin River running through the middle of the park, Zion is a refuge for plants, animals, and humans as well.

Effects of roads on wildlife in Arizona: How far have we traveled?

Treesearch

Hsiang Ling Chen; John L. Koprowski

2013-01-01

Roads are conspicuous and pervasive features of landscapes and represent one of the most significant anthropogenic impacts on natural areas and wildlife. The Madrean Archipelago is defined by natural levels of fragmentation due to geography; however, human population growth and transportation needs threaten to exacerbate levels of isolation in the region. Scientists,...

Inhibitory effect on activator protein-1, nuclear factor-kappaB, and cell transformation by extracts of strawberries (Fragaria x ananassa Duch.).

PubMed

Wang, Shiow Y; Feng, Rentian; Lu, Yongju; Bowman, Linda; Ding, Min

2005-05-18

The inhibitory effects of strawberry (Fragaria x ananassa Duch.) antioxidant enzymes on tetradecanoylphorbol-13-acetate (TPA) or ultraviolet-B (UVB) induced activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) were studied. The inhibitory effects of strawberry extracts on the proliferation and transformation of human and mouse cancer cells were also evaluated. Strawberries had high activities of glutathione peroxidase, superoxide dismutase, guaiacol peroxidase, ascorbate peroxidase, and glutathione reductase. Strawberry extracts inhibited the proliferation of human lung epithelial cancer cell line A549 and decreased TPA-induced neoplastic transformation of JB6 P+ mouse epidermal cells. Pretreatment of JB6 P+ mouse epidermal cells with strawberry extract resulted in the inhibition of both UVB- and TPA-induced AP-1 and NF-kappaB transactivation. Furthermore, strawberry extract also blocked TPA-induced phosphorylation of extracellular signal-regulated kinases (ERKs) and UVB-induced phosphorylation of ERKs and JNK kinase in JB6 P+ mouse epidermal cell culture. These results suggest that the ability of strawberries to block UVB- and TPA-induced AP-1 and NF-kappaB activation may be due to their antioxidant properties and their ability to reduce oxidative stress. The oxidative events that regulate AP-1 and NF-kappaB transactivation can be important molecular targets for cancer prevention. The strawberries may be highly effective as a chemopreventive agent that acts by targeting the down-regulation of AP-1 and NF-kappaB activities, blocking MAPK signaling, and suppressing cancer cell proliferation and transformation.

Developmental changes in electrophysiological characteristics of human induced Pluripotent Stem Cell-derived cardiomyocytes

PubMed Central

Ben-Ari, Meital; Naor, Shulamit; Zeevi-Levin, Naama; Schick, Revital; Ben Jehuda, Ronen; Reiter, Irina; Raveh, Amit; Grijnevitch, Inna; Barak, Omri; Rosen, Michael R.; Weissman, Amir; Binah, Ofer

2016-01-01

Background Previous studies proposed that throughout differentiation of human induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs) only 3 types of action potentials (AP) exist: nodal, atrial and ventricular-like. Objective To investigate whether there are precisely 3 phenotypes or a continuum exists among them, we tested 2 hypotheses: (1) during culture development a cardiac precursor cell is present that - depending on age - can evolve into the 3 phenotypes. (2) The predominant pattern is early prevalence of nodal phenotype, transient appearance of atrial phenotype, evolution to ventricular phenotype, and persistence of transitional phenotypes. Methods To test these hypotheses we: (1) performed FACS analysis of nodal, atrial and ventricular markers; (2) recorded AP from 280 7-to-95 day old iPSC-CMs; (3) analyzed AP characteristics. Results The major findings were: (1) FACS analysis of 30 and 60-day old cultures showed that an iPSC-CMs population shifts from nodal into atrial/ventricular phenotype, while including significant transitional populations.(2) The AP population did not consist of 3 distinct phenotypes; (3) Culture aging was associated with a shift from nodal to ventricular dominance, with a transient (57–70 days) appearance of atrial phenotype; (4) Beat Rate Variability was more prominent in nodal than ventricular cardiomyocytes while If density increased in older cultures. Conclusions From the onset of development the iPSC-CMs population includes nodal, atrial and ventricular AP and a broad spectrum of transitional phenotypes. The most readily distinguishable phenotype is atrial which appears only transiently, yet dominates at 57–70 days of evolution. PMID:27639456

Regulation of human bone sialoprotein gene transcription by platelet-derived growth factor-BB.

PubMed

Mezawa, Masaru; Araki, Shouta; Takai, Hideki; Sasaki, Yoko; Wang, Shuang; Li, Xinyue; Kim, Dong-Soon; Nakayama, Youhei; Ogata, Yorimasa

2009-04-15

Platelet-derived growth factor (PDGF) is produced by mesenchymal cells and released by platelets following aggregation and is synthesized by osteoblasts. In bone, PDGF stimulates proliferation and differentiation of osteoblasts. PDGF also increases bone resorption, most likely by increasing the number of osteoclasts. Bone sialoprotein (BSP) is thought to function in the initial mineralization of bone, selectively expressed by differentiated osteoblast. To determine the molecular mechanisms PDGF regulation of human BSP gene transcription, we have analyzed the effects of PDGF-BB on osteoblast-like Saos2 and ROS17/2.8 cells. PDGF-BB (5 ng/ml) increased BSP mRNA and protein levels at 12 h in Saos2 cells, and induced BSP mRNA expression at 3 h, reached maximal at 12 h in ROS17/2.8 cells. Transient transfection analyses were performed using chimeric constructs of the human BSP gene promoter linked to a luciferase reporter gene. Treatment of Saos2 cells with PDGF-BB (5 ng/ml, 12 h) increased luciferase activities of all constructs between -184LUC to -2672LUC including the human BSP gene promoter. Effects of PDGF-BB abrogated in constructs included 2 bp mutations in the two cAMP response elements (CRE1 and CRE2), activator protein 1(3) (AP1(3)) and shear stress response element 1 (SSRE1). Luciferase activities induced by PDGF-BB were blocked by protein kinase A inhibitor H89 and tyrosine kinase inhibitor herbimycin A. Gel mobility shift analyses showed that PDGF-BB increased binding of CRE1, CRE2, AP1(3) and SSRE1 elements. CRE1- and CRE2-protein complexes were supershifted by CREB1 and phospho-CREB1 antibodies. Notably, AP1(3)-protein complexes were supershifted by c-Fos and JunD, and disrupted by CREB1, phospho-CREB1, c-Jun and Fra2 antibodies. These studies, therefore, demonstrate that PDGF-BB stimulates human BSP transcription by targeting the CRE1, CRE2, AP1(3) and SSRE1 elements in the human BSP gene promoter.

Comparative Transcriptomics Highlights the Role of the Activator Protein 1 Transcription Factor in the Host Response to Ebolavirus

PubMed Central

Todd, Shawn; Boyd, Victoria; Tachedjian, Mary; Klein, Reuben; Shiell, Brian; Dearnley, Megan; McAuley, Alexander J.; Woon, Amanda P.; Purcell, Anthony W.; Marsh, Glenn A.; Baker, Michelle L.

2017-01-01

ABSTRACT Ebolavirus and Marburgvirus comprise two genera of negative-sense single-stranded RNA viruses that cause severe hemorrhagic fevers in humans. Despite considerable research efforts, the molecular events following Ebola virus (EBOV) infection are poorly understood. With the view of identifying host factors that underpin EBOV pathogenesis, we compared the transcriptomes of EBOV-infected human, pig, and bat kidney cells using a transcriptome sequencing (RNA-seq) approach. Despite a significant difference in viral transcription/replication between the cell lines, all cells responded to EBOV infection through a robust induction of extracellular growth factors. Furthermore, a significant upregulation of activator protein 1 (AP1) transcription factor complex members FOS and JUN was observed in permissive cell lines. Functional studies focusing on human cells showed that EBOV infection induces protein expression, phosphorylation, and nuclear accumulation of JUN and, to a lesser degree, FOS. Using a luciferase-based reporter, we show that EBOV infection induces AP1 transactivation activity within human cells at 48 and 72 h postinfection. Finally, we show that JUN knockdown decreases the expression of EBOV-induced host gene expression. Taken together, our study highlights the role of AP1 in promoting the host gene expression profile that defines EBOV pathogenesis. IMPORTANCE Many questions remain about the molecular events that underpin filovirus pathophysiology. The rational design of new intervention strategies, such as postexposure therapeutics, will be significantly enhanced through an in-depth understanding of these molecular events. We believe that new insights into the molecular pathogenesis of EBOV may be possible by examining the transcriptomic response of taxonomically diverse cell lines (derived from human, pig, and bat). We first identified the responsive pathways using an RNA-seq-based transcriptomics approach. Further functional and computational analysis focusing on human cells highlighted an important role for the AP1 transcription factor in mediating the transcriptional response to EBOV infection. Our study sheds new light on how host transcription factors respond to and promote the transcriptional landscape that follows viral infection. PMID:28931675

The academic success of GIS in geography: Problems and prospects

NASA Astrophysics Data System (ADS)

Longley, Paul A.

The success of GIS has in some ways proved to be a mixed blessing to academic geography. While quantitative geography has developed as a disciplinary specialism over a long period of time, the infusion of GIS has been more rapid and applications-led. Geography has been a consumer, not producer, of mainstream GIS software, and as such GIS may even contribute towards accelerated de-skilling of the discipline. The technology nevertheless provides a crucial means of dealing with the current proliferation of digital data, and has important implications for the future development of geography.

Sex-specific genetic diversity is shaped by cultural factors in Inner Asian human populations.

PubMed

Marchi, Nina; Hegay, Tatyana; Mennecier, Philippe; Georges, Myriam; Laurent, Romain; Whitten, Mark; Endicott, Philipp; Aldashev, Almaz; Dorzhu, Choduraa; Nasyrova, Firuza; Chichlo, Boris; Ségurel, Laure; Heyer, Evelyne

2017-04-01

Sex-specific genetic structures have been previously documented worldwide in humans, even though causal factors have not always clearly been identified. In this study, we investigated the impact of ethnicity, geography and social organization on the sex-specific genetic structure in Inner Asia. Furthermore, we explored the process of ethnogenesis in multiple ethnic groups. We sampled DNA in Central and Northern Asia from 39 populations of Indo-Iranian and Turkic-Mongolic native speakers. We focused on genetic data of the Y chromosome and mitochondrial DNA. First, we compared the frequencies of haplogroups to South European and East Asian populations. Then, we investigated the genetic differentiation for eight Y-STRs and the HVS1 region, and tested for the effect of geography and ethnicity on such patterns. Finally, we reconstructed the male demographic history, inferred split times and effective population sizes of different ethnic groups. Based on the haplogroup data, we observed that the Indo-Iranian- and Turkic-Mongolic-speaking populations have distinct genetic backgrounds. However, each population showed consistent mtDNA and Y chromosome haplogroups patterns. As expected in patrilocal populations, we found that the Y-STRs were more structured than the HVS1. While ethnicity strongly influenced the genetic diversity on the Y chromosome, geography better explained that of the mtDNA. Furthermore, when looking at various ethnic groups, we systematically found a genetic split time older than historical records, suggesting a cultural rather than biological process of ethnogenesis. This study highlights that, in Inner Asia, specific cultural behaviors, especially patrilineality and patrilocality, leave a detectable signature on the sex-specific genetic structure. © 2017 Wiley Periodicals, Inc.

Mutagenicity of p-aminophenol in E. coli WP2uvrA/pKM101 and its relevance to oxidative DNA damage.

PubMed

Yoshida, R; Oikawa, S; Ogawa, Y; Miyakoshi, Y; Ooida, M; Asanuma, K; Shimizu, H

1998-07-08

It was recently reported that p-aminophenol (p-AP) induces DNA cleavage in mouse lymphoma cells, CHO cells and human lymphoblastoid cells. The mutagenicity of p-AP has not, however, been detected by reverse mutation assays. The purpose of this study was to assess the mutagenicity of p-AP by reverse mutation assay using Escherichia coli WP2uvrA/pKM101, which has a spectrum for detecting mutations different from those of other strains in the family with an AT base pair at the mutation site and has higher sensitivity to certain oxidative mutagens as compared to other strains. We found that p-AP was mutagenic to E. coli WP2uvrA/pKM101. The mutagenic activity of this compound was suppressed with the addition of dimethylsulfoxide or catalase, suggesting the involvement of active oxygen species in the mutagenic process induced by p-AP. To further elucidate the underlying mechanism, we used isolated DNA for the following experiments. It was revealed, by gel electrophoretic analysis, that p-AP induced DNA cleavage in the presence of Fe(III). However, p-AP alone did not induce this cleavage. Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by p-AP in calf thymus DNA was also detected in the presence of Fe(III) by HPLC with an electrochemical detector. ESR-spin trapping experiments using DMPO detected the production of hydroxyl radical (.OH) in the solution of p-AP with Fe(III). Both p-AP mediated DNA damages and .OH production by p-AP in the presence of Fe(III) were completely inhibited by .OH scavengers (ethanol, mannitol, sodium formate, dimethylsulfoxide) and catalase. These results suggest that .OH derived from the reaction between H2O2 and Fe(III) (Fenton reaction) participates in the oxidative DNA damage. Accordingly, the same mechanism might be working in E. coli WP2uvrA/pKM101 during induction of the mutation by p-AP.

Finding A Way: Encouraging Underrepresented Groups in Geography. An Annotated Bibliography. Pathways in Geography Series Resource Publication, Title No. 5.

ERIC Educational Resources Information Center

LeVasseur, Michal

This bibliography is intended to begin the process of awareness necessary to encourage young women and racial and ethnic minorities in geography classes across the nation. Women and minority racial and ethnic groups have long been seriously underrepresented in the discipline of geography both in the applied and professional world and in academic…

Gender Representation in Academic Geography in Catalonia (Spain): Towards a Masculinization of the Discipline? Symposium

ERIC Educational Resources Information Center

Dolors Garcia-Ramon, Maria; Pujol, Herminia

2004-01-01

In the mid-1980s Spanish geography seemed to be a success story in relation to gender and geography (Garcia-Ramon et al. , 1988 ). But in recent years this positive aspect has been less marked, at least in Catalan geography. The total percentage of women staff has remained quite steady but the male:female ratio has significantly increased among…

Educational Ideas in Geography Education in Sweden during the Nineteenth and Early Twentieth Centuries: The Relationship between Maps and Texts

ERIC Educational Resources Information Center

Hennerdal, Pontus

2015-01-01

Descriptions of the geography education of the nineteenth and early twentieth centuries in Sweden are typically offered to contrast with current ideas in geography education, and the content of geography textbooks is the focus of this comparison. The role of maps and visual pedagogy are ignored, and the educational ideas developed from regional…

Assessment of the Policy Guidelines for the Teaching and Learning of Geography at the Senior High School Level in Ghana

ERIC Educational Resources Information Center

Ababio, Bethel T.; Dumba, Hillary

2014-01-01

This article empirically assessed the extent to which geography teachers adhered to the Ghana Education Service policy guidelines on the teaching of geography at the Senior High School Level in Ghana. Census survey was used to collect data from seven geography teachers because of the researchers' objective of gaining a quick insight into the…

The present status of geography education in boys' intermediate schools of Riyadh, Saudi Arabia

NASA Astrophysics Data System (ADS)

Al-Gahtany, Abdulrahman Mohammed

The purpose of this study was to describe the present status of geography education in boys' intermediate schools in Riyadh, Saudi Arabia as perceived by geography teachers and supervisors; that is, to investigate the objectives, content, methods of teaching, tools and resources that are available and used in classrooms, evaluation techniques, and problems encountered in the teaching of geography. To collect data from this representative sample population, a questionnaire was developed by the researcher specifically for this study. Questionnaire data was collected from 19 social studies supervisors and 213 geography teachers. Percentages, frequencies, means, and standard deviations were computed for each questionnaire item. Chi Square tests were applied to determine if any significant differences could be identified between the observed and expected responses of supervisors and teachers. Major findings of the study indicated that both supervisors and teachers tend to strongly support the identified geography objectives. Most teachers and supervisors also indicated that the current geography curriculum contains enough information about Saudi Arabia, the Arabic world, and the Islamic world. In addition, the also indicated that geography content promotes a sense of patriotism and cultural pride. Responses indicated that educators see deficiencies in the content: it does not focus sufficiently on current events nor on developing student skills such as research and technical skills like drawing maps. Lecture and discussion are the most commonly used strategies in the teaching of geography. Field trips, role-playing, scientific competitions, scientific games, solving problems, and individual learning are less commonly used. Teaching tools most commonly used are wall maps and earth globes, whereas the use of geographical transparencies, models, and instruments is not common. Most of the teachers do lot use computers in their teaching. Evaluation techniques depend completely on traditional examinations to evaluate the performance of the students. Chi-square test shows that there are significant differences in observed and expected frequencies between teachers and supervisors with respect to geography learning objectives, geography content, methods of teaching, tools and resources, and the problems that geography teachers encounter in their teaching.

Absolute Pitch: Effects of Timbre on Note-Naming Ability

PubMed Central

Vanzella, Patrícia; Schellenberg, E. Glenn

2010-01-01

Background Absolute pitch (AP) is the ability to identify or produce isolated musical tones. It is evident primarily among individuals who started music lessons in early childhood. Because AP requires memory for specific pitches as well as learned associations with verbal labels (i.e., note names), it represents a unique opportunity to study interactions in memory between linguistic and nonlinguistic information. One untested hypothesis is that the pitch of voices may be difficult for AP possessors to identify. A musician's first instrument may also affect performance and extend the sensitive period for acquiring accurate AP. Methods/Principal Findings A large sample of AP possessors was recruited on-line. Participants were required to identity test tones presented in four different timbres: piano, pure tone, natural (sung) voice, and synthesized voice. Note-naming accuracy was better for non-vocal (piano and pure tones) than for vocal (natural and synthesized voices) test tones. This difference could not be attributed solely to vibrato (pitch variation), which was more pronounced in the natural voice than in the synthesized voice. Although starting music lessons by age 7 was associated with enhanced note-naming accuracy, equivalent abilities were evident among listeners who started music lessons on piano at a later age. Conclusions/Significance Because the human voice is inextricably linked to language and meaning, it may be processed automatically by voice-specific mechanisms that interfere with note naming among AP possessors. Lessons on piano or other fixed-pitch instruments appear to enhance AP abilities and to extend the sensitive period for exposure to music in order to develop accurate AP. PMID:21085598

Determination of trace alkaline phosphatase by affinity adsorption solid substrate room temperature phosphorimetry based on wheat germ agglutinin labeled with 8-quinolineboronic acid phosphorescent molecular switch and prediction of diseases

NASA Astrophysics Data System (ADS)

Liu, Jia-Ming; Gao, Hui; Li, Fei-Ming; Shi, Xiu-Mei; Lin, Chang-Qing; Lin, Li-Ping; Wang, Xin-Xing; Li, Zhi-Ming

2010-09-01

The 8-quinolineboronic acid phosphorescent molecular switch (abbreviated as PMS-8-QBA. Thereinto, 8-QBA is 8-quinolineboronic acid, and PMS is phosphorescent molecular switch) was found for the first time. PMS-8-QBA, which was in the "off" state, could only emit weak room temperature phosphorescence (RTP) on the acetyl cellulose membrane (ACM). However, PMS-8-QBA turned "on" automatically for its changed structure, causing that the RTP of 8-QBA in the system increased, after PMS-8-QBA-WGA (WGA is wheat germ agglutinin) was formed by reaction between -OH of PMS-8-QBA and -COOH of WGA. More interesting is that the -NH 2 of PMS-8-QBA-WGA could react with the -COOH of alkaline phosphatase (AP) to form the affinity adsorption (AA) product WGA-AP-WGA-8-QBA-PMS (containing -NH-CO- bond), which caused RTP of the system to greatly increase. Thus, affinity adsorption solid substrate room temperature phosphorimetry using PMS-8-QBA as labelling reagent (PMS-8-QBA-AA-SSRTP) for the determination of trace AP was established. The method had many advantages, such as high sensitivity (the detection limit (LD) was 2.5 zg spot -1. For sample volume of 0.40 μl spot -1, corresponding concentration was 6.2 × 10 -18 g ml -1), good selectivity (the allowed concentration of coexisting material was higher, when the relative error was ±5%), high accuracy (applied to detection of AP content in serum samples, the result was coincided with those obtained by enzyme-linked immunoassay), which was suitable for the detection of trace AP content in serum samples and the forecast of human diseases. Meanwhile, the mechanism of PMS-8-QBA-AASSRTP was discussed. The new field of analytical application and clinic diagnosis technique of molecule switch are exploited, based on the phosphorescence characteristic of PMS-8-QBA, the AA reaction between WGA and AP, as well as the relation between AP content and human diseases. The research results promote the development and interpenetrate among molecule switch technique, lectin science and SSRTP.

Determination of trace alkaline phosphatase by affinity adsorption solid substrate room temperature phosphorimetry based on wheat germ agglutinin labeled with 8-quinolineboronic acid phosphorescent molecular switch and prediction of diseases.

PubMed

Liu, Jia-Ming; Gao, Hui; Li, Fei-Ming; Shi, Xiu-Mei; Lin, Chang-Qing; Lin, Li-Ping; Wang, Xin-Xing; Li, Zhi-Ming

2010-09-01

The 8-quinolineboronic acid phosphorescent molecular switch (abbreviated as PMS-8-QBA. Thereinto, 8-QBA is 8-quinolineboronic acid, and PMS is phosphorescent molecular switch) was found for the first time. PMS-8-QBA, which was in the "off" state, could only emit weak room temperature phosphorescence (RTP) on the acetyl cellulose membrane (ACM). However, PMS-8-QBA turned "on" automatically for its changed structure, causing that the RTP of 8-QBA in the system increased, after PMS-8-QBA-WGA (WGA is wheat germ agglutinin) was formed by reaction between -OH of PMS-8-QBA and -COOH of WGA. More interesting is that the -NH(2) of PMS-8-QBA-WGA could react with the -COOH of alkaline phosphatase (AP) to form the affinity adsorption (AA) product WGA-AP-WGA-8-QBA-PMS (containing -NH-CO- bond), which caused RTP of the system to greatly increase. Thus, affinity adsorption solid substrate room temperature phosphorimetry using PMS-8-QBA as labelling reagent (PMS-8-QBA-AA-SSRTP) for the determination of trace AP was established. The method had many advantages, such as high sensitivity (the detection limit (LD) was 2.5zgspot(-1). For sample volume of 0.40mulspot(-1), corresponding concentration was 6.2x10(-18)gml(-1)), good selectivity (the allowed concentration of coexisting material was higher, when the relative error was +/-5%), high accuracy (applied to detection of AP content in serum samples, the result was coincided with those obtained by enzyme-linked immunoassay), which was suitable for the detection of trace AP content in serum samples and the forecast of human diseases. Meanwhile, the mechanism of PMS-8-QBA-AASSRTP was discussed. The new field of analytical application and clinic diagnosis technique of molecule switch are exploited, based on the phosphorescence characteristic of PMS-8-QBA, the AA reaction between WGA and AP, as well as the relation between AP content and human diseases. The research results promote the development and interpenetrate among molecule switch technique, lectin science and SSRTP. Copyright 2009 Elsevier B.V. All rights reserved.

Differentiation of Saccharomyces cerevisiae populations from vineyards of the Azores Archipelago: Geography vs Ecology.

PubMed

Drumonde-Neves, João; Franco-Duarte, Ricardo; Vieira, Eugénia; Mendes, Inês; Lima, Teresa; Schuller, Dorit; Pais, Célia

2018-09-01

Aiming to elucidate the roles that ecology and geography play in shaping the differentiation of fermentative grape-associated Saccharomyces cerevisiae populations, several locations on six islands of the Azores Archipelago were surveyed. A total of 249 strains were isolated from spontaneous fermentations of grape samples from several varieties of two distinct grapevine species (Vitis vinifera L. and Vitis labrusca L.), in vineyards that are under regular cultivation or in abandoned vineyards. Strains were genetically analyzed using a set of nine microsatellite loci, and also phenotypically characterized using relevant physiological/biotechnological tests. Results showed that genetic divergence among populations of the same island was lower than from populations from different islands. Phenotypic comparison of the populations from each of the islands revealed significant differences between them. Strains isolated from the islands with more intensive viticultural activity - Pico, Terceira and Graciosa - showed higher levels of SO 2 tolerance, possibly resulting from selection by human activity. The percentage of strains producing low levels of H 2 S was higher in S. Jorge (60%). Our findings were supported both by genetic and phenotypic data and provide clear evidence for the prevailing role of the geography over ecology in the differentiation of S. cerevisiae populations in the Azores Archipelago. Copyright © 2018. Published by Elsevier Ltd.

Effects of environmental estrogenic chemicals on AP1 mediated transcription with estrogen receptors alpha and beta.

PubMed

Fujimoto, Nariaki; Honda, Hiroaki; Kitamura, Shigeyuki

2004-01-01

There has been much discussion concerning endocrine disrupting chemicals suspected of exerting adverse effects in both wildlife and humans. Since the majority of these compounds are estrogenic, a large number of in vitro tests for estrogenic characteristics have been developed for screening purpose. One reliable and widely used method is the reporter gene assay employing estrogen receptors (ERs) and a reporter gene with a cis-acting estrogen responsive element (ERE). Other elements such as AP1 also mediate estrogenic signals and the manner of response could be quite different from that of ERE. Since this has yet to be explored, the ER mediated AP1 activity in response to a series of environmental estrogens was investigated in comparison with ERE findings. All the compounds exhibited estrogenic properties with ERE-luc and their AP1 responses were quite similar. These was one exception, however, p,p'-DDT (1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane) did not exert any AP1-luc activity, while it appeared to be estrogenic at 10(-7) to 10(-5)M with the ERE action. None of the compounds demonstrated ER beta:AP1 activity. These data suggest that significant differences can occur in responses through the two estrogen pathways depending on environmental chemicals.

Supplementation with Astragalus polysaccharides alters Aeromonas-induced tissue-specific cellular immune response.

PubMed

Abuelsaad, Abdelaziz S A

2014-01-01

Members of the genus Aeromonas inhabit various aquatic environments and are responsible for a number of intestinal and extra-intestinal infections in humans as well as other animals. Astragalus species are used in Chinese traditional medicine as antiperspirant, antihypertensive, diuretic and tonic treatments and have been used for treatment of patients with leukemia and uterine cancers. The present study was aimed to investigate immunomodulatory effect of Astragalus polysaccharides (APS) treatment on Aeromonas hydrophila-infected mice. The present data showed that APS-treatment ameliorated neutrophils phagocytic activity and reactive oxygen species (ROS) production in intestinal tissues of infected mice. Moreover, APS treatment induced a highly significantly (P < 0.001) increase in the number of CD4(+) T cells in the intestinal tissues and thymus, however, number of CD4(+) T cells in the spleens of infected mice not significantly changed with APS treatment. On the other hand, APS-treatment caused a very highly significant (P < 0.001) decrease in the number of CD8(+) T cells in the spleens and thymus of infected mice. In conclusion, the present data suggested that APS treatment reduced ROS production, downmodulated neutrophils activity, and increased CD4(+)/CD8(+) T cells ratio in A. hydrophila-infected mice. Copyright © 2014 Elsevier Ltd. All rights reserved.

The interaction between HIV-1 Nef and adaptor protein-2 reduces Nef-mediated CD4+ T cell apoptosis.

PubMed

Jacob, Rajesh Abraham; Johnson, Aaron L; Pawlak, Emily N; Dirk, Brennan S; Van Nynatten, Logan R; Haeryfar, S M Mansour; Dikeakos, Jimmy D

2017-09-01

Acquired Immune Deficiency Syndrome is characterized by a decline in CD4 + T cells. Here, we elucidated the mechanism underlying apoptosis in Human Immunodeficiency Virus-1 (HIV-1) infection by examining host apoptotic pathways hijacked by the HIV-1 Nef protein in the CD4 + T-cell line Sup-T1. Using a panel of Nef mutants unable to bind specific host proteins we uncovered that Nef generates pro- and anti-apoptotic signals. Apoptosis increased upon mutating the motifs involved in the interaction of Nef:AP-1 (Nef M20A or Nef EEEE62-65AAAA ) or Nef:AP-2 (Nef LL164/165AA ), implying these interactions limit Nef-mediated apoptosis. In contrast, disrupting the Nef:PAK2 interaction motifs (Nef H89A or Nef F191A ) reduced apoptosis. To validate further, apoptosis was measured after short-hairpin RNA knock-down of AP-1, AP-2 and PAK2. AP-2α depletion enhanced apoptosis, demonstrating that disrupting the Nef:AP-2α interaction limits Nef-mediated apoptosis. Collectively, we describe a mechanism by which HIV-1 regulates cell survival and demonstrate the consequence of interfering with Nef:host protein interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

Introductory Disciplines of Astronomy in Undergraduation Geography in Brazilian Public Universities

NASA Astrophysics Data System (ADS)

Henrique Azevedo Sobreira, Paulo

2015-08-01

There are some previous works about introductory disciplines of Astronomy in higher education in various undergraduation at Brazilian universities, but this is a specific research for Geography courses in public universities. Some undergraduate courses in Geography in Brazil offer introductory disciplines of Astronomy, since the second half of the twentieth century. This work presents an updated survey on the topic, and it proposes an effort at the national level, for the benefit of the increase in introductory disciplines of Astronomy in undergraduation in Geography. The data collected from public universities were obtained from the consultation of the websites of state universities, federal and county in 2012, 2013 and 2015, for information on the Geography courses and, among them, those with disciplines of Astronomy. The results show that there are 94 undergraduation in Geography courses in public universities, 12 of them had introductory disciplines of Astronomy until 2012 and 2013. In 2015 three of these disciplines were canceled which reduced to 9 universities. There were 23 undergraduation in Geography courses in 10 bachelor degrees and 14 education degrees with Astronomy disciplines. At 2015 it decreased to 20 in 5 bachelors and 8 education degrees. There are two undergraduation Geography courses with two introductory disciplines of Astronomy, while the other 18 offer only one discipline. The inclusion of introductory disciplines of Astronomy depends on the actions of professors' groups who works in undergraduation Geography courses, and of the astronomers initiative to offering them. The ideal is that the astronomers who actuate like professors in universities, normally in Math, Physics, Technologies, Enginnering and Science courses, they would can help and offer introductory disciplines in Astronomy for undergraduation in Geography courses.

Synthesis of Barbiturate-Based Methionine Aminopeptidase-1 Inhibitors

PubMed Central

Haldar, Manas K.; Scott, Michael D.; Sule, Nitesh; Srivastava, D. K.; Mallik, Sanku

2008-01-01

The syntheses of a new class of barbiturate-based inhibitors for human and E. Coli Methionine Aminopeptidase -1 (MetAP-1) are described. Some of the synthesized inhibitors show selective inhibition of the human enzyme with high potency. PMID:18343108

Y-Chromosomal Diversity in Europe Is Clinal and Influenced Primarily by Geography, Rather than by Language

PubMed Central

Rosser, Zoë H.; Zerjal, Tatiana; Hurles, Matthew E.; Adojaan, Maarja; Alavantic, Dragan; Amorim, António; Amos, William; Armenteros, Manuel; Arroyo, Eduardo; Barbujani, Guido; Beckman, Gunhild; Beckman, Lars; Bertranpetit, Jaume; Bosch, Elena; Bradley, Daniel G.; Brede, Gaute; Cooper, Gillian; Côrte-Real, Helena B. S. M.; de Knijff, Peter; Decorte, Ronny; Dubrova, Yuri E.; Evgrafov, Oleg; Gilissen, Anja; Glisic, Sanja; Gölge, Mukaddes; Hill, Emmeline W.; Jeziorowska, Anna; Kalaydjieva, Luba; Kayser, Manfred; Kivisild, Toomas; Kravchenko, Sergey A.; Krumina, Astrida; Kučinskas, Vaidutis; Lavinha, João; Livshits, Ludmila A.; Malaspina, Patrizia; Maria, Syrrou; McElreavey, Ken; Meitinger, Thomas A.; Mikelsaar, Aavo-Valdur; Mitchell, R. John; Nafa, Khedoudja; Nicholson, Jayne; Nørby, Søren; Pandya, Arpita; Parik, Jüri; Patsalis, Philippos C.; Pereira, Luísa; Peterlin, Borut; Pielberg, Gerli; Prata, Maria João; Previderé, Carlo; Roewer, Lutz; Rootsi, Siiri; Rubinsztein, D. C.; Saillard, Juliette; Santos, Fabrício R.; Stefanescu, Gheorghe; Sykes, Bryan C.; Tolun, Aslihan; Villems, Richard; Tyler-Smith, Chris; Jobling, Mark A.

2000-01-01

Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift. PMID:11078479

Independent Origins of Yeast Associated with Coffee and Cacao Fermentation.

PubMed

Ludlow, Catherine L; Cromie, Gareth A; Garmendia-Torres, Cecilia; Sirr, Amy; Hays, Michelle; Field, Colburn; Jeffery, Eric W; Fay, Justin C; Dudley, Aimée M

2016-04-04

Modern transportation networks have facilitated the migration and mingling of previously isolated populations of plants, animals, and insects. Human activities can also influence the global distribution of microorganisms. The best-understood example is yeasts associated with winemaking. Humans began making wine in the Middle East over 9,000 years ago [1, 2]. Selecting favorable fermentation products created specialized strains of Saccharomyces cerevisiae [3, 4] that were transported along with grapevines. Today, S. cerevisiae strains residing in vineyards around the world are genetically similar, and their population structure suggests a common origin that followed the path of human migration [3-7]. Like wine, coffee and cacao depend on microbial fermentation [8, 9] and have been globally dispersed by humans. Theobroma cacao originated in the Amazon and Orinoco basins of Colombia and Venezuela [10], was cultivated in Central America by Mesoamerican peoples, and was introduced to Europeans by Hernán Cortés in 1530 [11]. Coffea, native to Ethiopia, was disseminated by Arab traders throughout the Middle East and North Africa in the 6(th) century and was introduced to European consumers in the 17(th) century [12]. Here, we tested whether the yeasts associated with coffee and cacao are genetically similar, crop-specific populations or genetically diverse, geography-specific populations. Our results uncovered populations that, while defined by niche and geography, also bear signatures of admixture between major populations in events independent of the transport of the plants. Thus, human-associated fermentation and migration may have affected the distribution of yeast involved in the production of coffee and chocolate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Computer systems to support census geography.

PubMed

Deecker, G; Cunningham, R; Kidd, K

1986-01-01

The development of computer systems that support the geography of the census in Canada is described. The authors "present proposals for the 1991 Census that increase the level of automation, whether the geography changes or not. In addition, opportunities for change and improvement, should the geography change, are outlined. To minimize the risks involved, it is important to give these different proposals serious consideration early in the planning of a census." excerpt

Development of Geography Text Books Used by Senior High School Teachers Case Study at East Java-Indonesia

ERIC Educational Resources Information Center

Purwanto, Edy; Fatchan, Ach.; Purwanto; Soekamto, Hadi

2016-01-01

The aim of this study was to analyze the geography text book for: (1) identify and describe the errors in the organization of geography textbooks, and (2) identify and describe the content of the textbook standard errors of geography. The text book is currently being used by teachers of Senior High School in East Java. To analyze the contents of…

Use of the VIP-Man model to calculate energy imparted and effective dose for x-ray examinations.

PubMed

Winslow, Mark; Huda, Walter; Xu, X George; Chao, T C; Shi, C Y; Ogden, Kent M; Scalzetti, Ernest M

2004-02-01

A male human tomographic model was used to calculate values of energy imparted (epsilon) and effective dose (E) for monoenergetic photons (30-150 keV) in radiographic examinations. Energy deposition in the organs and tissues of the human phantom were obtained using Monte Carlo simulations. Values of E/epsilon were obtained for three common projections [anterior-posterior (AP), posterior-anterior (PA), and lateral (LAT)] of the head, cervical spine, chest, and abdomen, respectively. For head radiographs, all three projections yielded similar E/epsilon values. At 30 keV, the value of E/epsilon was approximately 1.6 mSv J(-1), which is increased to approximately 7 mSv J(-1) for 150 keV photons. The AP cervical spine was the only projection investigated where the value of E/epsilon decreased with increasing photon energy. Above 70 keV, cervical spine E/epsilon values showed little energy dependence and ranged between approximately 8.5 mSv J(-1) for PA projections and approximately 17 mSv J(-1) for AP projections. The values of E/epsilon for AP chest examinations showed very little variation with photon energy, and had values of approximately 23 mSv J(-1). Values of E/epsilon for PA and LAT chest projections were substantially lower than the AP projections and increased with increasing photon energy. For abdominal radiographs, differences between the PA and LAT projections were very small. All abdomen projections showed an increase in the E/epsilon ratio with increasing photon energy, and reached a maximum value of approximately 13.5 mSv J(-1) for AP projections, and approximately 9.5 mSv J(-1) for PA/lateral projections. These monoenergetic E/epsilon values can generate values of E/epsilon for any x-ray spectrum, and can be used to convert values of energy imparted into effective dose for patients undergoing common head and body radiological examinations.

NFκB- and AP-1-mediated DNA looping regulates matrix metalloproteinase-9 transcription in TNF-α-treated human leukemia U937 cells.

PubMed

Chen, Ying-Jung; Chang, Long-Sen

2015-10-01

The aim of this study is to explore the spatial association of critical genomic elements in the effect of TNF-α on matrix metalloproteinase-9 (MMP-9) expression in human leukemia U937 cells. TNF-α up-regulated MMP-9 protein expression and mRNA level in U937 cells, and Akt-mediated-NFκB/p65 activation and JNK-mediated c-Jun activation were proven to be involved in TNF-α-induced MMP-9 up-regulation. Promoter luciferase activity assay revealed that NFκB (nt-600) and AP-1 (nt-79) binding sites were crucial for TNF-α-induced transcription of MMP-9 gene. The results of a chromatin immunoprecipitation assay indicated that TNF-α reduced histone deacetylase-1 (HDAC-1) recruitment but increased p300 (a histone acetyltransferase) recruitment to MMP-9 promoter regions surrounding NFκB and AP-1 binding sites. Consistently, TNF-α increased enrichment of the acetylated histone H3 mark on MMP-9 promoter regions. DNA affinity purification assay revealed that p300 and HDAC1 could bind oligonucleotides containing AP-1/c-Jun and NFκB/p65 binding sites. Chromosome conformation capture assay showed that TNF-α stimulated chromosomal loops in the MMP-9 promoter via NFκB/p65 and AP-1/c-Jun. The p300-associated acetyltransferase activity was crucial for p65/c-Jun-mediated DNA looping, and inhibition of HDAC activity increased the level of DNA looping. Reduction in the level of DNA looping eliminated all TNF-α-stimulated MMP-9 up-regulation. Taken together, our data suggest that p65/c-Jun-mediated DNA looping is involved in TNF-α-induced MMP-9 up-regulation and that the recruitment of p300 or HDAC1 to NFκB and AP-1 binding sites modifies the level of DNA looping. Copyright © 2015 Elsevier B.V. All rights reserved.

Some Thoughts on Applied Geography.

ERIC Educational Resources Information Center

Gritzner, Charles F.

1979-01-01

The geography student should be offered the option of applied geography courses as well as the more conservative humanistic approach, in order to respond to the challenges presented by existing societal needs and vocational opportunities. (Author/CK)

ZN2+-INDUCED IL-8 EXPRESSION INVOLVES AP-1, JNK, AND ERK ACTIVITIES IN HUMAN AIRWAY EPITHELIAL CELLS

EPA Science Inventory

Exposure to zinc-laden particulate matter (PM) in ambient and occupational settings has been associated with proinflammatory responses in the lung. IL-8 is an important proinflammatory cytokine in the human lung and is induced in human airway epithelial cells exposed to zin...

Assessment of Combined Ascorbyl Palmitate (AP) and Sodium Ascorbyl Phosphate (SAP) on Facial Skin Sebum Control in Female Healthy Volunteers.

PubMed

Khan, H; Akhtar, N; Ali, A

2017-01-01

The skin is fortified with a setup of lipophilic and hydrophilic, enzymatic and non-enzymatic antioxidant systems. Ascorbyl palmitate (AP) and sodium ascorbyl phosphate (SAP) are reported as lipophilic and hydrophilic antioxidants, respectively used for skin care. Present study was aimed to assess the combined AP (in oil phase) and SAP (in aqueous phase) via multiple emulsion (ME 1 ) for controlling sebum secretions in healthy human females. FTIR analysis of AP and SAP was performed for identification. Multiple emulsions (ME 1 and control) were prepared and analyzed for physical stability. Antioxidant activities of AP, SAP as well as ME 1 (with combination of these compounds) were determined by DPPH method. 11 female volunteers were included in a single-blinded, placebo-controlled, split-face comparative study. Volunteers were instructed to apply ME 1 on left cheek while control (without AP and SAP) on right cheek, for a period of 90 days. A non-invasive photometric device (Sebumeter ® ) was used for the measurement of sebum secretions on both sides of the face with subsequent time intervals. A good antioxidant activity of ME 1 was observed. ME 1 treatments reduced significant facial sebum secretions as compared with control/placebo treatments. It was concluded that combined AP and SAP supplementations to skin proved a promising choice for controlling facial sebum secretions and could be evaluated for undesired oily skin and acne reductions for beautifying the facial appearance. © Georg Thieme Verlag KG Stuttgart · New York.

A novel AP92-like Crimean-Congo hemorrhagic fever virus strain, Greece.

PubMed

Papa, Anna; Chaligiannis, Ilias; Kontana, Natasa; Sourba, Tatiana; Tsioka, Katerina; Tsatsaris, Andreas; Sotiraki, Smaragda

2014-09-01

Ticks were collected from various regions of northern Greece and tested for the presence of Crimean-Congo hemorrhagic fever virus (CCHFV) RNA. Human and animal sera were collected in the regions where CCHFV-positive ticks were detected, and they were tested for the presence of IgG antibodies against the virus. A CCHFV strain was detected in Rhipicephalus bursa ticks collected from sheep in Kastoria regional unit, differing by 9.7% at the nucleotide level from the AP92 strain, which was isolated in 1975 in another region of Greece. Up to date, CCHF cases have not been reported in these regions. The human seroprevalence in the area was estimated at 6%, while IgG-positive sheep was detected in two of the four neighboring farms tested. The circulation of this specific CCHFV lineage in Greece, especially in a region where the seroprevalence is high, together with the lack of human CCHF cases, suggests a probable antigenic, but non- or low-pathogenic character of this lineage. Further studies on these strains will increase our knowledge about the role of AP92-like strains in the CCHF epidemiology, which might be useful for drug and vaccine design. Copyright © 2014 Elsevier GmbH. All rights reserved.

ATP binding cassette G1-dependent cholesterol efflux during inflammation.

PubMed

de Beer, Maria C; Ji, Ailing; Jahangiri, Anisa; Vaughan, Ashley M; de Beer, Frederick C; van der Westhuyzen, Deneys R; Webb, Nancy R

2011-02-01

ATP binding cassette transporter G1 (ABCG1) mediates the transport of cellular cholesterol to HDL, and it plays a key role in maintaining macrophage cholesterol homeostasis. During inflammation, HDL undergoes substantial remodeling, acquiring lipid changes and serum amyloid A (SAA) as a major apolipoprotein. In the current study, we investigated whether remodeling of HDL that occurs during acute inflammation impacts ABCG1-dependent efflux. Our data indicate that lipid free SAA acts similarly to apolipoprotein A-I (apoA-I) in mediating sequential efflux from ABCA1 and ABCG1. Compared with normal mouse HDL, acute phase (AP) mouse HDL containing SAA exhibited a modest but significant 17% increase in ABCG1-dependent efflux. Interestingly, AP HDL isolated from mice lacking SAA (SAAKO mice) was even more effective in promoting ABCG1 efflux. Hydrolysis with Group IIA secretory phospholipase A(2) (sPLA(2)-IIA) significantly reduced the ability of AP HDL from SAAKO mice to serve as a substrate for ABCG1-mediated cholesterol transfer, indicating that phospholipid (PL) enrichment, and not the presence of SAA, is responsible for alterations in efflux. AP human HDL, which is not PL-enriched, was somewhat less effective in mediating ABCG1-dependent efflux compared with normal human HDL. Our data indicate that inflammatory remodeling of HDL impacts ABCG1-dependent efflux independent of SAA.

Phase correlated adequate afferent action potentials as a drive of human spinal oscillators.

PubMed

Schalow, G

1993-12-01

1. By recording, with 2 pairs of wire electrodes, single-fibre action potentials (APs) from lower sacral nerve roots of a brain-dead human and a patient with spinal cord lesion, impulse patterns of afferent APs and impulse trains of oscillatory firing motoneurons could be identified and correlated. 2. Two highly activated secondary muscle spindle afferents increased and decreased their activity at about 0.3 Hz. The duration of the doublet interspike interval of a secondary spindle afferent fibre showed no correlation to the oscillation period of the motoneuron. 3. A continuously oscillatory firing motoneuron innervating the external and sphincter showed more transient breaks with the reduction of the number of phase correlated APs from 2 spindle afferents, indicating a looser oscillation. A transient brake of a 157 msec period alpha 2-oscillation could be correlated to the shift of a interspike interval distribution peak from 150 to 180 msec of the adequate afferent input, which suggests a transient loss of the necessary phase relation. 4. Oscillatory firing alpha 2-motoneurons innervating the external bladder and anal sphincters fired independently according to their phase correlated APs from the urinary bladder stretch receptor and muscle spindle afferents respectively; the bladder motoneuron slightly inhibited the anal motoneuron. 5. Receptors of the afferents and innervation sites of oscillatory firing motoneurons could be located within the urinary tract and the anal canal.