Sample records for nci mouse collective
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2012-01-19
... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request: Solar Cell: A Mobile UV Manager for Smart Phones (NCI) SUMMARY: In compliance with the... Manager for Smart Phones (NCI). Type of Information Collection Request: New. Need and Use of Information...
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Data Sets from Major NCI Initiaves
The NCI Data Catalog includes links to data collections produced by major NCI initiatives and other widely used data sets, including animal models, human tumor cell lines, epidemiology data sets, genomics data sets from TCGA, TARGET, COSMIC, GSK, NCI60.
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Wang, Jingbo; Bastrakova, Irina; Evans, Ben; Gohar, Kashif; Santana, Fabiana; Wyborn, Lesley
2015-04-01
National Computational Infrastructure (NCI) manages national environmental research data collections (10+ PB) as part of its specialized high performance data node of the Research Data Storage Infrastructure (RDSI) program. We manage 40+ data collections using NCI's Data Management Plan (DMP), which is compatible with the ISO 19100 metadata standards. We utilize ISO standards to make sure our metadata is transferable and interoperable for sharing and harvesting. The DMP is used along with metadata from the data itself, to create a hierarchy of data collection, dataset and time series catalogues that is then exposed through GeoNetwork for standard discoverability. This hierarchy catalogues are linked using a parent-child relationship. The hierarchical infrastructure of our GeoNetwork catalogues system aims to address both discoverability and in-house administrative use-cases. At NCI, we are currently improving the metadata interoperability in our catalogue by linking with standardized community vocabulary services. These emerging vocabulary services are being established to help harmonise data from different national and international scientific communities. One such vocabulary service is currently being established by the Australian National Data Services (ANDS). Data citation is another important aspect of the NCI data infrastructure, which allows tracking of data usage and infrastructure investment, encourage data sharing, and increasing trust in research that is reliant on these data collections. We incorporate the standard vocabularies into the data citation metadata so that the data citation become machine readable and semantically friendly for web-search purpose as well. By standardizing our metadata structure across our entire data corpus, we are laying the foundation to enable the application of appropriate semantic mechanisms to enhance discovery and analysis of NCI's national environmental research data information. We expect that this will further
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78 FR 53763 - Proposed Collection; 60-day Comment Request Cancer Trials Support Unit (CTSU) (NCI)
2013-08-30
... proposed data collection projects, the National Cancer Institute (NCI), National Institutes of Health (NIH), will publish periodic summaries of proposed projects to be submitted to the Office of Management and... proposed collection of information, including the validity of the methodology and assumptions used; (3...
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2011-03-15
... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request; NCI Cancer Genetics Services Directory Web-Based Application Form and Update Mailer Summary: In... Cancer Genetics Services Directory Web-based Application Form and Update Mailer. [[Page 14035
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NCI Alliance for Nanotechnology in Cancer
The NCI Alliance for Nanotechnology in Cancer funds the Cancer Nanotechnology Training Centers collectively with the NCI Cancer Training Center. Find out about the funded Centers, to date, that train our next generation of scientists in the field of Canc
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2010-08-04
... Request; the Drug Accountability Record (Form NIH 2564) (NCI) SUMMARY: In compliance with the requirement... Management and Budget (OMB) for review and approval. Proposed Collection Title: The Drug Accountability... agent accountability. In order to fulfill these requirements, a standard Investigational Drug...
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2012-01-27
... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request; Solar Cell: A Mobile UV Manager for Smart Phones (NCI) SUMMARY: In compliance with the... Manager for Smart Phones [[Page 4335
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NCI Visuals Online contains images from the collections of the National Cancer Institute's Office of Communications and Public Liaison, including general biomedical and science-related images, cancer-specific scientific and patient care-related images, and portraits of directors and staff of the National Cancer Institute.
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2011-05-17
...; Comment Request; NCI Cancer Genetics Services Directory Web-Based Application Form and Update Mailer... currently valid OMB control number. Proposed Collection: Title: NCI Cancer Genetics Services Directory Web... included in the NCI Cancer Genetics Services Directory on NCI's Cancer.gov Web site. The information...
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Soejarto, D.D.
1992-01-01
Under the funding from the United States National Cancer Institute (NCI)¹, a program was undertaken to collect plant samples in Southeast Asia to be tested for their cancer- and AIDS-arresting properties, for the period of September 1, 1986 through August 31, 1991. The program was implemented with
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NCI's Transdisciplinary High Performance Scientific Data Platform
Evans, Ben; Antony, Joseph; Bastrakova, Irina; Car, Nicholas; Cox, Simon; Druken, Kelsey; Evans, Bradley; Fraser, Ryan; Ip, Alex; Kemp, Carina; King, Edward; Minchin, Stuart; Larraondo, Pablo; Pugh, Tim; Richards, Clare; Santana, Fabiana; Smillie, Jon; Trenham, Claire; Wang, Jingbo; Wyborn, Lesley
2016-04-01
The Australian National Computational Infrastructure (NCI) manages Earth Systems data collections sourced from several domains and organisations onto a single High Performance Data (HPD) Node to further Australia's national priority research and innovation agenda. The NCI HPD Node has rapidly established its value, currently managing over 10 PBytes of datasets from collections that span a wide range of disciplines including climate, weather, environment, geoscience, geophysics, water resources and social sciences. Importantly, in order to facilitate broad user uptake, maximise reuse and enable transdisciplinary access through software and standardised interfaces, the datasets, associated information systems and processes have been incorporated into the design and operation of a unified platform that NCI has called, the National Environmental Research Data Interoperability Platform (NERDIP). The key goal of the NERDIP is to regularise data access so that it is easily discoverable, interoperable for different domains and enabled for high performance methods. It adopts and implements international standards and data conventions, and promotes scientific integrity within a high performance computing and data analysis environment. NCI has established a rich and flexible computing environment to access to this data, through the NCI supercomputer; a private cloud that supports both domain focused virtual laboratories and in-common interactive analysis interfaces; as well as remotely through scalable data services. Data collections of this importance must be managed with careful consideration of both their current use and the needs of the end-communities, as well as its future potential use, such as transitioning to more advanced software and improved methods. It is therefore critical that the data platform is both well-managed and trusted for stable production use (including transparency and reproducibility), agile enough to incorporate new technological advances and
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The mouse-human anatomy ontology mapping project.
Hayamizu, Terry F; de Coronado, Sherri; Fragoso, Gilberto; Sioutos, Nicholas; Kadin, James A; Ringwald, Martin
2012-01-01
The overall objective of the Mouse-Human Anatomy Project (MHAP) was to facilitate the mapping and harmonization of anatomical terms used for mouse and human models by Mouse Genome Informatics (MGI) and the National Cancer Institute (NCI). The anatomy resources designated for this study were the Adult Mouse Anatomy (MA) ontology and the set of anatomy concepts contained in the NCI Thesaurus (NCIt). Several methods and software tools were identified and evaluated, then used to conduct an in-depth comparative analysis of the anatomy ontologies. Matches between mouse and human anatomy terms were determined and validated, resulting in a highly curated set of mappings between the two ontologies that has been used by other resources. These mappings will enable linking of data from mouse and human. As the anatomy ontologies have been expanded and refined, the mappings have been updated accordingly. Insights are presented into the overall process of comparing and mapping between ontologies, which may prove useful for further comparative analyses and ontology mapping efforts, especially those involving anatomy ontologies. Finally, issues concerning further development of the ontologies, updates to the mapping files, and possible additional applications and significance were considered. DATABASE URL: http://obofoundry.org/cgi-bin/detail.cgi?id=ma2ncit.
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Evans, B. J. K.; Pugh, T.; Wyborn, L. A.; Porter, D.; Allen, C.; Smillie, J.; Antony, J.; Trenham, C.; Evans, B. J.; Beckett, D.; Erwin, T.; King, E.; Hodge, J.; Woodcock, R.; Fraser, R.; Lescinsky, D. T.
2014-12-01
The National Computational Infrastructure (NCI) has co-located a priority set of national data assets within a HPC research platform. This powerful in-situ computational platform has been created to help serve and analyse the massive amounts of data across the spectrum of environmental collections - in particular the climate, observational data and geoscientific domains. This paper examines the infrastructure, innovation and opportunity for this significant research platform. NCI currently manages nationally significant data collections (10+ PB) categorised as 1) earth system sciences, climate and weather model data assets and products, 2) earth and marine observations and products, 3) geosciences, 4) terrestrial ecosystem, 5) water management and hydrology, and 6) astronomy, social science and biosciences. The data is largely sourced from the NCI partners (who include the custodians of many of the national scientific records), major research communities, and collaborating overseas organisations. By co-locating these large valuable data assets, new opportunities have arisen by harmonising the data collections, making a powerful transdisciplinary research platformThe data is accessible within an integrated HPC-HPD environment - a 1.2 PFlop supercomputer (Raijin), a HPC class 3000 core OpenStack cloud system and several highly connected large scale and high-bandwidth Lustre filesystems. New scientific software, cloud-scale techniques, server-side visualisation and data services have been harnessed and integrated into the platform, so that analysis is performed seamlessly across the traditional boundaries of the underlying data domains. Characterisation of the techniques along with performance profiling ensures scalability of each software component, all of which can either be enhanced or replaced through future improvements. A Development-to-Operations (DevOps) framework has also been implemented to manage the scale of the software complexity alone. This ensures that
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NCI Holds on to Defelice Cup | Poster
NCI kept the Defelice Cup trophy this year after beating Leidos Biomedical Research, 15 to 9, at the 10th annual Ronald H. Defelice Golf Tournament held on Columbus Day. Sixteen players on each team battled it out at the yearly contractor vs. government tournament held at Rattlewood Golf Course in Mount Airy, Md. NCI leads the series 6–4. “The score was the highest NCI margin
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License Agreements | NCI Technology Transfer Center | TTC
NCI Technology Transfer Center (TTC) licenses the discoveries of NCI and nine other NIH Institutes so new technologies can be developed and commercialized, to convert them into public health benefits.
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Evans, Ben; Allen, Chris; Antony, Joseph; Bastrakova, Irina; Gohar, Kashif; Porter, David; Pugh, Tim; Santana, Fabiana; Smillie, Jon; Trenham, Claire; Wang, Jingbo; Wyborn, Lesley
2015-04-01
The National Computational Infrastructure (NCI) has established a powerful and flexible in-situ petascale computational environment to enable both high performance computing and Data-intensive Science across a wide spectrum of national environmental and earth science data collections - in particular climate, observational data and geoscientific assets. This paper examines 1) the computational environments that supports the modelling and data processing pipelines, 2) the analysis environments and methods to support data analysis, and 3) the progress so far to harmonise the underlying data collections for future interdisciplinary research across these large volume data collections. NCI has established 10+ PBytes of major national and international data collections from both the government and research sectors based on six themes: 1) weather, climate, and earth system science model simulations, 2) marine and earth observations, 3) geosciences, 4) terrestrial ecosystems, 5) water and hydrology, and 6) astronomy, social and biosciences. Collectively they span the lithosphere, crust, biosphere, hydrosphere, troposphere, and stratosphere. The data is largely sourced from NCI's partners (which include the custodians of many of the major Australian national-scale scientific collections), leading research communities, and collaborating overseas organisations. New infrastructures created at NCI mean the data collections are now accessible within an integrated High Performance Computing and Data (HPC-HPD) environment - a 1.2 PFlop supercomputer (Raijin), a HPC class 3000 core OpenStack cloud system and several highly connected large-scale high-bandwidth Lustre filesystems. The hardware was designed at inception to ensure that it would allow the layered software environment to flexibly accommodate the advancement of future data science. New approaches to software technology and data models have also had to be developed to enable access to these large and exponentially
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Displays obligations for grants, contracts, training fellowships, intramural research, and management and support, including the number of grant awards, funding amounts, and percent of the total NCI budget.
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2013-01-14
... Request (60-Day FRN): The National Cancer Institute (NCI) SmokefreeTXT (Text Message) Program Evaluation..., Behavioral Scientist/ Health Science Administrator, Division of Cancer Control and Population Sciences, 6130... text message smoking cessation intervention designed for young adult smokers ages 18-29. The Smokefree...
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Global Proteome Analysis of the NCI-60 Cell Line Panel
Directory of Open Access Journals (Sweden)
Amin Moghaddas Gholami
2013-08-01
Full Text Available The NCI-60 cell line collection is a very widely used panel for the study of cellular mechanisms of cancer in general and in vitro drug action in particular. It is a model system for the tissue types and genetic diversity of human cancers and has been extensively molecularly characterized. Here, we present a quantitative proteome and kinome profile of the NCI-60 panel covering, in total, 10,350 proteins (including 375 protein kinases and including a core cancer proteome of 5,578 proteins that were consistently quantified across all tissue types. Bioinformatic analysis revealed strong cell line clusters according to tissue type and disclosed hundreds of differentially regulated proteins representing potential biomarkers for numerous tumor properties. Integration with public transcriptome data showed considerable similarity between mRNA and protein expression. Modeling of proteome and drug-response profiles for 108 FDA-approved drugs identified known and potential protein markers for drug sensitivity and resistance. To enable community access to this unique resource, we incorporated it into a public database for comparative and integrative analysis (http://wzw.tum.de/proteomics/nci60.
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NCI collaborates with Multiple Myeloma Research Foundation
The National Cancer Institute (NCI) announced a collaboration with the Multiple Myeloma Research Foundation (MMRF) to incorporate MMRF's wealth of genomic and clinical data on the disease into the NCI Genomic Data Commons (GDC), a publicly available datab
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NIH mouse study finds gut microorganisms may determine cancer treatment outcome
An intact gut commensal microbiota, which is a population of microorganisms living in the intestine, is required for optimal response to cancer therapy, according to a mouse study by scientists at the National Cancer Institute (NCI)
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CRADA Payment Options | NCI Technology Transfer Center | TTC
NCI TTC CRADA PAYMENT OPTIONS: Electronic Payments by Wire Transfer via Fedwire, Mail a check to the Institute or Center, or Automated Clearing House (ACH)/Electronic Funds Transfer (ETF) payments via Pay.gov (NCI ONLY).
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International Fellows of NCI at Frederick | Poster
Each year, the Employee Diversity Team (EDT) acknowledges members of the NCI at Frederick Community for their achievements and contributions towards the mission of facility. Historically, the team has profiled the “Women of NCI at Frederick,” but this year, the team decided to instead shed light on the diverse and successful individuals who make up the international fellows community.
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NCI at Frederick Ebola Response Team | Poster
Editor’s note: This article was adapted from the Employee Diversity Team’s display case exhibit “Recognizing the NCI at Frederick Ebola Response Team,” in the lobby of Building 549. The Poster staff recognizes that this article does not include everyone who was involved in the response to the Ebola crisis, both at NCI at Frederick and in Africa. When the Ebola crisis broke out
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IJUE. Tema 3. Les competències de la Unió Europea
Torres Pérez, María
2018-01-01
PowerPoint del Tema 3 de la asignatura "Institucions Jurídiques de la Unió Europea". Curso académico 2017-2018. Tema 3. Les competències de la Unió Europea. 1. L’atribució de competències a la Unió Europea. 2. La delimitació de les competències a la Unió Europea. 3. Els principis que regeixen l’exercici de les competències. 4. L’exercici de les competències de la Unió per “alguns Estats membres”.
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An NCI perspective on creating sustainable biospecimen resources.
Vaught, Jimmie; Rogers, Joyce; Myers, Kimberly; Lim, Mark David; Lockhart, Nicole; Moore, Helen; Sawyer, Sherilyn; Furman, Jeffrey L; Compton, Carolyn
2011-01-01
High-quality biospecimens with appropriate clinical annotation are critical in the era of personalized medicine. It is now widely recognized that biospecimen resources need to be developed and operated under established scientific, technical, business, and ethical/legal standards. To date, such standards have not been widely practiced, resulting in variable biospecimen quality that may compromise research efforts. The National Cancer Institute (NCI) Office of Biorepositories and Biospecimen Research (OBBR) was established in 2005 to coordinate NCI's biospecimen resource activities and address those issues that affect access to the high-quality specimens and data necessary for its research enterprises as well as the broader translational research field. OBBR and the NCI Biorepository Coordinating Committee developed NCI's "Best Practices for Biospecimen Resources" after consultation with a broad array of experts. A Biospecimen Research Network was established to fund research to develop additional evidence-based practices. Although these initiatives will improve the overall availability of high-quality specimens and data for cancer research, OBBR has been authorized to implement a national biobanking effort, cancer HUman Biobank (caHUB). caHUB will address systematically the gaps in knowledge needed to improve the state-of-the-science and strengthen the standards for human biobanking. This commentary outlines the progressive efforts by NCI in technical, governance, and economic considerations that will be important as the new caHUB enterprise is undertaken.
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Mouse Xenograft Model for Mesothelioma | NCI Technology Transfer Center | TTC
The National Cancer Institute is seeking parties interested in collaborative research to co-develop, evaluate, or commercialize a new mouse model for monoclonal antibodies and immunoconjugates that target malignant mesotheliomas. Applications of the technology include models for screening compounds as potential therapeutics for mesothelioma and for studying the pathology of mesothelioma.
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The NCI Alliance for Nanotechnology in Cancer: achievement and path forward.
Ptak, Krzysztof; Farrell, Dorothy; Panaro, Nicholas J; Grodzinski, Piotr; Barker, Anna D
2010-01-01
Nanotechnology is a 'disruptive technology', which can lead to a generation of new diagnostic and therapeutic products, resulting in dramatically improved cancer outcomes. The National Cancer Institute (NCI) of National Institutes of Health explores innovative approaches to multidisciplinary research allowing for a convergence of molecular biology, oncology, physics, chemistry, and engineering and leading to the development of clinically worthy technological approaches. These initiatives include programmatic efforts to enable nanotechnology as a driver of advances in clinical oncology and cancer research, known collectively as the NCI Alliance for Nanotechnology in Cancer (ANC). Over the last 5 years, ANC has demonstrated that multidisciplinary approach catalyzes scientific developments and advances clinical translation in cancer nanotechnology. The research conducted by ANC members has improved diagnostic assays and imaging agents, leading to the development of point-of-care diagnostics, identification and validation of numerous biomarkers for novel diagnostic assays, and the development of multifunctional agents for imaging and therapy. Numerous nanotechnology-based technologies developed by ANC researchers are entering clinical trials. NCI has re-issued ANC program for next 5 years signaling that it continues to have high expectations for cancer nanotechnology's impact on clinical practice. The goals of the next phase will be to broaden access to cancer nanotechnology research through greater clinical translation and outreach to the patient and clinical communities and to support development of entirely new models of cancer care.
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DNA fingerprinting of the NCI-60 cell line panel.
Lorenzi, Philip L; Reinhold, William C; Varma, Sudhir; Hutchinson, Amy A; Pommier, Yves; Chanock, Stephen J; Weinstein, John N
2009-04-01
The National Cancer Institute's NCI-60 cell line panel, the most extensively characterized set of cells in existence and a public resource, is frequently used as a screening tool for drug discovery. Because many laboratories around the world rely on data from the NCI-60 cells, confirmation of their genetic identities represents an essential step in validating results from them. Given the consequences of cell line contamination or misidentification, quality control measures should routinely include DNA fingerprinting. We have, therefore, used standard DNA microsatellite short tandem repeats to profile the NCI-60, and the resulting DNA fingerprints are provided here as a reference. Consistent with previous reports, the fingerprints suggest that several NCI-60 lines have common origins: the melanoma lines MDA-MB-435, MDA-N, and M14; the central nervous system lines U251 and SNB-19; the ovarian lines OVCAR-8 and OVCAR-8/ADR (also called NCI/ADR); and the prostate lines DU-145, DU-145 (ATCC), and RC0.1. Those lines also show that the ability to connect two fingerprints to the same origin is not affected by stable transfection or by the development of multidrug resistance. As expected, DNA fingerprints were not able to distinguish different tissues-of-origin. The fingerprints serve principally as a barcodes.
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NCI Pediatric Preclinical Testing Consortium
NCI has awarded grants to five research teams to participate in its Pediatric Preclinical Testing Consortium, which is intended to help to prioritize which agents to pursue in pediatric clinical trials.
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2010-10-06
...; Comment Request; Drug Accountability Record (Form NIH 2564) (NCI) SUMMARY: In compliance with the..., 2011, unless it displays a valid OMB control number. Proposed Collection: Title: Drug Accountability... accountability. In order to fulfill these requirements, a standard Investigational Drug Accountability Report...
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NCI's Role in Immunotherapy Research
... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Resources for ... promising immunotherapies to the clinic more efficiently and cost effectively. For ... of the checkpoint inhibitor pembrolizumab in patients with ...
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NCI-MATCH Trial Links Targeted Drugs to Mutations
Investigators for the nationwide trial, NCI-MATCH: Molecular Analysis for Therapy Choice, announced that the trial will seek to determine whether targeted therapies for people whose tumors have specific gene mutations will be effective regardless of their cancer type. NCI-MATCH will incorporate more than 20 different study drugs or drug combinations, each targeting a specific gene mutation, in order to match each patient in the trial with a therapy that targets a molecular abnormality in their tumor.
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NCI Takes Back the Defelice Cup at Ninth Annual Golf Tournament | Poster
By Ashley DeVine, Staff Writer After being down by a point in the morning, NCI reclaimed the Defelice Cup trophy from Leidos Biomedical Research, with a final score of 12 ½ to 11 ½, at the ninth annual Ronald H. Defelice Golf Tournament, held Oct. 13. “The tightest matches in the nine-year history of this cup competition resulted in a narrow victory for NCI and allowed NCI to
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Find an NCI-Designated Cancer Center
Find the locations of NCI-designated cancer centers by area, region, state, or name that includes contact information to help health care providers and cancer patients with referrals to clinical trials.
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2010-12-23
... Request; Technology Transfer Center External Customer Satisfaction Survey (NCI) SUMMARY: In compliance...: Technology Transfer Center External Customer Satisfaction Survey (NCI). Type of Information Collection...: Obtain information on the satisfaction of TTC's external customers with TTC customer services; collect...
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DISSENYAR EXPERIÈNCIES AMB VALOR TURÍSTIC: PAISATGES URBANS
Directory of Open Access Journals (Sweden)
Francesc Fusté
2015-10-01
Full Text Available Aquest article tracta sobre les possibilitats que la creació d’experiències té en relació al desenvolupament empresarial i regional, gràcies a la tematització del sector turístic i la modificació intencional de l’entorn, tant cultural com natural. El paisatge caracteritza els espais en funció de la seva configuració territorial i també arquitectònica i urbana. Les estructures arquitectòniques, els esdeveniments i les activitats que impliquen la participació activa dels usuaris són la clau de l’èxit del disseny de les experiències amb un valor afegit, on les noves tecnologies ajuden a emfatitzar-ne l’impacte. Sigui com sigui, convertir els llocs en experiències tant pels residents com pels visitants.
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NCI Scientists Awarded National Medal of Technology and Innovation by President Obama | Poster
Two NCI scientists received the National Medal of Technology and Innovation, the nation’s highest honor for technological achievement. The award was announced by President Obama in October. The honorees, John Schiller, Ph.D., Laboratory of Cellular Oncology (LCO), Center for Cancer Research, NCI, and Douglas Lowy, M.D., also from LCO and NCI deputy director, received their medals at a White House ceremony on Nov. 20.
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Selected Publications by the NCI Director
Dr. Norman Sharpless's written work on cancer research appears in many leading scientific journals, as well as a variety of other publications. This page lists some of the articles published by Dr. Sharpless since becoming NCI director.
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Invention Development Program Helps Nurture NCI at Frederick Technologies | Poster
The Invention Development Fund (IDF) was piloted by the Technology Transfer Center (TTC) in 2014 to facilitate the commercial development of NCI technologies. The IDF received a second round of funding from the NCI Office of the Director and the Office of Budget and Management to establish the Invention Development Program (IDP) for fiscal year 2016. The IDP is using these funds to help advance a second set of inventions.
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About TTC | NCI Technology Transfer Center | TTC
The TTC facilitates licensing and co-development partnerships between biomedical industry, academia, and government agencies and the research laboratories of the NCI and nine other institutes and centers of NIH.
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Life Outside NCI | Cancer Prevention Fellowship Program
The CPFP Office is located at the NCI facilities in Rockville, Maryland, near the Nation’s Capital. With the convenient Metro subway reaching throughout the metropolitan area, transportation is within easy reach.
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At NCI, Supporting the Best Science
Yesterday, at the AACR annual meeting, Dr. Doug Lowy spoke directly to the research community about his goals as NCI Acting Director. Dr. Lowy said that he plans to continue many of the programs launched by his predecessor, Dr. Harold Varmus, and to sharp
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Robert Wiltrout Says Goodbye to NCI in 2015 | Poster
After 34 years at NCI, Robert Wiltrout, Ph.D., said he is looking forward to trading his I-270 commute for another type of commute: exploring the waterways of Maryland, Alaska, and Wyoming to fulfill his love of fishing. Wiltrout officially retired as director of the NCI Center for Cancer Research (CCR) on July 2 of last year. Throughout his college academic career, Wiltrout had an interest in science, but it was not until he was working on a research project for his master’s degree that he considered a career in scientific research.
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NCI and the Precision Medicine Initiative®
NCI's activities related to precision medicine focuses on new and expanded precision medicine clinical trials; mechanisms to overcome drug resistance to cancer treatments; and developing a shared digital repository of precision medicine trials data.
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2011-07-27
... calculations that justify the proposed sample size, the expected response rate, methods for assessing potential... Qualitative Feedback on Agency Service Delivery: National Cancer Center (NCI) ACTION: 30-Day notice of... Collection Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency...
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Evans, B. J. K.; Foster, C.; Minchin, S. A.; Pugh, T.; Lewis, A.; Wyborn, L. A.; Evans, B. J.; Uhlherr, A.
2014-12-01
The National Computational Infrastructure (NCI) has established a powerful in-situ computational environment to enable both high performance computing and data-intensive science across a wide spectrum of national environmental data collections - in particular climate, observational data and geoscientific assets. This paper examines 1) the computational environments that supports the modelling and data processing pipelines, 2) the analysis environments and methods to support data analysis, and 3) the progress in addressing harmonisation of the underlying data collections for future transdisciplinary research that enable accurate climate projections. NCI makes available 10+ PB major data collections from both the government and research sectors based on six themes: 1) weather, climate, and earth system science model simulations, 2) marine and earth observations, 3) geosciences, 4) terrestrial ecosystems, 5) water and hydrology, and 6) astronomy, social and biosciences. Collectively they span the lithosphere, crust, biosphere, hydrosphere, troposphere, and stratosphere. The data is largely sourced from NCI's partners (which include the custodians of many of the national scientific records), major research communities, and collaborating overseas organisations. The data is accessible within an integrated HPC-HPD environment - a 1.2 PFlop supercomputer (Raijin), a HPC class 3000 core OpenStack cloud system and several highly connected large scale and high-bandwidth Lustre filesystems. This computational environment supports a catalogue of integrated reusable software and workflows from earth system and ecosystem modelling, weather research, satellite and other observed data processing and analysis. To enable transdisciplinary research on this scale, data needs to be harmonised so that researchers can readily apply techniques and software across the corpus of data available and not be constrained to work within artificial disciplinary boundaries. Future challenges will
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2011-04-15
... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request; Food Reporting Comparison Study (FORCS) and Food and Eating Assessment Study (FEAST) (NCI... Collection: Title: Food Reporting Comparison Study (FORCS) and Food and Eating Assessment Study (FEAST) (NCI...
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Large-Scale Data Collection Metadata Management at the National Computation Infrastructure
Wang, J.; Evans, B. J. K.; Bastrakova, I.; Ryder, G.; Martin, J.; Duursma, D.; Gohar, K.; Mackey, T.; Paget, M.; Siddeswara, G.
2014-12-01
Data Collection management has become an essential activity at the National Computation Infrastructure (NCI) in Australia. NCI's partners (CSIRO, Bureau of Meteorology, Australian National University, and Geoscience Australia), supported by the Australian Government and Research Data Storage Infrastructure (RDSI), have established a national data resource that is co-located with high-performance computing. This paper addresses the metadata management of these data assets over their lifetime. NCI manages 36 data collections (10+ PB) categorised as earth system sciences, climate and weather model data assets and products, earth and marine observations and products, geosciences, terrestrial ecosystem, water management and hydrology, astronomy, social science and biosciences. The data is largely sourced from NCI partners, the custodians of many of the national scientific records, and major research community organisations. The data is made available in a HPC and data-intensive environment - a ~56000 core supercomputer, virtual labs on a 3000 core cloud system, and data services. By assembling these large national assets, new opportunities have arisen to harmonise the data collections, making a powerful cross-disciplinary resource.To support the overall management, a Data Management Plan (DMP) has been developed to record the workflows, procedures, the key contacts and responsibilities. The DMP has fields that can be exported to the ISO19115 schema and to the collection level catalogue of GeoNetwork. The subset or file level metadata catalogues are linked with the collection level through parent-child relationship definition using UUID. A number of tools have been developed that support interactive metadata management, bulk loading of data, and support for computational workflows or data pipelines. NCI creates persistent identifiers for each of the assets. The data collection is tracked over its lifetime, and the recognition of the data providers, data owners, data
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Researchers at the National Cancer Institute’s Laboratory of Molecular Biology (NCI LMB) have developed and isolated several single domain monoclonal human antibodies against GPC2. NCI seeks parties interested in licensing or co-developing GPC2 antibodies and/or conjugates.
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Directory of Open Access Journals (Sweden)
Ramon Riu
2010-07-01
Full Text Available La doctrina de la Sentència 31/2010 sobre la definició estatutària de les categories competencials (251-257 Mercè Barceló i SerramaleraLa doctrina del Tribunal Constitucional sobre la definició de competències. Les competències exclusives, les compartides i les executives (258-261Antoni Bayona RocamoraLa doctrina de la Sentència 31/2010 sobre les competències executives (Xavier Bernadí GilLa doctrina del Tribunal sobre la definició de les competències. Les ompetències exclusives, les compartides i les executives (270-276Marc Carrillo LópezEls efectes de la Sentència sobre la definició estatutària de les competències: la «devaluació» jurídica dels estatuts d’autonomia (277-281Mercè Corretja TorrensLes categories funcionals de competències a l’Estatut d’autonomia de Catalunya. Comentaris a la Sentència 31/2010 (282-287Ramon Riu FortunyTipologia de les competències. El seu abast funcional: els articles 110 a 112 (288-294Joaquín Tornos Massostenella e no enmendalla (262-269 La doctrina de la Sentencia 31/2010 sobre la definición estatutaria de las categorías competenciales (251-257Mercè Barceló i SerramaleraLa doctrina del Tribunal Constitucional sobre la definición de competencias. Las competencias exclusivas, las compartidas y las ejecutivas (258-261Antoni Bayona RocamoraLa doctrina de la Sentencia 31/2010 sobre las competencias ejecutivas (sostenella e no enmendalla (262-270 Xavier Bernadí GilLa doctrina del Tribunal sobre la definición de las competencias. Las competencias exclusivas, las compartidas y las ejecutivas (271-277Marc Carrillo LópezLos efectos de la Sentencia sobre la definición estatutaria de las competencias:la «devaluación» jurídica de los estatutos de autonomía (278-283Mercè Corretja TorrensLas categorías funcionales de competencias en el Estatuto de Autonomía de Cataluña. Comentarios a la Sentencia 31/2010 (284-289Ramon Riu FortunyTipología de las competencias. Su alcance
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Evans, Ben; Wyborn, Lesley; Druken, Kelsey; Richards, Clare; Trenham, Claire; Wang, Jingbo; Rozas Larraondo, Pablo; Steer, Adam; Smillie, Jon
2017-04-01
The National Computational Infrastructure (NCI) facility hosts one of Australia's largest repositories (10+ PBytes) of research data collections spanning datasets from climate, coasts, oceans, and geophysics through to astronomy, bioinformatics, and the social sciences domains. The data are obtained from national and international sources, spanning a wide range of gridded and ungridded (i.e., line surveys, point clouds) data, and raster imagery, as well as diverse coordinate reference projections and resolutions. Rather than managing these data assets as a digital library, whereby users can discover and download files to personal servers (similar to borrowing 'books' from a 'library'), NCI has built an extensive and well-integrated research data platform, the National Environmental Research Data Interoperability Platform (NERDIP, http://nci.org.au/data-collections/nerdip/). The NERDIP architecture enables programmatic access to data via standards-compliant services for high performance data analysis, and provides a flexible cloud-based environment to facilitate the next generation of transdisciplinary scientific research across all data domains. To improve use of modern scalable data infrastructures that are focused on efficient data analysis, the data organisation needs to be carefully managed including performance evaluations of projections and coordinate systems, data encoding standards and formats. A complication is that we have often found multiple domain vocabularies and ontologies are associated with equivalent datasets. It is not practical for individual dataset managers to determine which standards are best to apply to their dataset as this could impact accessibility and interoperability. Instead, they need to work with data custodians across interrelated communities and, in partnership with the data repository, the international scientific community to determine the most useful approach. For the data repository, this approach is essential to enable
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NIH and NCI grant-related changes during fiscal years 2014 and 2015
Wong, Rosemary S. L.
2015-03-01
The 2014 fiscal year (FY) continued to be a challenging one for all federal agencies despite the many Congressional strategies proposed to address the U.S. budget deficit. The Bipartisan Budget Act of 2013 passed by the House and Senate in December 2013 approved a two-year spending bill which cancelled the FY2014 and FY2015 required sequestration cuts (i.e., 4-5% National Institute of Health (NIH)/National Cancer Institute (NCI) budget reduction initiated on March 1, 2013), but extended the sequestration period through FY2023. This bill passage helped minimize any further budget reductions and resulted in a final FY2014 NIH budget of 29.9 billion and a NCI budget of 4.9 billion. Both NIH and NCI worked hard to maintain awarding the same number of NIH/NCI investigator-initiated R01 and exploratory R21 grants funded in FY2014 and similar to the level seen in FY2013 and previous years (see Tables 1 and 2). Since Congress only recently passed the 2015 spending bill in December 16, 2014, the final NIH and NCI budget appropriations for FY2015 remains unknown at this time and most likely will be similar to the FY2014 budget level. The NCI overall success and funding rates for unsolicited investigator-initiated R01 applications remained at 15%, while the success rate for exploratory R21 applications was 12% in FY2014 with similar rates seen in FY2013 (see Tables 1 and 2). The success rate for biomedical research applications in the Photodynamic Therapy and laser research field will be provided for the past few years. NIH provides numerous resources to help inform the extramural biomedical research community of new and current grant applicants about new grant policy changes and the grant submission and review processes.
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NCI International EBV-Gastric Cancer Consortium
A collaboration among NCI and extramural investigators, established by DCEG in 2006, that utilizes data and biospecimens from completed and ongoing case series and observational studies of gastric cancer to replicate and extend findings from previous studies hindered by small numbers of EBV-positive cases, and to stimulate multidisciplinary research in this area.
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Armstrong, Richard A; Gearing, Marla; Bigio, Eileen H; Cruz-Sanchez, Felix F; Duyckaerts, Charles; Mackenzie, Ian R A; Perry, Robert H; Skullerud, Kari; Yokoo, Hideaki; Cairns, Nigel J
2011-11-01
Neuronal intermediate filament inclusion disease (NIFID), a rare form of frontotemporal lobar degeneration (FTLD), is characterized neuropathologically by focal atrophy of the frontal and temporal lobes, neuronal loss, gliosis, and neuronal cytoplasmic inclusions (NCI) containing epitopes of ubiquitin and neuronal intermediate filament (IF) proteins. Recently, the 'fused in sarcoma' (FUS) protein (encoded by the FUS gene) has been shown to be a component of the inclusions of NIFID. To further characterize FUS proteinopathy in NIFID, we studied the spatial patterns of the FUS-immunoreactive NCI in frontal and temporal cortex of 10 cases. In the cerebral cortex, sectors CA1/2 of the hippocampus, and the dentate gyrus (DG), the FUS-immunoreactive NCI were frequently clustered and the clusters were regularly distributed parallel to the tissue boundary. In a proportion of cortical gyri, cluster size of the NCI approximated to those of the columns of cells was associated with the cortico-cortical projections. There were no significant differences in the frequency of different types of spatial patterns with disease duration or disease stage. Clusters of NCI in the upper and lower cortex were significantly larger using FUS compared with phosphorylated, neurofilament heavy polypeptide (NEFH) or α-internexin (INA) immunohistochemistry (IHC). We concluded: (1) FUS-immunoreactive NCI exhibit similar spatial patterns to analogous inclusions in the tauopathies and synucleinopathies, (2) clusters of FUS-immunoreactive NCI are larger than those revealed by NEFH or ΙΝΑ, and (3) the spatial patterns of the FUS-immunoreactive NCI suggest the degeneration of the cortico-cortical projections in NIFID.
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Directory of Open Access Journals (Sweden)
Prieto, M.
2016-12-01
Full Text Available The Ibero-Balearic collection of Meloidae Gyllenhal, 1810 (Coleoptera, Tenebrionoidea of the Museu de Ciències Naturals de Barcelona A commented catalogue of the Ibero-Balearic collection of Meloidae Gyllenhal, 1810 housed in the Museu de Ciències Naturals de Barcelona is presented. The studied material consists of 2,129 specimens belonging to 49 of 64 species from the Iberian peninsula and the Balearic Islands. The temporal coverage of the collection extends from the last decades of the nineteenth century to the present time. Revision, documentation, and computerization of the material have been made, resulting in 963 collection records (June 2014. For each lot, the catalogue includes the register number, geographical data, collection date, collector or origin of the collection, and number of specimens. Information about taxonomy and distribution of the species is also given. Chorological novelties are provided, extending the distribution areas for most species. The importance of the collection for the knowledge of the Ibero-Balearic fauna of Meloidae is discussed, particularly concerning the area of Catalonia (northeastern Iberian peninsula as it accounts for 60% of the records. Some rare or particularly interesting species in the collection are highlighted, as are those requiring protection measures in Spain and Catalonia. The catalogue also shows a brief gallery of photographs that includes four type specimens.
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College Graduate with NCI Internship Gains Experience, Carries Chemistry into Medicine | Poster
For Jennifer Marshall, the skills learned through an internship at the National Cancer Institute (NCI) at Frederick have prepared her for the next step of her life—medical school. Marshall, who will be attending the West Virginia University School of Medicine in the fall, spent three summers in NCI at Frederick’s Summer Internship Program expanding her love and passion for
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NCI researches identified a BK polyomavirus (BKV) virulent strain that causes chronic urinary tract infections, and the development of vaccine and therapeutic methods that would block BKV pathogenesis. The NCI Laboratory of Cellular Oncology, seek parties to license or co-develop this technology.
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The NCI Digital Divide Pilot Projects: implications for cancer education.
Kreps, Gary L; Gustafson, David; Salovey, Peter; Perocchia, Rosemarie Slevin; Wilbright, Wayne; Bright, Mary Anne; Muha, Cathy
2007-01-01
The National Cancer Institute (NCI) supported four innovative demonstration research projects, "The Digital Divide Pilot Projects," to test new strategies for disseminating health information via computer to vulnerable consumers. These projects involved active research collaborations between the NCI's Cancer Information Service (CIS) and regional cancer control researchers to field test new approaches for enhancing cancer communication in vulnerable communities. The projects were able to use computers to successfully disseminate relevant cancer information to vulnerable populations. These demonstration research projects suggested effective new strategies for using communication technologies to educate underserved populations about cancer prevention, control, and care.
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Published Research - NCI Alliance for Nanotechnology in Cancer
The NCI Alliance for Nanotechnology in Cancer has published much exciting and impactful research over the years. Find here a list of all of these listed in PubMed and others across the field of Cancer Nanotechnology.
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NCI intramural research highlighted at 2014 AACR meeting
This year’s American Association for Cancer Research meeting featured plenary talks by two NCI scientists, Steven Rosenberg, M.D., and Louis Staudt, M.D., Ph.D., that highlighted the challenges in developing varied and potentially synergistic treatments f
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2011-04-20
... (prostate, lung, colorectal, and ovary). In addition, cancer incidence, stage shift, and case survival are... Request; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) (NCI) SUMMARY: In compliance... for public comment on proposed data collection projects, the National Cancer Institute (NCI), the...
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NCI Core Open House Shines Spotlight on Supportive Science and Basic Research | Poster
The lobby of Building 549 at NCI at Frederick bustled with activity for two hours on Tuesday, May 1, as several dozen scientists and staff gathered for the NCI Core Open House. The event aimed to encourage discussion and educate visitors about the capabilities of the cores, laboratories, and facilities that offer support to NCI’s Center for Cancer Research.
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Horemans, Tessa; Kerstens, Monique; Clais, Sofie; Struijs, Karin; van den Abbeele, Pieter; Van Assche, Tim; Maes, Louis; Cos, Paul
2012-08-01
The interest in non-antibiotic therapies for Helicobacter pylori infections in man has considerably grown because increasing numbers of antibiotic-resistant strains are being reported. Intervention at the stage of bacterial attachment to the gastric mucosa could be an approach to improve the control/eradication rate of this infection. Fractions of purified milk fat globule membrane glycoproteins were tested in vitro for their cytotoxic and direct antibacterial effect. The anti-adhesive effect on H. pylori was determined first in a cell model using the mucus-producing gastric epithelial cell line NCI-N87 and next in the C57BL/6 mouse model after dosing at 400 mg/kg protein once or twice daily from day -2 to day 4 post-infection. Bacterial loads were determined by using quantitative real-time PCR and the standard plate count method. The milk fat globule membrane fractions did not show in vitro cytotoxicity, and a marginal antibacterial effect was demonstrated for defatted milk fat globule membrane at 256 μg/mL. In the anti-adhesion assay, the results varied from 56.0 ± 5.3% inhibition for 0.3% crude milk fat globule membrane to 79.3 ± 3.5% for defatted milk fat globule membrane. Quite surprisingly, in vivo administration of the same milk fat globule membrane fractions did not confirm the anti-adhesive effects and even caused an increase in bacterial load in the stomach. The promising anti-adhesion in vitro results could not be confirmed in the mouse model, even after the highest attainable exposure. It is concluded that raw or defatted milk fat globule membrane fractions do not have any prophylactic or therapeutic potential against Helicobacter infection. © 2012 Blackwell Publishing Ltd.
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NCI investment in nanotechnology: achievements and challenges for the future.
Dickherber, Anthony; Morris, Stephanie A; Grodzinski, Piotr
2015-01-01
Nanotechnology offers an exceptional and unique opportunity for developing a new generation of tools addressing persistent challenges to progress in cancer research and clinical care. The National Cancer Institute (NCI) recognizes this potential, which is why it invests roughly $150 M per year in nanobiotechnology training, research and development. By exploiting the various capacities of nanomaterials, the range of nanoscale vectors and probes potentially available suggests much is possible for precisely investigating, manipulating, and targeting the mechanisms of cancer across the full spectrum of research and clinical care. NCI has played a key role among federal R&D agencies in recognizing early the value of nanobiotechnology in medicine and committing to its development as well as providing training support for new investigators in the field. These investments have allowed many in the research community to pursue breakthrough capabilities that have already yielded broad benefits. Presented here is an overview of how NCI has made these investments with some consideration of how it will continue to work with this research community to pursue paradigm-changing innovations that offer relief from the burdens of cancer. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
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Hendriks, Hans R; Govaerts, Anne-Sophie; Fichtner, Iduna; Burtles, Sally; Westwell, Andrew D; Peters, Godefridus J
2017-07-11
The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen. Over a period of more than twenty years the EORTC-Cancer Research Campaign panel reviewed ∼2000 compounds of which 95 were selected for further evaluation. Selected compounds were stepwise developed with clear go/no go decision points using a pharmacologically directed programme. This approach eliminated quickly compounds with unsuitable pharmacological properties. A few compounds went into Phase I clinical evaluation. The lessons learned and many of the principles outlined in the paper can easily be applied to current and future drug discovery and development programmes. Changes in the review panel, restrictions regarding numbers and types of compounds tested in the NCI in vitro screen and the appearance of targeted agents led to the discontinuation of the European NCI programme in 2017 and its transformation into an academic platform of excellence for anticancer drug discovery and development within the EORTC-PAMM group. This group remains open for advice and collaboration with interested parties in the field of cancer pharmacology.
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Ultrasound imaging of the mouse pancreatic duct using lipid microbubbles
Banerjee, B.; McKeown, K. R.; Skovan, B.; Ogram, E.; Ingram, P.; Ignatenko, N.; Paine-Murrieta, G.; Witte, R.; Matsunaga, T. O.
2012-03-01
Research requiring the murine pancreatic duct to be imaged is often challenging due to the difficulty in selectively cannulating the pancreatic duct. We have successfully catheterized the pancreatic duct through the common bile duct in severe combined immune deficient (SCID) mice and imaged the pancreatic duct with gas filled lipid microbubbles that increase ultrasound imaging sensitivity due to exquisite scattering at the gas/liquid interface. A SCID mouse was euthanized by CO2, a midline abdominal incision made, the common bile duct cut at its midpoint, a 2 cm, 32 gauge tip catheter was inserted about 1 mm into the duct and tied with suture. The duodenum and pancreas were excised, removed in toto, embedded in agar and an infusion pump was used to instill normal saline or lipid-coated microbubbles (10 million / ml) into the duct. B-mode images before and after infusion of the duct with microbubbles imaged the entire pancreatic duct (~ 1 cm) with high contrast. The microbubbles were cavitated by high mechanical index (HMI) ultrasound for imaging to be repeated. Our technique of catheterization and using lipid microbubbles as a contrast agent may provide an effective, affordable technique of imaging the murine pancreatic duct; cavitation with HMI ultrasound would enable repeated imaging to be performed and clustering of targeted microbubbles to receptors on ductal cells would allow pathology to be localized accurately. This research was supported by the Experimental Mouse Shared Service of the AZ Cancer Center (Grant Number P30CA023074, NIH/NCI and the GI SPORE (NIH/NCI P50 CA95060).
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UNC Cancer Center Director to Lead NCI.
2017-08-01
President Donald Trump has selected Norman "Ned" Sharpless, MD, director of the University of North Carolina Lineberger Comprehensive Cancer Center, to lead the NCI. The news was met with widespread approval among cancer researchers, who view Sharpless as a strong communicator who can ably represent the needs of the cancer community in the face of proposed funding cuts. ©2017 American Association for Cancer Research.
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Creating Start-up Companies around NCI Inventions | Poster
By Karen Surabian, Thomas Stackhouse, and Rose Freel, Contributing Writers, and Rosemarie Truman, Guest Writer The National Cancer Institute (NCI), led by the Technology Transfer Center (TTC), the Avon Foundation, and The Center for Advancing Innovation have partnered to create a “first-of-a-kind” Breast Cancer Start-up Challenge.
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DEFF Research Database (Denmark)
Odgaard, Elvin V. P.; Prætorius, Helle; Leipziger, Jens Georg
2009-01-01
is stimulated remain elusive. Here, we investigate the phenomenon of nucleotide secretion in intact, perfused mouse medullary thick ascending limb (mTAL) and cortical collecting duct (CCD). The nucleotide secretion was monitored by a biosensor adapted to register nucleotides in the tubular outflow...
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Help NCI at Frederick “Knock Out Hunger” | Poster
NCI at Frederick is once again participating in the Feds Feed Families initiative, an annual food drive that addresses severe shortages of non-perishable items in food banks across D.C., Maryland, and Virginia during the summer months, when giving is at its lowest.
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Hsia, Te-Chun; Huang, Yi-Ping; Jiang, Yi-Wen; Chen, Hsin-Yu; Cheng, Zheng-Yu; Hsiao, Yung-Ting; Chen, Cheng-Yen; Peng, Shu-Fen; Chueh, Fu-Shin; Chou, Yu-Cheng; Chung, Jing-Gung
2018-04-01
Some lung cancer patients treated with gefitinib develop resistance to this drug resulting in unsatisfactory treatment outcomes. Phenethyl isothiocyanate (PEITC), present in our common cruciferous vegetables, exhibits anticancer activities in many human cancer cell lines. Currently, there is no available information on the possible modification of gefitinib resistance of lung cancer in vitro by PEITC. Thus, the effects of PEITC on gefitinib resistant lung cancer NCI-H460 cells were investigated in vitro. The total cell viability, apoptotic cell death, production of reactive oxygen species (ROS) and Ca 2+ , levels of mitochondria membrane potential (ΔΨ m ) and caspase-3, -8 and -9 activities were measured by flow cytometry assay. PEITC induced chromatin condensation was examined by DAPI staining. PEITC-induced cell morphological changes, decreased total viable cell number and induced apoptotic cell death in NCI-H460 and NCI-H460/G cells. PEITC decreased ROS production in NCI-H460 cells, but increased production in NCI-H460/G cells. PEITC increased Ca 2+ production, decreased the levels of ΔΨ m and increased caspase-3, -8 and -9 activities in both NCI-H460 and NCI-H460/G cells. Western blotting was used to examine the effect of apoptotic cell death associated protein expression in NCI-H460 NCI-H460/G cells after exposure to PEITC. Results showed that PEITC increased expression of cleaved caspase-3, PARP, GADD153, Endo G and pro-apoptotic protein Bax in NCI-H460/G cells. Based on these results, we suggest that PEITC induces apoptotic cell death via the caspase- and mitochondria-dependent pathway in NCI-H460/G cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Mishkin, Grace; Minasian, Lori M; Kohn, Elise C; Noone, Anne-Michelle; Temkin, Sarah M
2016-12-01
Enrollment of a representative population to cancer clinical trials ensures scientific reliability and generalizability of results. This study evaluated the similarity of patients enrolled in NCI-supported group gynecologic cancer trials to the incident US population. Accrual to NCI-sponsored ovarian, uterine, and cervical cancer treatment trials between 2003 and 2012 were examined. Race, ethnicity, age, and insurance status were compared to the analogous US patient population estimated using adjusted SEER incidence data. There were 18,913 accruals to 156 NCI-sponsored gynecologic cancer treatment trials, ovarian (56%), uterine (32%), and cervical cancers (12%). Ovarian cancer trials included the least racial, ethnic and age diversity. Black women were notably underrepresented in ovarian trials (4% versus 11%). Hispanic patients were underrepresented in ovarian and uterine trials (4% and 5% versus 18% and 19%, respectively), but not in cervical cancer trials (14 versus 11%). Elderly patients were underrepresented in each disease area, with the greatest underrepresentation seen in ovarian cancer patients over the age of 75 (7% versus 29%). Privately insured women were overrepresented among accrued ovarian cancer patients (87% versus 76%), and the uninsured were overrepresented among women with uterine or cervical cancers. These patterns did not change over time. Several notable differences were observed between the patients accrued to NCI funded trials and the incident population. Improving representation of racial and ethnic minorities and elderly patients on cancer clinical trials continues to be a challenge and priority. Copyright © 2016 Elsevier Inc. All rights reserved.
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Regular paths in SparQL: querying the NCI Thesaurus.
Detwiler, Landon T; Suciu, Dan; Brinkley, James F
2008-11-06
OWL, the Web Ontology Language, provides syntax and semantics for representing knowledge for the semantic web. Many of the constructs of OWL have a basis in the field of description logics. While the formal underpinnings of description logics have lead to a highly computable language, it has come at a cognitive cost. OWL ontologies are often unintuitive to readers lacking a strong logic background. In this work we describe GLEEN, a regular path expression library, which extends the RDF query language SparQL to support complex path expressions over OWL and other RDF-based ontologies. We illustrate the utility of GLEEN by showing how it can be used in a query-based approach to defining simpler, more intuitive views of OWL ontologies. In particular we show how relatively simple GLEEN-enhanced SparQL queries can create views of the OWL version of the NCI Thesaurus that match the views generated by the web-based NCI browser.
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Thornburg, Christopher C; Britt, John R; Evans, Jason R; Akee, Rhone K; Whitt, James A; Trinh, Spencer K; Harris, Matthew J; Thompson, Jerell R; Ewing, Teresa L; Shipley, Suzanne M; Grothaus, Paul G; Newman, David J; Schneider, Joel P; Grkovic, Tanja; O'Keefe, Barry R
2018-06-13
The US National Cancer Institute's (NCI) Natural Product Repository is one of the world's largest, most diverse collections of natural products containing over 230,000 unique extracts derived from plant, marine, and microbial organisms that have been collected from biodiverse regions throughout the world. Importantly, this national resource is available to the research community for the screening of extracts and the isolation of bioactive natural products. However, despite the success of natural products in drug discovery, compatibility issues that make extracts challenging for liquid handling systems, extended timelines that complicate natural product-based drug discovery efforts and the presence of pan-assay interfering compounds have reduced enthusiasm for the high-throughput screening (HTS) of crude natural product extract libraries in targeted assay systems. To address these limitations, the NCI Program for Natural Product Discovery (NPNPD), a newly launched, national program to advance natural product discovery technologies and facilitate the discovery of structurally defined, validated lead molecules ready for translation will create a prefractionated library from over 125,000 natural product extracts with the aim of producing a publicly-accessible, HTS-amenable library of >1,000,000 fractions. This library, representing perhaps the largest accumulation of natural-product based fractions in the world, will be made available free of charge in 384-well plates for screening against all disease states in an effort to reinvigorate natural product-based drug discovery.
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Gardasil® and Cervarix® | NCI Technology Transfer Center | TTC
Vaccine for human papilloma virus (HPV) to protect from cancers Key elements of the technology for Gardasil® and Cervarix originated from the HPV research of the laboratory of Drs. Douglas Lowy and John Schiller of the NCI.
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Directory of Open Access Journals (Sweden)
Lingling Tang
2018-02-01
Full Text Available Lung squamous cell carcinoma (LSCC is a common histological lung cancer subtype, but unlike lung adenocarcinoma, limited therapeutic options are available for treatment. Curcumin, a natural compound, may have anticancer effects in various cancer cells, but how it may be used to treat LSCC has not been well studied. Here, we applied curcumin to a human NCI-H292 LSCC cell line to test anticancer effects and explored underlying potential mechanisms of action. Curcumin treatment inhibited NCI-H292 cell growth and increased FOXA2 expression in a time-dependent manner. FOXA2 expression was decreased in LSCC tissues compared with adjacent normal tissues and knockdown of FOXA2 increased NCI-H292 cells proliferation. Inhibition of cell proliferation by curcumin was attenuated by FOXA2 knockdown. Moreover inhibition of STAT3 pathways by curcumin increased FOXA2 expression in NCI-H292 cells whereas a STAT3 activator (IL-6 significantly inhibited curcumin-induced FOXA2 expression. Also, SOCS1 and SOCS3, negative regulators of STAT3 activity, were upregulated by curcumin treatment. Thus, curcumin inhibited human NCI-H292 cells growth by increasing FOXA2 expression via regulation of STAT3 signaling pathways.
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DEFF Research Database (Denmark)
Lagkouvardos, Ilias; Pukall, Rüdiger; Abt, Birte
2016-01-01
of intestinal microbiomes and their interactions with diet and host. It is thus important to study in detail the diversity and functions of gut microbiota members, including those colonizing the mouse intestine. To address these issues, we aimed at establishing the Mouse Intestinal Bacterial Collection (mi...
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78 FR 46930 - Proposed Collection; Comment Request
2013-08-02
... collection instruments, please write to Headquarters, U.S. Army Training and Doctrine Command, Learning Integration, Institute for NCO Professional Development (ATCG-NCI), ATTN: Jeffery J. Colimon, 950 Jefferson... Civilian employees and Soldiers. Departing Soldiers or DA Civilian employees complete the DA Form 5434...
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How You Can Partner with NIH | NCI Technology Transfer Center | TTC
NCI Technology Transfer Center (TTC) provides an array of agreements to support the National Cancer Institute's partnering. Deciding which type of agreement to use can be a challenge: CRADA, MTA, collaboration, agreement, CTA, Materials-CRADA
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History of the Diet History Questionnaire (DHQ) | EGRP/DCCPS/NCI/NIH
Learn about the evolution of the Diet History Questionnaire (DHQ), developed by the National Cancer Institute (NCI) initially in 2001, to the DHQ II in 2010, up to the present version, DHQ III, launched in 2018.
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Russian delegation visits NIH and NCI to discuss research collaboration
The NCI Center for Global Health hosted a delegation from the Russian Foundation for Basic Research to discuss ongoing and future collaborations in cancer research. The delegation was accompanied by representatives from the US Embassy in Moscow and the Embassy of the Russian Federation in Washington DC.
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NIH Employee Invention Report (EIR) | NCI Technology Transfer Center | TTC
NIH researchers must immediately contact their Laboratory or Branch Chief and inform him or her of a possible invention, and then consult with your NCI TTC Technology Transfer Manager about submitting an Employee Invention Report (EIR) Form. | [google6f4cd5334ac394ab.html
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CellMiner: a relational database and query tool for the NCI-60 cancer cell lines
Directory of Open Access Journals (Sweden)
Reinhold William C
2009-06-01
Full Text Available Abstract Background Advances in the high-throughput omic technologies have made it possible to profile cells in a large number of ways at the DNA, RNA, protein, chromosomal, functional, and pharmacological levels. A persistent problem is that some classes of molecular data are labeled with gene identifiers, others with transcript or protein identifiers, and still others with chromosomal locations. What has lagged behind is the ability to integrate the resulting data to uncover complex relationships and patterns. Those issues are reflected in full form by molecular profile data on the panel of 60 diverse human cancer cell lines (the NCI-60 used since 1990 by the U.S. National Cancer Institute to screen compounds for anticancer activity. To our knowledge, CellMiner is the first online database resource for integration of the diverse molecular types of NCI-60 and related meta data. Description CellMiner enables scientists to perform advanced querying of molecular information on NCI-60 (and additional types through a single web interface. CellMiner is a freely available tool that organizes and stores raw and normalized data that represent multiple types of molecular characterizations at the DNA, RNA, protein, and pharmacological levels. Annotations for each project, along with associated metadata on the samples and datasets, are stored in a MySQL database and linked to the molecular profile data. Data can be queried and downloaded along with comprehensive information on experimental and analytic methods for each data set. A Data Intersection tool allows selection of a list of genes (proteins in common between two or more data sets and outputs the data for those genes (proteins in the respective sets. In addition to its role as an integrative resource for the NCI-60, the CellMiner package also serves as a shell for incorporation of molecular profile data on other cell or tissue sample types. Conclusion CellMiner is a relational database tool for
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Like a Good Neighbor, NCI-Frederick Is There | Poster
The main campus of the National Cancer Institute at Frederick is an island of sorts: 68 acres of land that was once part of Fort Detrick. Accessing NCI property means passing through the Fort Detrick gates and crossing the post. While the campus is surrounded by the military installation, is protected by NIH police, and doesn’t allow the use of tobacco products, it is not a
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NCI designated cancer center funding not influenced by organizational structure.
Wolfe, Margaret E; Yagoda, Daniel; Thurman, Paul W; Luna, Jorge M; Figg, William Douglas
2009-05-01
National Cancer Institutes (NCI) designated cancer centers use one of three organizational structures. The hypothesis of this study is that there are differences in the amount of annual NCI funding per faculty member based on a cancer center's organizational structure. The study also considers the impact of secondary factors (i.e., the existence of a clinical program, the region and the size of the city in which the cancer center is located) on funding and the number of Howard Hughes Medical Institute (HHMI) investigators at each cancer center. Of the 63 cancer centers, 44 use a matrix structure, 16 have a freestanding structure, and three have a Department of Oncology structure. Kruskal-Wallis tests reveal no statistically significant differences in the amount of funding per faculty member or the number of HHMI investigators between centers with a matrix, freestanding or Department of Oncology structure. Online research and telephone interviews with each cancer center were used to gather information, including: organizational structure, the presence of a clinical program, the number of faculty members, and the number of Howard Hughes Medical Institute investigators. Statistical tests were used to assess the impact which organizational structure has on the amount of funding per faculty member and number of HHMI investigators. While the results seem to suggest that the organizational structure of a given cancer center does not impact the amount of NCI funding or number of HHMI investigators which it attracts, the existence of this relationship is likely masked by the small sample size in this study. Further studies may be appropriate to examine the effect organizational structure has on other measurements which are relevant to cancer centers, such as quality and quantity of research produced.
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Investigation of internalization and cytotoxicity of 125I-[Tyr3]-octreotide in NCI-H446 cell line
International Nuclear Information System (INIS)
Sun Junjie; Fan Wo; Xu Yujie; Zhang Youjiu; Zhu Ran; Hu Mingjiang
2004-01-01
Objective: To investigate the [Tyr 3 ]-octreotide (TOC) internalizing capacity of NCI-H446 cell line, and the cytotoxicity of 125 I-TOC in NCI-H446 cell line. To assess the therapeutic radiopharmaceutical potentiality of 125 I-TOC for the somatostatin receptor (SSTR) positive tumor. Methods: NCI-H446 cells were incubated together with 125 I-TOC for different periods of time, the amount of internalized 125 I-TOC and the 125 I-TOC bound on the cellular nucleus were detected with γ counter, respectively. The viability of the cells was analyzed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay at different time points with various doses of 125 I-TOC, free 125 I and TOC. Results: 125 I-TOC was internalized into the nucleus and bound on the nucleus in a time-dependent manner. 125 I-TOC bound on the nucleus increased to the highest level at 24 h, the amount of nucleus bound 125 I-TOC at 24 h was 7 times higher than that at 0.5 h. Cytotoxicity of 125 I-TOC in SSTR positive NCI-H446 cells was also dose- and time-dependent. The supreme effect of cytotoxicity was found at 96 h with 74 kBq 125 I-TOC, the survival ratio of cells was reduced to (44.8 ± 7.2)%. Conclusions: 125 I-TOC can be internalized into SSTR positive cells mediated by SSTR. The NCI-H446 cells can be killed by Auger electron emitting from 125 I-TOC. Effect of cytotoxicity showed dose- and time-dependent
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The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) is pleased to announce that teams led by Jaewoo Kang (Korea University), and Yuanfang Guan with Hongyang Li (University of Michigan) as the best performers of the NCI-CPTAC DREAM Proteogenomics Computational Challenge. Over 500 participants from 20 countries registered for the Challenge, which offered $25,000 in cash awards contributed by the NVIDIA Foundation through its Compute the Cure initiative.
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Uga, Minako; Saito, Toshiyuki; Sano, Toshifumi; Yokota, Hidenori; Oguro, Keiji; Rizki, Edmi Edison; Mizutani, Tsutomu; Katura, Takusige; Dan, Ippeita; Watanabe, Eiju
2014-05-01
Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals. Although direct cortical monitoring with fNIRS has been pursued, a high-resolution visualization of hemodynamic changes associated with sensory, motor and cognitive neural responses directly from the cortical surface has yet to be realized. To acquire robust information on the hemodynamics of the cortex, devoid of signal complications in transcranial measurement, we devised a functional near-infrared cortical imaging (fNCI) technique. Here we demonstrate the first direct functional measurement of temporal and spatial patterns of cortical hemodynamics using the fNCI technique. For fNCI, inter-optode distance was set at 5mm, and light leakage from illuminators was prevented by a special optode holder made of a light-shielding rubber sheet. fNCI successfully detected the somatotopy of pig nostril sensation, as assessed in comparison with concurrent and sequential somatosensory-evoked potential (SEP) measurements on the same stimulation sites. Accordingly, the fNCI system realized a direct cortical hemodynamic measurement with a spatial resolution comparable to that of SEP mapping on the rostral region of the pig brain. This study provides an important initial step toward realizing functional cortical hemodynamic monitoring during neurosurgery of human brains. Copyright © 2014. Published by Elsevier Inc.
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NCI and the Chinese Academy of Medical Sciences Sign Statement of Intent
Today the National Cancer Institute (NCI) and the Cancer Institute/Hospital of the Chinese Academy of Medical Sciences (CICAMS) signed a statement of intent to share an interest in fostering collaborative biomedical research in oncology and a common goal
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Directory of Open Access Journals (Sweden)
Jordan Clark
2009-01-01
Full Text Available The collecting duct (CD expresses considerable amounts of PPARδ. While its role is unknown in the CD, in other renal cells it has been shown to regulate both growth and apoptosis. We thus hypothesized that PPARδ reduces apoptotic responses and stimulates cell growth in the mouse CD, and examined the effect of GW501516, a synthetic PPARδ ligand, on these responses in mouse IMCD-K2 cells. High doses of GW501516 decreased both DNA and protein synthesis in these cells by 80%, but had no overall effect on cell viability. Although anisomycin treatment resulted in an increase of caspase-3 levels of about 2.59-fold of control, GW501516 did not affect anisomycin-induced changes in active caspase-3 levels. These results show that a PPARδ ligand inhibits growth but does not affect anisomycin-apoptosis in a mouse IMCD cell line. This could have therapeutic implications for renal diseases associated with increased CD growth responses.
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Ressonàncies en plasmons sobre grafè
Alcaraz Iranzo, David
2014-01-01
Treball final de màster oficial fet en col·laboració amb Universitat Autònoma de Barcelona (UAB), Universitat de Barcelona (UB) i Institut de Ciències Fotòniques (ICFO) [ANGLÈS] Graphene is used as a novel, versatile plasmonic material. The most common way to implement resonant light-plasmon coupling is to etch graphene into periodic nanostructures, which is invasive. Here, we study a non-invasive way to engineer graphene plasmon resonances, based on periodic doping profiles. The plasmon r...
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Craig Reynolds, Ph.D., to Retire as NCI Associate Director for Frederick | Poster
On December 2, Craig Reynolds, Ph.D., director, Office of Scientific Operations, and NCI associate director for Frederick, will put the finishing touches on a 37-year career with the National Cancer Institute.
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New Phone System Coming to NCI Campus at Frederick | Poster
By Travis Fouche and Trent McKee, Guest Writers Beginning in September, phones at the NCI Campus at Frederick will begin to be replaced, as the project to upgrade the current phone system ramps up. Over the next 16 months, the Information Systems Program (ISP) will be working with Facilities Maintenance and Engineering and Computer & Statistical Services to replace the current
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The gold standard of care for hepatocellular carcinoma patients with intermediate- to locally advanced tumors is transcatheter arterial chemoembolization (TACE), a procedure whereby the tumor is targeted both with local chemotherapy and restriction of local blood supply. NCI scientists have identified a 14-gene signature predictive of response to TACE, and NCI seeks licensees or co-development partners to develop the technology toward commercialization.
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It’s Easy to Recycle at NCI at Frederick | Poster
From 2013 through the first quarter of 2018, NCI at Frederick has recycled over 1,667 tons of material, while incinerating or landfilling over 4,273 tons of trash. This earns us a recycling rate close to 28 percent, which is below the national average of 32 percent, according to the Environmental Protection Agency, and well below our goal of 50 percent. (These numbers only
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Analysis of 125I-[Tyr3] octreotide receptors of NCI-H466 cell line
International Nuclear Information System (INIS)
Sun Junjie; Fan Wo; Xu Yujie; Zhang Youjiu; Zhu Ran
2002-01-01
Objective: To study the affinity of small cell lung carcinoma to [Tyr 3 ] octreotide (TOC). Methods: Taking 125 I-[Tyr 3 ] octreotide (labeled by chloramine-T method), as the ligand, small cell lung carcinoma NCI-H466 cell line was inspected for the receptor-binding points and affinity constant. Results: The radio-chemical purity of 125 I-TOC purified through sephadex G-10 was higher than 95%. Receptor analysis study showed that the expression of somatostatin receptors on NCI-H446 cells was numerous (Bmax = 1.17 x 10 5 /cell) with strong affinity to 125 I-TOC (Kd = 0.56 nM). Conclusion: Labeled TOC could be used for small cell lung carcinoma receptor imaging and radio-pharmaceutical therapy
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Directory of Open Access Journals (Sweden)
Karina Angélica Villegas Sandoval
2017-01-01
Full Text Available L’article té com a finalitat descriure i analitzar les metodologies d'investigació utilitzades per estudis recents que aborden el tema de l’avaluació per competències a l’educació superior i la formació docent, per tal de detectar les tendències en el disseny metodològic i orientar futurs projectes d'investigació sobre aquest tema. El mètode de treball que s'ha seguit per dur a terme aquest estudi és l’anàlisi de contingut de 22 documents trobats a Dialnet. Els resultats mostren que les investigacions que tracten el tema assenyalat han anat en augment en els últims tretze anys, i es destaca el canvi de metodologia utilitzada, amb dissenys majoritàriament descriptius i avaluatius. Al seu torn, però, crida l'atenció que un gran nombre d'estudis no expliquen ni el mètode ni el disseny d'investigació que han aplicat. Es conclou que és important que les investigacions presentin un apartat que al·ludeixi al disseny metodològic a fi d’afavorir la comprensió del lector dels processos d'indagació que s'han dut a terme.
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2013-06-28
... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; 60-Day Comment Request; Family Life, Activity, Sun, Health, and Eating (FLASHE) Study (NCI) Summary: In.... Proposed Collection: Family Life, Activity, Sun, Health, and Eating (FLASHE) Study 0925--NEW, National...
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Program Spotlight: Ground Broken for NCI-supported Cancer Treatment Center in Puerto Rico
Dr. Sanya A. Springfield represented NCI at the groundbreaking ceremonies for the University of Puerto Rico (UPR) cancer hospital. In her remarks, she acknowledged the driving force behind this development is the UPR and the MD Anderson Cancer Center partnership.
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Softball Games Bring NCI and Leidos Biomed Employees Together | Poster
NCI and Leidos Biomed employees took to the fields at Nallin Pond for the third annual slow-pitch softball games on August 26. The series attracted 54 employees who were divided into four teams, Red, Blue, Gray, and White, and they were cheered on by about 40 enthusiastic spectators. In the first set of games, the Gray team defeated the Blue team, 15–8, and the White team
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Vaccines for HIV | NCI Technology Transfer Center | TTC
The development of an effective HIV vaccine has been an ongoing area of research. The high variability in HIV-1 virus strains has represented a major challenge in successful development. Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV. Two major hurdles to overcome are immunodominance and sequence diversity. This vaccine utilizes a strategy for overcoming these two issues by identifying the conserved regions of the virus and exploiting them for use in a targeted therapy. NCI seeks licensees and/or research collaborators to commercialize this technology, which has been validated in macaque models.
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NCI and the Chinese National Cancer Center pursue new collaborations in cancer research
CGH Director, Dr. Ted Trimble, and East Asia Program Director, Dr. Ann Chao, traveled to Beijing with Mr. Matthew Brown from the Department of Health and Human Services Office of Global Affairs to attend the Joint Meeting of the NCC and the U.S. NCI.
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Ratio Based Biomarkers for the Prediction of Cancer Survival | NCI Technology Transfer Center | TTC
The NCI seeks licensees or co-development partners for this technology, which describes compositions, methods and kits for identifying, characterizing biomolecules expressed in a sample that are associated with the presence, the development, or progression of cancer.
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Anàlisi forense d'evidències digitals
Bonachera López, Esteban
2014-01-01
L'objectiu principal d'aquest projecte consisteix en la realització de l'anàlisi forense del disc dur i de la memòria RAM d'un ordinador personal, en concret un Netbook, vinculat a una possible conducta delictiva. També s'inclou en l'anàlisi una base de dades del conegut programari WhatsApp extreta d'un smartphone. Per realitzar aquesta tasca s'utilitzaran eines específiques per localitzar les evidències digitals que puguin demostrar els presumptes delictes. El objetivo principal de este p...
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Mission & Role | NCI Technology Transfer Center | TTC
The NCI TTC serves as the focal point for implementing the Federal Technology Transfer Act to utilize patents as incentive for commercial development of technologies and to establish research collaborations and licensing among academia, federal laboratories, non-profit organizations, and industry. The TTC supports technology development activities for the National Cancer Institute and nine other NIH Institutes and Centers. TTC staff negotiate co-development agreements and licenses with universities, non-profit organizations, and pharmaceutical and biotechnology companies to ensure compliance with Federal statutes, regulations and the policies of the National Institutes of Health. TTC also reviews employee invention reports and makes recommendations concerning filing of domestic and foreign patent applications. | [google6f4cd5334ac394ab.html
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NCI at Frederick Employees Receive Awards at the Spring Research Festival | Poster
NCI and Frederick National Laboratory staff members were among those honored at the Spring Research Festival Awards Ceremony on May 28. The ceremony was the culmination of the festival, which was sponsored by the National Interagency Confederation for Biological Research (NICBR), May 4–7. Maj. Gen. Brian Lein, commanding general, U.S. Army Medical Research and Materiel Command
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The NCI Radiation Oncology Branch and the NHLBI Laboratory of Single Molecule Biophysics seek parties to co-develop fluorescent nanodiamonds for use as in vivo and in vitro optical tracking probes toward commercialization.
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Directory of Open Access Journals (Sweden)
Yuen Fei Wong
2011-02-01
Full Text Available Retinoic acid is the bioactive derivative of vitamin A, which plays an indispensible role in kidney development by activating retinoic acid receptors. Although the location, concentration and roles of endogenous retinoic acid in post-natal kidneys are poorly defined, there is accumulating evidence linking post-natal vitamin A deficiency to impaired renal concentrating and acidifying capacity associated with increased susceptibility to urolithiasis, renal inflammation and scarring. The aim of this study is to examine the presence and the detailed localization of endogenous retinoic acid activity in neonatal, young and adult mouse kidneys, to establish a fundamental ground for further research into potential target genes, as well as physiological and pathophysiological roles of endogenous retinoic acid in the post-natal kidneys.RARE-hsp68-lacZ transgenic mice were employed as a reporter for endogenous retinoic acid activity that was determined by X-gal assay and immunostaining of the reporter gene product, β-galactosidase. Double immunostaining was performed for β-galactosidase and markers of kidney tubules to localize retinoic acid activity. Distinct pattern of retinoic acid activity was observed in kidneys, which is higher in neonatal and 1- to 3-week-old mice than that in 5- and 8-week-old mice. The activity was present specifically in the principal cells and the intercalated cells of the collecting duct system in all age groups, but was absent from the glomeruli, proximal tubules, thin limbs of Henle's loop and distal tubules.Endogenous retinoic acid activity exists in principal cells and intercalated cells of the mouse collecting duct system after birth and persists into adulthood. This observation provides novel insights into potential roles for endogenous retinoic acid beyond nephrogenesis and warrants further studies to investigate target genes and functions of endogenous retinoic acid in the kidney after birth, particularly in the
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Simon, Steven L.
2012-01-01
The U.S. National Cancer Institute (NCI, National Institutes of Health) was requested by the U.S. Congress in 2004 to assess the number of radiation-related illnesses to be expected among the people of the Marshall Islands from nuclear tests conducted there during 1946-1958. A thorough analysis conducted by the NCI concluded that 20 of the 66 nuclear devices tested in or near the Marshall Islands resulted in measurable fallout deposition on one or more of the inhabited atolls of the Marshall ...
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Paracytosis of Haemophilus influenzae through cell layers of NCI-H292 lung epithelial cells
van Schilfgaarde, M.; van Alphen, L.; Eijk, P.; Everts, V.; Dankert, J.
1995-01-01
Haemophilus influenzae penetrates the respiratory epithelium during carriage and invasive disease, including respiratory tract infections. We developed an in vitro model system consisting of lung epithelial NCI-H292 cells on permeable supports to study the passage of H. influenzae through lung
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In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 9, 2012.
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Microsoft Office 365 Deployment Continues through June at NCI at Frederick | Poster
The latest Microsoft suite, Office 365 (O365), is being deployed to all NCI at Frederick computers during the months of May and June to comply with federal mandates. The suite includes the latest versions of Word, Excel, Outlook, PowerPoint, and Skype for Business, along with cloud-based capabilities. These cloud-based capabilities will help meet the federal mandates that
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The Puerto Rico NCI Community Oncology Research Program (PRNCORP) will be the principal organization in the island that promotes cancer prevention, control and screening/post-treatment surveillance clinical trials. It will conduct cancer care delivery research and will provide access to treatment and imaging clinical trials conducted under the reorganization of the National
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2013-05-07
... Comment Request: Financial Sustainability of Human Tissue Biobanking (NCI) Summary: In compliance with the... techniques or other forms of information technology. To Submit Comments and for Further Information: To... this publication. Proposed Collection: Financial Sustainability of Human Tissue Biobanking, 0925-NEW...
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Directory of Open Access Journals (Sweden)
Allison A. Atnip
2017-02-01
Full Text Available Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87 has been used to study the behavior of anthocyanins at a pH range of 3.0–7.4. This work examines the effects of time (0–3 h, concentration (50–1500 µM, and pH (3.0, 5.0, 7.4 on the transport and uptake of anthocyanins using NCI-N87 cells. Anthocyanins were transported from the apical to basolateral side of NCI-N87 cells in time and dose dependent manners. Over the treatment time of 3 h the rate of transport increased, especially with higher anthocyanin concentrations. The non-linear rate of transport may suggest an active mechanism for the transport of anthocyanins across the NCI-N87 monolayer. At apical pH 3.0, higher anthocyanin transport was observed compared to pH 5.0 and 7.4. Reduced transport of anthocyanins was found to occur at apical pH 5.0.
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In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 11, 2014.
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Hull, L C; Farrell, D; Grodzinski, P
2014-01-01
Although the incidence of cancer and cancer related deaths in the United States has decreased over the past two decades due to improvements in early detection and treatment, cancer still is responsible for a quarter of the deaths in this country. There is much room for improvement on the standard treatments currently available and the National Cancer Institute (NCI) has recognized the potential for nanotechnology and nanomaterials in this area. The NCI Alliance for Nanotechnology in Cancer was formed in 2004 to support multidisciplinary researchers in the application of nanotechnology to cancer diagnosis and treatment. The researchers in the Alliance have been productive in generating innovative solutions to some of the central issues of cancer treatment including how to detect tumors earlier, how to target cancer cells specifically, and how to improve the therapeutic index of existing chemotherapies and radiotherapy treatments. Highly creative ideas are being pursued where novelty in nanomaterial development enables new modalities of detection or therapy. This review highlights some of the innovative materials approaches being pursued by researchers funded by the NCI Alliance. Their discoveries to improve the functionality of nanoparticles for medical applications includes the generation of new platforms, improvements in the manufacturing of nanoparticles and determining the underlying reasons for the movement of nanoparticles in the blood. © 2013.
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NCI Think Tank Concerning the Identifiability of Biospecimens and “-Omic” Data
Weil, Carol J.; Mechanic, Leah E.; Green, Tiffany; Kinsinger, Christopher; Lockhart, Nicole C.; Nelson, Stefanie A.; Rodriguez, Laura L.; Buccini, Laura D.
2013-01-01
On June 11 and 12, 2012, the National Cancer Institute (NCI) hosted a think tank concerning the identifiability of biospecimens and “omic” Data in order to explore challenges surrounding this complex and multifaceted topic. The think tank brought together forty-six leaders from several fields, including cancer genomics, bioinformatics, human subject protection, patient advocacy, and commercial genetics. The first day involved presentations regarding the state of the science of re-identificati...
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Researchers at the National Cancer Institute (NCI) RNA Biology Laboratory have developed nanoparticles that can deliver an agent (i.e., therapeutic or imaging) and release the agent upon targeted photoactivation allowing for controlled temporal and localized release of the agent.
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Test de visualitat: les preferències del bon disseny
Directory of Open Access Journals (Sweden)
Quim Merino
2014-07-01
Full Text Available Aquest article pretén donar notícia de la investigació dirigida pel Grup de Recerca en Publicitat i Relacions Públiques (en endavant, GRP de la Universitat Autònoma de Barcelona duta a terme pels autors d'aquesta ressenya. El treball s'emmarca en una activitat de l'assignatura de Disseny en Publicitat i Relacions Públiques del Grau en Publicitat i Relacions Públiques de la UAB. L'objectiu del treball és constatar les preferències del consumidor davant diferents estímuls formals del disseny gràfic en publicitat
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NCIP has migrated 132 repositories from the NCI subversion repository to our public NCIP GitHub channel with the goal of facilitating third party contributions to the existing code base. Within the GitHub environment, we are advocating use of the GitHub “fork and pull” model.
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2011-02-04
... is displayed in the table below. There are no Capital Costs, Operating Costs, and/or Maintenance Costs to report. Average time Type of respondents Number of Frequency of per response Annual hour... Diet and Health Study (NCI). Type of Information Collection Request: Extension. Need and Use of...
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2013-05-23
..., mechanical, or other technological collection techniques or other forms of information technology. To Submit... purposes (e.g., an application) or to monitor or improve a program. These ICs may involve little if any... and comments to this request. Along with the analysis, NCI's ongoing education and outreach effort has...
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The national cancer institute (NCI) and cancer biology in a 'post genome world'
International Nuclear Information System (INIS)
Klausner, Richard D.
1996-01-01
The National Cancer Institute (NCI) exists to reduce the burden of all cancers through research and discovery. Extensive restructuring of the NCI over the past year has been aimed at assuring that the institution functions in all ways to promote opportunities for discovery in the laboratory, in the clinic, and in the community. To do this well requires the difficult and almost paradoxical problem of planning for scientific discovery which, in turn is based on the freedom to pursue the unanticipated. The intellectual and structural landscape of science is changing and it places new challenges, new demands and new opportunities for facilitating discovery. The nature of cancer as a disease of genomic instability and of accumulated genetic change, coupled with a possibility of the development of new technologies for reading, utilizing, interpreting and manipulating the genome of single cells, provides unprecedented opportunities for a new type of high through-put biology that will change the nature of discovery, cancer detection, diagnosis, prognosis, therapeutic decision-making and therapeutic discovery. To capture these new opportunities will require attention to be paid to integrate the development of technology and new scientific discoveries with the ability to apply advances rapidly and efficiently through clinical trials
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Directory of Open Access Journals (Sweden)
Rivka Colen
2014-10-01
Full Text Available The National Cancer Institute (NCI Cancer Imaging Program organized two related workshops on June 26–27, 2013, entitled “Correlating Imaging Phenotypes with Genomics Signatures Research” and “Scalable Computational Resources as Required for Imaging-Genomics Decision Support Systems.” The first workshop focused on clinical and scientific requirements, exploring our knowledge of phenotypic characteristics of cancer biological properties to determine whether the field is sufficiently advanced to correlate with imaging phenotypes that underpin genomics and clinical outcomes, and exploring new scientific methods to extract phenotypic features from medical images and relate them to genomics analyses. The second workshop focused on computational methods that explore informatics and computational requirements to extract phenotypic features from medical images and relate them to genomics analyses and improve the accessibility and speed of dissemination of existing NIH resources. These workshops linked clinical and scientific requirements of currently known phenotypic and genotypic cancer biology characteristics with imaging phenotypes that underpin genomics and clinical outcomes. The group generated a set of recommendations to NCI leadership and the research community that encourage and support development of the emerging radiogenomics research field to address short-and longer-term goals in cancer research.
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An NCI-FDA Interagency Oncology Task Force (IOTF) Molecular Diagnostics Workshop was held on October 30, 2008 in Cambridge, MA, to discuss requirements for analytical validation of protein-based multiplex technologies in the context of its intended use. This workshop developed through NCI's Clinical Proteomic Technologies for Cancer initiative and the FDA focused on technology-specific analytical validation processes to be addressed prior to use in clinical settings. In making this workshop unique, a case study approach was used to discuss issues related to
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NCI Statement on the U.S. Surgeon General's "Call to Action to Prevent Skin Cancer"
As the Federal Government's principal agency for cancer research and training, the National Cancer Institute (NCI) endorses the U.S. Surgeon General’s “Call to Action to Prevent Skin Cancer,” which provides a comprehensive evaluation of the current state of skin cancer prevention efforts in the United States and recommends actions for improvement in the future.
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L’avaluació de competències a l’Educació Superior: el cas d’un màster universitari
Directory of Open Access Journals (Sweden)
Xavier Ma. Triadó i Ivern
2013-01-01
Full Text Available La implantació de les competències és una tasca que ha anat incorporant-se paulatinament pels docents de la universitat espanyola amb l’entrada en vigor del EEES. Tot i això, encara s’està lluny d’aconseguir nivells òptims d’avaluació de les mateixes. Aquest article permet reflexionar sobre algunes bones practiques al respecte i sobre les dificultats i limitacions que apareixen en voler implementar un canvi en les metodologies docents, en el marc d’un màster universitari. Els resultats indiquen el grau en què s’han avaluat i adquirit tant les competències genèriques com especifiques en l’educació superior.
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LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy
2013-01-01
Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984
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Directory of Open Access Journals (Sweden)
Sarah Fernandes Teixeira
2013-12-01
Full Text Available OBJECTIVE: To test the effectiveness of combining conventional antineoplastic drugs (cisplatin and etoposide with metformin in the treatment of non-small cell lung cancer in the NCI-H460 cell line, in order to develop new therapeutic options with high efficacy and low toxicity.METHODS: We used the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and calculated the combination index for the drugs studied.RESULTS: We found that the use of metformin as monotherapy reduced the metabolic viability of the cell line studied. Combining metformin with cisplatin or etoposide produced a synergistic effect and was more effective than was the use of cisplatin or etoposide as monotherapy.CONCLUSIONS: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. When metformin was combined with cisplatin or etoposide, the cell death rate was even higher.
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Enhanced Missing Proteins Detection in NCI60 Cell Lines Using an Integrative Search Engine Approach.
Guruceaga, Elizabeth; Garin-Muga, Alba; Prieto, Gorka; Bejarano, Bartolomé; Marcilla, Miguel; Marín-Vicente, Consuelo; Perez-Riverol, Yasset; Casal, J Ignacio; Vizcaíno, Juan Antonio; Corrales, Fernando J; Segura, Victor
2017-12-01
The Human Proteome Project (HPP) aims deciphering the complete map of the human proteome. In the past few years, significant efforts of the HPP teams have been dedicated to the experimental detection of the missing proteins, which lack reliable mass spectrometry evidence of their existence. In this endeavor, an in depth analysis of shotgun experiments might represent a valuable resource to select a biological matrix in design validation experiments. In this work, we used all the proteomic experiments from the NCI60 cell lines and applied an integrative approach based on the results obtained from Comet, Mascot, OMSSA, and X!Tandem. This workflow benefits from the complementarity of these search engines to increase the proteome coverage. Five missing proteins C-HPP guidelines compliant were identified, although further validation is needed. Moreover, 165 missing proteins were detected with only one unique peptide, and their functional analysis supported their participation in cellular pathways as was also proposed in other studies. Finally, we performed a combined analysis of the gene expression levels and the proteomic identifications from the common cell lines between the NCI60 and the CCLE project to suggest alternatives for further validation of missing protein observations.
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Heidari, Zahra; Feizi, Awat; Azadbakht, Leila; Sarrafzadegan, Nizal
2016-01-01
This study provides an assessment of usual intake distribution of vitamins and estimating prevalence of inadequacy and excess among a large representative sample of middle-aged and elderly people in central regions of Iran. A cross-sectional study that is a second follow-up to the Isfahan Cohort Study (ICS). The study setting included urban and rural areas from 3 cities (Isfahan, Najafabad, and Arak) in central regions of Iran. Subjects included 1922 people aged 40 years and older, with a mean age of 55.9 ± 10.6; 50.4% were male and the majority (79.3%) were urban. Dietary intakes were collected using a 24-hour recall and 2 food records. Distribution of vitamins intake was estimated using traditional and national cancer institute (NCI) methods. The proportion of subjects at risk of vitamin intake inadequacy or excess was estimated using the estimated average requirement (EAR) cut-point method and the tolerable upper intake levels (UL) index. There were differences between values obtained from traditional and NCI methods, particularly in the lower and upper percentiles of the intake distribution. High prevalence of inadequacies for vitamins A, D, E, B2, B3 (especially among females), and B9 was observed. Significant gender differences were found in terms of inadequate intakes for vitamins A, B1, B2, B3, B6, B9, B12, and C (p vitamin intake was observed in the middle-aged and elderly Iranian population. Nutritional interventions particularly through population-based educational programs in order to improve diet variety and consume nutrient supplements may be necessary.
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Persistent Identifier Practice for Big Data Management at NCI
Directory of Open Access Journals (Sweden)
Jingbo Wang
2017-04-01
Full Text Available The National Computational Infrastructure (NCI manages over 10 PB research data, which is co-located with the high performance computer (Raijin and an HPC class 3000 core OpenStack cloud system (Tenjin. In support of this integrated High Performance Computing/High Performance Data (HPC/HPD infrastructure, NCI’s data management practices includes building catalogues, DOI minting, data curation, data publishing, and data delivery through a variety of data services. The metadata catalogues, DOIs, THREDDS, and Vocabularies, all use different Uniform Resource Locator (URL styles. A Persistent IDentifier (PID service provides an important utility to manage URLs in a consistent, controlled and monitored manner to support the robustness of our national ‘Big Data’ infrastructure. In this paper we demonstrate NCI’s approach of utilising the NCI’s 'PID Service 'to consistently manage its persistent identifiers with various applications.
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Malalties de transmissió sexual a urgències pediàtriques
Díaz Sabogal, Diana; Curcoy Barcenilla, Ana Isabel; Trenchs Sainz de la Maza, Victoria; Giménez Roca, Clara; Luaces Cubells, Carles
2014-01-01
Determinar les característiques dels pacients diag- nosticats de malalties de transmissió sexual (MTS) a urgèn- cies i establir la freqüència en què són degudes a abús sexual. Mètode. Estudi retrospectiu fet entre el gener del 2007 i el desembre del 2011. S'inclouen els pacients menors de 18 anys diagnosticats a urgències d'MTS -infecció per Neisse- ria gonorrhoeae, Chlamydia trachomatis, Treponema palli- dum, , virus d'immunodeficiència humana (VIH), virus del pa- pil loma humà (VPH) i virus...
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There may be a new, more effective method for treating high-risk neuroblastoma, according to scientists at the Children’s Hospital of Philadelphia and collaborators in the Cancer and Inflammation Program at NCI at Frederick. Together, the groups published a study describing a previously unrecognized protein on neuroblastoma cells, called GPC2, as well as the creation of a
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NCI's Distributed Geospatial Data Server
Larraondo, P. R.; Evans, B. J. K.; Antony, J.
2016-12-01
Earth systems, environmental and geophysics datasets are an extremely valuable source of information about the state and evolution of the Earth. However, different disciplines and applications require this data to be post-processed in different ways before it can be used. For researchers experimenting with algorithms across large datasets or combining multiple data sets, the traditional approach to batch data processing and storing all the output for later analysis rapidly becomes unfeasible, and often requires additional work to publish for others to use. Recent developments on distributed computing using interactive access to significant cloud infrastructure opens the door for new ways of processing data on demand, hence alleviating the need for storage space for each individual copy of each product. The Australian National Computational Infrastructure (NCI) has developed a highly distributed geospatial data server which supports interactive processing of large geospatial data products, including satellite Earth Observation data and global model data, using flexible user-defined functions. This system dynamically and efficiently distributes the required computations among cloud nodes and thus provides a scalable analysis capability. In many cases this completely alleviates the need to preprocess and store the data as products. This system presents a standards-compliant interface, allowing ready accessibility for users of the data. Typical data wrangling problems such as handling different file formats and data types, or harmonising the coordinate projections or temporal and spatial resolutions, can now be handled automatically by this service. The geospatial data server exposes functionality for specifying how the data should be aggregated and transformed. The resulting products can be served using several standards such as the Open Geospatial Consortium's (OGC) Web Map Service (WMS) or Web Feature Service (WFS), Open Street Map tiles, or raw binary arrays under
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International Nuclear Information System (INIS)
He Wenqian; Liu Zhonghua
2007-01-01
Objective: To study the effect of bcl-2 antisense oligodexynucleotides on chemotherapy efficacy of Vp-16 on human small cell lung cancer cell line NCI-H69. Methods: Cultured NCI-H69 cells were derided into 4 groups: bcl-2 antisense oligodexynucleotides (ASODN) added, sense oligodexynucleotides (SODN) added, nonsense oligodexynucleotides (NSODN) added and control (no nucleotides added), the oligodexynucleotides were transfected into the cultured cells with oligofectamine. The cellular expression of Bcl-2 protein 72h later was examined with Western-Blot. The four different groups of cultured tumor cells were treated with etopside(Vp-16) at different concentrations (0, 0.25, 0.5, 1.0, 2.0 and 4.0 μg/ml) for 48hr then the cell survival fraction was assessed with MTY test. Results: The apoptotic rate of cells in the ASODN group was significantly higher than that of the control group, also, the survival fraction of cells in ASODN group was significantly lower than that of the control group. The Bcl-2 protein expression in ASODN group was significantly lower than that in the control group, but no inhibition was observed in SODN and NSODN groups. Conclusion: The bcl-2 ASODN could enhance the sensitivity to chemotherapy with Vp-16 in small cell lung cancer cell line NCI-H69 by effectively blocking bcl-2 gene expression. (authors)
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International Nuclear Information System (INIS)
Liao, Hui-Fen; Kuo Cheng-Deng; Yang, Yuh-Cheng; Lin, Chin-Ping; Tai, Hung-Chi; Chen, Yu-Jen; Chen, Yu-Yawn
2005-01-01
Resveratrol, a polyphenol in red wine, possesses many pharmacological activities including cardio-protection, chemoprevention, anti-tumor effects, and nuclear factor-kappa B (NF-κB) inactivation. The present study was designed to evaluate the effects and possible mechanism of resveratrol in enhancing radiosensitivity of lung cancer cells. Human non-small cell lung cancer NCI-H838 cells were irradiated with or without resveratrol pretreatment. The surviving fraction and sensitizer enhancement ratio (SER) were estimated by using a colony formation assay and linear-quadratic model. The cell-cycle distribution was evaluated by using prospidium iodide staining and flow cytometry. An enzyme-linked immunosorbent assay (ELISA)-based assay with immobilized oligonucleotide was performed to assess the DNA binding activity of NF-κB. Resveratrol had no direct growth-inhibitory effect on NCI-H838 cells treated for 24 hours with doses up to 25 μM. Pretreatment with resveratrol significantly enhanced cell killing by radiation, with an SER up to 2.2. Radiation activated NF-κB, an effect reversed by resveratrol pretreatment. Resveratrol resulted in a decrease of cells in the G 0 /G 1 phase and an increase in the S phase. Our results demonstrate that resveratrol enhances the radiosensitivity of NCI-H838 cells accompanied by NF-κB inhibition and S-phase arrest. (author)
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Crystallization of mouse S-adenosyl-l-homocysteine hydrolase
International Nuclear Information System (INIS)
Ishihara, Masaaki; Kusakabe, Yoshio; Ohsumichi, Tsuyoshi; Tanaka, Nobutada; Nakanishi, Masayuki; Kitade, Yukio; Nakamura, Kazuo T.
2010-01-01
Mouse S-adenosyl-l-homocysteine hydrolase has been crystallized in the presence of the reaction product adenosine. Diffraction data to 1.55 Å resolution were collected using synchrotron radiation. S-Adenosyl-l-homocysteine hydrolase (SAHH; EC 3.3.1.1) catalyzes the reversible hydrolysis of S-adenosyl-l-homocysteine to adenosine and l-homocysteine. For crystallographic investigations, mouse SAHH (MmSAHH) was overexpressed in bacterial cells and crystallized using the hanging-drop vapour-diffusion method in the presence of the reaction product adenosine. X-ray diffraction data to 1.55 Å resolution were collected from an orthorhombic crystal form belonging to space group I222 with unit-cell parameters a = 100.64, b = 104.44, c = 177.31 Å. Structural analysis by molecular replacement is in progress
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Three-Dimensional Reconstruction of the Mouse Nephron
DEFF Research Database (Denmark)
Zhai, Xiao-Yue; Thomsen, Jesper Skovhus; Birn, Henrik
2006-01-01
Renal function is crucially dependent on renal microstructure which provides the basis for the regulatory mechanisms that control the transport of water and solutes between filtrate and plasma and the urinary concentration. This study provides new, detailed information on mouse renal architecture...... and collecting ducts was performed on aligned digital images, obtained from 2.5-µm-thick serial sections of mouse kidneys. Important new findings were highlighted: (1) A tortuous course of the descending thin limbs of long-looped nephrons and a winding course of the thick ascending limbs of short-looped nephrons...
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Avaluació de competències professionalitzadores en els estudis de grau de comunicació audiovisual
Directory of Open Access Journals (Sweden)
Marina Romeo
2017-01-01
Full Text Available Els recents canvis en la formació universitària han comportat un destacable nivell de professionalització dels estudis i una constant adequació a les demandes socials. En aquest sentit, una de les necessitats per a la formació universitària a l'àrea de la comunicació audiovisual és desenvolupar en els estudiants competències professionalitzadores que els permetin trobar nínxols d'ocupació en un mercat altament competitiu i sotmès a canvis continus. Aquesta recerca té per objecte crear una rúbrica que permeti avaluar l'aprenentatge professionalitzador en els estudis de grau en comunicació audiovisual (CAV que es desenvolupen a Espanya. Per desenvolupar-la hem comptat amb ocupadors i acadèmics experts de l'àmbit de la comunicació audiovisual triats de forma intencional. La rúbrica final desenvolupada, a més de permetre avaluar el grau d'adquisició de les competències professionalitzadores en CAV, permet dibuixar un mapa clar de l'organització i adequació dels processos i metodologies docents. En aquest sentit, la rúbrica pot ser un instrument pedagògic clau per a una futura promoció d'estudiants, i es pot convertir en un instrument que afavoreixi l'avaluació formativa dels alumnes.
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The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), part of the National Institutes of Health, announces the release of an educational video titled “Proteogenomics Research: On the Frontier of Precision Medicine." Launched at the HUPO2017 Global Leadership Gala Dinner, catalyzed in part by the Cancer Moonshot initiative and featuring as keynote speaker the 47th Vice President of the United States of America Joseph R.
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Directory of Open Access Journals (Sweden)
Miguel Rodamilans-Pérez
2013-01-01
Full Text Available El Grup d'Innovació Docent Orfila, en el seu projecte per millorar la qualitat de la docència, està assajant la utilització del cinema amb finalitat didàctica. El material didàctic que hem desenvolupat en aquest projecte són petites seqüències de pel·lícules comercials de 3 a 5 minuts, per ser utilitzades com a elements il·lustratius del procés addictiu. Se seleccionen escenes de la filmografia i s'adeqüen als nostres programes docents. Es recull l'opinió dels professors participants, així com la dels alumnes, mitjançant una entrevista personal i una enquesta d'opinió, respectivament.De les entrevistes als professors i de les enquestes d'opinió dels alumnes, es dedueix un alt grau de satisfacció.
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Les experiències artístiques en l'espai públic. Art efímer com a catàlisi de la vida urbana
Directory of Open Access Journals (Sweden)
Lucila Urda Peña
2016-06-01
Full Text Available L'art efímer urbà, com a corrent d'expressió de pensament col·lectiu és una font de generació de projectes comunitaris en què els ciutadans poden recuperar "l'experiència de ciutat". La profusió de diverses manifestacions d'art efímer en ciutats de tot el món des de començaments del segle XXI està tenint conseqüències en l'espai urbà tant a nivell local com a nivell global. Una d'elles és la transformació del paisatge urbà, cada vegada més considerat com a escenari visible en projectes de regeneració urbana. A més de la transformació física també es produeixen canvis en les dinàmiques urbanes ja que els efectes de les intervencions tenen conseqüències més enllà dels canvis d'imatge. Els efectes socioeconòmics locals o fins i tot globals de les transformacions lligades a l'art efímer són cada vegada més evidents. Aquest article relata l'origen i desenvolupament de diverses manifestacions artístiques urbanes i reflexiona sobre les seves conseqüències en la vida urbana com a eina de transformació física i social.
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Clauser, Steven B; Johnson, Maureen R; O'Brien, Donna M; Beveridge, Joy M; Fennell, Mary L; Kaluzny, Arnold D
2009-09-26
In this article, we describe the National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) pilot and the evaluation designed to assess its role, function, and relevance to the NCI's research mission. In doing so, we describe the evolution of and rationale for the NCCCP concept, participating sites' characteristics, its multi-faceted aims to enhance clinical research and quality of care in community settings, and the role of strategic partnerships, both within and outside of the NCCCP network, in achieving program objectives. The evaluation of the NCCCP is conceptualized as a mixed method multi-layered assessment of organizational innovation and performance which includes mapping the evolution of site development as a means of understanding the inter- and intra-organizational change in the pilot, and the application of specific evaluation metrics for assessing the implementation, operations, and performance of the NCCCP pilot. The assessment of the cost of the pilot as an additional means of informing the longer-term feasibility and sustainability of the program is also discussed. The NCCCP is a major systems-level set of organizational innovations to enhance clinical research and care delivery in diverse communities across the United States. Assessment of the extent to which the program achieves its aims will depend on a full understanding of how individual, organizational, and environmental factors align (or fail to align) to achieve these improvements, and at what cost.
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Permanyer, Albert; Caja, Miguel Ángel
2005-01-01
La presencia de petróleo expulsado directamente de la roca madre de la Formación Armàncies, constituye un caso único para el estudio de los procesos de biodegradación aeróbica en petróleo. El estado de degradación bacteriana es moderado y está principalmente limitado a la alteración de n-alcanos, isoprenoides y algunos aromáticos. La cuantificación ha sido realizada mediante el contenido en sulfuro y con los marcadores moleculares de la fracción aromática. Los resultados obtenidos...
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This invention describes the discovery that specific p53 isoform increase the number of inducible pluripotent stem cells (iPS). It is known that the activity of p53 regulates the self-renewal and pluripotency of normal and cancer stem cells, and also affects re-programming efficiency of iPS cells. This p53 isoform-based technology provides a more natural process of increasing iPS cell production than previous methods of decreasing p53. NCI seeks licensees for this technology.
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ANIONIC POLYMERIZATION OF ALKYL METHACRYLATES INITIATED BY nBuCu(NCy2)Li
Institute of Scientific and Technical Information of China (English)
Bing-yong Han; Jian-guo Liang; Jian-min Lu; Feng An; Wan-tai Yang
2009-01-01
Anionic polymerization of methyl methacrylate (MMA), n-butyl methacrylate (nBMA) and glycidyl methacrylate (GMA) initiated by nBuCu(NCy2)Li (1) in tetrahydrofuran (THF) at -50℃ to -10℃ was investigated. It was found that the polymerization of MMA and nBMA initiated by 1 proceeded quantitatively in THF to afford PMMA and PBMA with polydispersity index 1.15-1.30 and nearly 100% initiator efficiencies at -10℃. The molecular weights increased linearly with the ratio of [monomer]/[1]. However, a post-polymerization experiment carried out on this system revealed a double polymer peak by GPC when fresh monomer was added after an interval of 10 rain. Polymerization of styrene could be initiated by 1, but the initiator efficiency was low.
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Kulakovskiy, Ivan V.; Vorontsov, Ilya E.; Yevshin, Ivan S.; Sharipov, Ruslan N.; Fedorova, Alla D.; Rumynskiy, Eugene I.; Medvedeva, Yulia A.; Magana-Mora, Arturo; Bajic, Vladimir B.; Papatsenko, Dmitry A.; Kolpakov, Fedor A.; Makeev, Vsevolod J.
2017-01-01
We present a major update of the HOCOMOCO collection that consists of patterns describing DNA binding specificities for human and mouse transcription factors. In this release, we profited from a nearly doubled volume of published in vivo experiments on transcription factor (TF) binding to expand the repertoire of binding models, replace low-quality models previously based on in vitro data only and cover more than a hundred TFs with previously unknown binding specificities. This was achieved by systematic motif discovery from more than five thousand ChIP-Seq experiments uniformly processed within the BioUML framework with several ChIP-Seq peak calling tools and aggregated in the GTRD database. HOCOMOCO v11 contains binding models for 453 mouse and 680 human transcription factors and includes 1302 mononucleotide and 576 dinucleotide position weight matrices, which describe primary binding preferences of each transcription factor and reliable alternative binding specificities. An interactive interface and bulk downloads are available on the web: http://hocomoco.autosome.ru and http://www.cbrc.kaust.edu.sa/hocomoco11. In this release, we complement HOCOMOCO by MoLoTool (Motif Location Toolbox, http://molotool.autosome.ru) that applies HOCOMOCO models for visualization of binding sites in short DNA sequences.
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Kulakovskiy, Ivan V.
2017-10-31
We present a major update of the HOCOMOCO collection that consists of patterns describing DNA binding specificities for human and mouse transcription factors. In this release, we profited from a nearly doubled volume of published in vivo experiments on transcription factor (TF) binding to expand the repertoire of binding models, replace low-quality models previously based on in vitro data only and cover more than a hundred TFs with previously unknown binding specificities. This was achieved by systematic motif discovery from more than five thousand ChIP-Seq experiments uniformly processed within the BioUML framework with several ChIP-Seq peak calling tools and aggregated in the GTRD database. HOCOMOCO v11 contains binding models for 453 mouse and 680 human transcription factors and includes 1302 mononucleotide and 576 dinucleotide position weight matrices, which describe primary binding preferences of each transcription factor and reliable alternative binding specificities. An interactive interface and bulk downloads are available on the web: http://hocomoco.autosome.ru and http://www.cbrc.kaust.edu.sa/hocomoco11. In this release, we complement HOCOMOCO by MoLoTool (Motif Location Toolbox, http://molotool.autosome.ru) that applies HOCOMOCO models for visualization of binding sites in short DNA sequences.
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Human · mouse genome analysis and radiation biology. Proceedings
International Nuclear Information System (INIS)
Hori, Tada-aki
1994-03-01
This issue is the collection of the papers presented at the 25th NIRS symposium on Human, Mouse Genome Analysis and Radiation Biology. The 14 of the presented papers are indexed individually. (J.P.N.)
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Readability of Online Patient Educational Resources Found on NCI-Designated Cancer Center Web Sites.
Rosenberg, Stephen A; Francis, David; Hullett, Craig R; Morris, Zachary S; Fisher, Michael M; Brower, Jeffrey V; Bradley, Kristin A; Anderson, Bethany M; Bassetti, Michael F; Kimple, Randall J
2016-06-01
The NIH and Department of Health & Human Services recommend online patient information (OPI) be written at a sixth grade level. We used a panel of readability analyses to assess OPI from NCI-Designated Cancer Center (NCIDCC) Web sites. Cancer.gov was used to identify 68 NCIDCC Web sites from which we collected both general OPI and OPI specific to breast, prostate, lung, and colon cancers. This text was analyzed by 10 commonly used readability tests: the New Dale-Chall Readability Formula, Flesch Reading Ease scale, Flesch-Kinaid Grade Level, FORCAST scale, Fry Readability Graph, Simple Measure of Gobbledygook test, Gunning Frequency of Gobbledygook index, New Fog Count, Raygor Readability Estimate Graph, and Coleman-Liau Index. We tested the hypothesis that the readability of NCIDCC OPI was written at the sixth grade level. Secondary analyses were performed to compare readability of OPI between comprehensive and noncomprehensive centers, by region, and to OPI produced by the American Cancer Society (ACS). A mean of 30,507 words from 40 comprehensive and 18 noncomprehensive NCIDCCs was analyzed (7 nonclinical and 3 without appropriate OPI were excluded). Using a composite grade level score, the mean readability score of 12.46 (ie, college level: 95% CI, 12.13-12.79) was significantly greater than the target grade level of 6 (middle-school: Preadability metrics (P<.05). ACS OPI provides easier language, at the seventh to ninth grade level, across all tests (P<.01). OPI from NCIDCC Web sites is more complex than recommended for the average patient. Copyright © 2016 by the National Comprehensive Cancer Network.
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Marshall, Emily L.; Borrego, David; Tran, Trung; Fudge, James C.; Bolch, Wesley E.
2018-03-01
Epidemiologic data demonstrate that pediatric patients face a higher relative risk of radiation induced cancers than their adult counterparts at equivalent exposures. Infants and children with congenital heart defects are a critical patient population exposed to ionizing radiation during life-saving procedures. These patients will likely incur numerous procedures throughout their lifespan, each time increasing their cumulative radiation absorbed dose. As continued improvements in long-term prognosis of congenital heart defect patients is achieved, a better understanding of organ radiation dose following treatment becomes increasingly vital. Dosimetry of these patients can be accomplished using Monte Carlo radiation transport simulations, coupled with modern anatomical patient models. The aim of this study was to evaluate the performance of the University of Florida/National Cancer Institute (UF/NCI) pediatric hybrid computational phantom library for organ dose assessment of patients that have undergone fluoroscopically guided cardiac catheterizations. In this study, two types of simulations were modeled. A dose assessment was performed on 29 patient-specific voxel phantoms (taken as representing the patient’s true anatomy), height/weight-matched hybrid library phantoms, and age-matched reference phantoms. Two exposure studies were conducted for each phantom type. First, a parametric study was constructed by the attending pediatric interventional cardiologist at the University of Florida to model the range of parameters seen clinically. Second, four clinical cardiac procedures were simulated based upon internal logfiles captured by a Toshiba Infinix-i Cardiac Bi-Plane fluoroscopic unit. Performance of the phantom library was quantified by computing both the percent difference in individual organ doses, as well as the organ dose root mean square values for overall phantom assessment between the matched phantoms (UF/NCI library or reference) and the patient
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Trasovares Navarrete, María Victoria
2004-01-01
Aquest treball, realitzat al Centre d'Atenció i Seguiment de Drogodependències (CASD) de Nou Barris, ha tingut com a objectiu principal observar el rol del psicòleg clínic en el procés d'avaluació i intervenció psicoterapèutica en pacients que presenten un trastorn per dependència de substàncies psicotròpiques. Este trabajo, realizado en el Centro de Atención y Seguimiento de Drogodependencias (CASD) de Nou Barris, ha tenido como principal objetivo observar el rol del psicólogo clínico en ...
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Directory of Open Access Journals (Sweden)
Laura Guitart Tarrés
2011-06-01
Full Text Available L’adaptació al nou espai europeu d’educació superior (EEES ha plantejat alguns canvis en l’enfocament de la formació universitària al nostre país. On abans era el docent el protagonista, ara és l’estudiant el que pren el rol d’actor principal de la seva formació, i l’aprenentatge s’orienta cap a una autonomia i reflexió més grans. En aquest escenari, les noves tecnologies ofereixen un ampli ventall d’opcions per millorar els processos formatius. En aquests sentit, el Grup d’Innovació Docent G•IDEA ha participat activament en aquest procés d’adaptació des de ja fa uns quants anys, i ha creat una sèrie de recursos docents digitals que han estat àmpliament provats en diversos ensenyaments de la Facultat d’Economia i Empresa de la Universitat de Barcelona. L’objectiu d’aquest article és presentar el protocol dissenyat per l’equip d’investigadors del G•IDEA per implantar aquestes eines didàctiques (webquestes i exercicis tutoritzats, i també els resultats d’una enquesta de satisfacció sobre les competències i habilitats adquirides pels nostres estudiants en la utilització dels recursos. Els resultats mostren, d’una banda, que no ha estat possible crear un mateix protocol aplicable a tots els recursos, a causa de les diferències en els objectius didàctics de les distintes eines docents implantades. D’altra banda, la valoració que els estudiants fan de la utilització de les eines és molt positiva, tot i que hi ha algunes diferències entre els recursos analitzats. Conèixer la valoració que l’alumnat fa d’aquests recursos permet al grup d’investigadors poder-los millorar i adequar al perfil dels estudiants perquè aquests en puguin treure el màxim profit possible.
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Directory of Open Access Journals (Sweden)
Fennell Mary L
2009-09-01
Full Text Available Abstract Background In this article, we describe the National Cancer Institute (NCI Community Cancer Centers Program (NCCCP pilot and the evaluation designed to assess its role, function, and relevance to the NCI's research mission. In doing so, we describe the evolution of and rationale for the NCCCP concept, participating sites' characteristics, its multi-faceted aims to enhance clinical research and quality of care in community settings, and the role of strategic partnerships, both within and outside of the NCCCP network, in achieving program objectives. Discussion The evaluation of the NCCCP is conceptualized as a mixed method multi-layered assessment of organizational innovation and performance which includes mapping the evolution of site development as a means of understanding the inter- and intra-organizational change in the pilot, and the application of specific evaluation metrics for assessing the implementation, operations, and performance of the NCCCP pilot. The assessment of the cost of the pilot as an additional means of informing the longer-term feasibility and sustainability of the program is also discussed. Summary The NCCCP is a major systems-level set of organizational innovations to enhance clinical research and care delivery in diverse communities across the United States. Assessment of the extent to which the program achieves its aims will depend on a full understanding of how individual, organizational, and environmental factors align (or fail to align to achieve these improvements, and at what cost.
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Chen, Jun; Han, Han; Wang, Bin; Shi, Liying
2016-07-01
The Sendai virus strain Tianjin is a novel genotype of the Sendai virus. In previous studies, ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) demonstrated antitumor effects on human breast cancer cells. The aim of the present study was to investigate the in vitro antitumor effects of UV-Tianjin on the human cervical carcinoma HeLa, human small cell lung cancer NCI-H446 and human hepatocellular carcinoma Hep 3B cell lines, and the possible underlying mechanisms of these antitumor effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that UV-Tianjin treatment inhibited the proliferation of HeLa, NCI-H446 and Hep 3B cells in a dose- and time-dependent manner. Hoechst and Annexin V-fluorescein isothiocyanate/propidium iodide double staining indicated that UV-Tianjin induced dose-dependent apoptosis in all three cell lines with the most significant effect observed in the HeLa cell line. In the HeLa cell line, UV-Tianjin-induced apoptosis was further confirmed by the disruption of the mitochondria membrane potential and the activation of caspases, as demonstrated by fluorescent cationic dye and colorimetric assays, respectively. In addition, western blot analysis revealed that UV-Tianjin treatment resulted in significant upregulation of cytochrome c , apoptosis protease activating factor-1, Fas, Fas ligand and Fas-associated protein with death domain, and activated caspase-9, -8 and -3 in HeLa cells. Based on these results, it is hypothesized that UV-Tianjin exhibits anticancer activity in HeLa, NCI-H446 and Hep 3B cell lines via the induction of apoptosis. In conclusion, the results of the present study indicate that in the HeLa cell line, intrinsic and extrinsic apoptotic pathways may be involved in UV-Tianjin-induced apoptosis.
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Patient-Derived Antibody Targets Tumor Cells
An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.
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Directory of Open Access Journals (Sweden)
Eastman Alan
2011-05-01
Full Text Available Abstract Background The Mre11/Rad50/Nbs1 (MRN complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged. Such defects may elicit sensitivity to selected drugs providing a chemical synthetic lethal interaction that could be used to target therapy to tumors with these defects. The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity. Methods We screened the NCI60 panel in search of cell lines that express low levels of MRN proteins, or that fail to arrest in S-phase in response to the topisomerase I inhibitor SN38. The NCI COMPARE program was used to discover compounds that preferentially target cells with these phenotypes. Results HCT116 cells were initially identified as defective in MRN and S phase arrest. Transfection with Mre11 also elevated Rad50 and Nbs1, and rescued the defective S-phase arrest. Cells of the NCI60 panel exhibited a large range of protein expression but a strong correlation existed between Mre11, Rad50 and Nbs1 consistent with complex formation determining protein stability. Mre11 mRNA correlated best with protein level suggesting it was the primary determinant of the overall level of the complex. Three other cell lines failed to arrest in response to SN38, two of which also had low MRN. However, other cell lines with low MRN still arrested suggesting low MRN does not predict an inability to arrest. Many compounds, including a family of benzothiazoles, correlated with the failure to arrest in S phase. The activity of benzothiazoles has been attributed to metabolic activation and DNA alkylation, but we note several cell lines in which sensitivity does not correlate with metabolism. We propose that the checkpoint defect imposes an additional mechanism of sensitivity on cells. Conclusions We have identified cells with possible defects in the MRN complex
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International Nuclear Information System (INIS)
Garner, Kristen M; Eastman, Alan
2011-01-01
The Mre11/Rad50/Nbs1 (MRN) complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged. Such defects may elicit sensitivity to selected drugs providing a chemical synthetic lethal interaction that could be used to target therapy to tumors with these defects. The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity. We screened the NCI60 panel in search of cell lines that express low levels of MRN proteins, or that fail to arrest in S-phase in response to the topisomerase I inhibitor SN38. The NCI COMPARE program was used to discover compounds that preferentially target cells with these phenotypes. HCT116 cells were initially identified as defective in MRN and S phase arrest. Transfection with Mre11 also elevated Rad50 and Nbs1, and rescued the defective S-phase arrest. Cells of the NCI60 panel exhibited a large range of protein expression but a strong correlation existed between Mre11, Rad50 and Nbs1 consistent with complex formation determining protein stability. Mre11 mRNA correlated best with protein level suggesting it was the primary determinant of the overall level of the complex. Three other cell lines failed to arrest in response to SN38, two of which also had low MRN. However, other cell lines with low MRN still arrested suggesting low MRN does not predict an inability to arrest. Many compounds, including a family of benzothiazoles, correlated with the failure to arrest in S phase. The activity of benzothiazoles has been attributed to metabolic activation and DNA alkylation, but we note several cell lines in which sensitivity does not correlate with metabolism. We propose that the checkpoint defect imposes an additional mechanism of sensitivity on cells. We have identified cells with possible defects in the MRN complex and S phase arrest, and a series of compounds that may
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Narayan, Malathi; Seeley, Kent W; Jinwal, Umesh K
2016-06-01
Mass spectrometry data collected in a study analyzing the effect of withaferin A (WA) on a mouse microglial (N9) cell line is presented in this article. Data was collected from SILAC-based quantitative analysis of lysates from mouse microglial cells treated with either WA or DMSO vehicle control. This article reports all the proteins that were identified in this analysis. The data presented here is related to the published research article on the effect of WA on the differential regulation of proteins in mouse microglial cells [1]. Mass spectrometry data has also been deposited in the ProteomeXchange with the identifier PXD003032.
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Centralized mouse repositories.
Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T
2012-10-01
Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.
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Kläring, K.; Hanske, L.; Bui, T.P.N.; Charrier, C.; Blaut, M.; Haller, D.; Plugge, C.M.; Clavel, T.
2013-01-01
Whilst creating a bacterial collection of strains from the mouse intestine, we isolated a Gram-negative, spore-forming, non-motile and strictly anaerobic rod-shaped bacterium from the caecal content of a TNFdeltaARE mouse. The isolate, referred to as strain SRB-521-5-IT, was originally cultured on a
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Developmental immunolocalization of the Klotho protein in mouse kidney epithelial cells
Directory of Open Access Journals (Sweden)
J.H. Song
2014-01-01
Full Text Available A defect in Klotho gene expression in the mouse results in a syndrome that resembles rapid human aging. In this study, we investigated the detailed distribution and the time of the first appearance of Klotho in developing and adult mouse kidney. Kidneys from 16-(F16, 18-(F18 and 20-day-old (F20 fetuses, 1- (P1, 4- (P4, 7- (P7, 14- (P14, and 21-day-old (P21 pups and adults were processed for immunohistochemistry and immunoblot analyses. In the developing mouse kidney, Klotho immunoreactivity was initially observed in a few cells of the connecting tubules (CNT of 18-day-old fetus (F and in the medullary collecting duct (MCD and distal nephron of the F16 developing kidney. In F20, Klotho immunoreactivity was increased in CNT and additionally observed in the outer portion of MCD and tip of the renal papilla. During the first 3 weeks after birth, Klotho-positive cells gradually disappeared from the MCD due to apoptosis, but remained in the CNT and cortical collecting ducts (CCD. In the adult mouse, the Klotho protein was expressed only in a few cells of the CNT and CCD in cortical area. Also, Klotho immunoreactivity was observed in the aquaporin 2-positive CNT, CCD, and NaCl co-transporter-positive distal convoluted tubule (DCT cells and type B and nonA-nonB intercalated cells of CNT, DCT, and CCD. Collectively, our data indicate that immunolocalization of Klotho is closely correlated with proliferation in the intercalated cells of CNT and CCD from aging, and may be involved in the regulation of tubular proliferation.
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Nuclear hormone receptor expression in mouse kidney and renal cell lines.
Directory of Open Access Journals (Sweden)
Daisuke Ogawa
Full Text Available Nuclear hormone receptors (NHRs are transcription factors that regulate carbohydrate and lipid metabolism, immune responses, and inflammation. Although several NHRs, including peroxisome proliferator-activated receptor-γ (PPARγ and PPARα, demonstrate a renoprotective effect in the context of diabetic nephropathy (DN, the expression and role of other NHRs in the kidney are still unrecognized. To investigate potential roles of NHRs in the biology of the kidney, we used quantitative real-time polymerase chain reaction to profile the expression of all 49 members of the mouse NHR superfamily in mouse kidney tissue (C57BL/6 and db/m, and cell lines of mesangial (MES13, podocyte (MPC, proximal tubular epithelial (mProx24 and collecting duct (mIMCD3 origins in both normal and high-glucose conditions. In C57BL/6 mouse kidney cells, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter transcription factor II (COUP-TFII and COUP-TFIII were highly expressed. During hyperglycemia, the expression of the NHR 4A subgroup including neuron-derived clone 77 (Nur77, nuclear receptor-related factor 1, and neuron-derived orphan receptor 1 significantly increased in diabetic C57BL/6 and db/db mice. In renal cell lines, PPARδ was highly expressed in mesangial and proximal tubular epithelial cells, while COUP-TFs were highly expressed in podocytes, proximal tubular epithelial cells, and collecting duct cells. High-glucose conditions increased the expression of Nur77 in mesangial and collecting duct cells, and liver x receptor α in podocytes. These data demonstrate NHR expression in mouse kidney cells and cultured renal cell lines and suggest potential therapeutic targets in the kidney for the treatment of DN.
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Directory of Open Access Journals (Sweden)
Malathi Narayan
2016-06-01
Full Text Available Mass spectrometry data collected in a study analyzing the effect of withaferin A (WA on a mouse microglial (N9 cell line is presented in this article. Data was collected from SILAC-based quantitative analysis of lysates from mouse microglial cells treated with either WA or DMSO vehicle control. This article reports all the proteins that were identified in this analysis. The data presented here is related to the published research article on the effect of WA on the differential regulation of proteins in mouse microglial cells [1]. Mass spectrometry data has also been deposited in the ProteomeXchange with the identifier http://www.ebi.ac.uk/pride/archive/projects/PXD003032.
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Testing lung cancer drugs and therapies in mice
National Cancer Institute (NCI) investigators have designed a genetically engineered mouse for use in the study of human lung squamous cell carcinoma (SCC). SCC is a type of non-small cell lung carcinoma, one of the most common types of lung cancer, with
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DEFF Research Database (Denmark)
Nissen, K.K.; Vogel, Ulla Birgitte; Nexo, B.A.
2009-01-01
the correlations between the responses of the NCI60 cells to different anticancer drugs and their respective alleles of five DNA polymorphisms located in a cancer-related chromosomal area. One polymorphism, located in the 5' noncoding region of the gene ASE-1, alias CD3EAP, proved to be associated with drug...
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Koscielny, Gautier; Yaikhom, Gagarine; Iyer, Vivek; Meehan, Terrence F.; Morgan, Hugh; Atienza-Herrero, Julian; Blake, Andrew; Chen, Chao-Kung; Easty, Richard; Di Fenza, Armida; Fiegel, Tanja; Grifiths, Mark; Horne, Alan; Karp, Natasha A.; Kurbatova, Natalja; Mason, Jeremy C.; Matthews, Peter; Oakley, Darren J.; Qazi, Asfand; Regnart, Jack; Retha, Ahmad; Santos, Luis A.; Sneddon, Duncan J.; Warren, Jonathan; Westerberg, Henrik; Wilson, Robert J.; Melvin, David G.; Smedley, Damian; Brown, Steve D. M.; Flicek, Paul; Skarnes, William C.; Mallon, Ann-Marie; Parkinson, Helen
2014-01-01
The International Mouse Phenotyping Consortium (IMPC) web portal (http://www.mousephenotype.org) provides the biomedical community with a unified point of access to mutant mice and rich collection of related emerging and existing mouse phenotype data. IMPC mouse clinics worldwide follow rigorous highly structured and standardized protocols for the experimentation, collection and dissemination of data. Dedicated ‘data wranglers’ work with each phenotyping center to collate data and perform quality control of data. An automated statistical analysis pipeline has been developed to identify knockout strains with a significant change in the phenotype parameters. Annotation with biomedical ontologies allows biologists and clinicians to easily find mouse strains with phenotypic traits relevant to their research. Data integration with other resources will provide insights into mammalian gene function and human disease. As phenotype data become available for every gene in the mouse, the IMPC web portal will become an invaluable tool for researchers studying the genetic contributions of genes to human diseases. PMID:24194600
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2011-04-22
... questions with inquiries into the communication channels through which understanding is being obtained, and... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; Comment... content of the survey will focus on understanding the degree to which members of the general population...
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Matsui, Elizabeth C.; Krop, Esmeralda J. M.; Diette, Gregory B.; Aalberse, Rob C.; Smith, Abigail L.; Eggleston, Peyton A.
2004-01-01
Although there is evidence that contact with mice is associated with IgE-mediated mouse sensitization and mouse specific antibody responses, the exposure-response relationships remain unclear. To determine whether IgE-mediated mouse sensitization and mouse specific IgG (mIgG) and mIgG4 levels
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Energy Technology Data Exchange (ETDEWEB)
Udhay Ravishankar; Milos manic
2013-08-01
This paper presents a micro-grid simulator tool useful for implementing and testing multi-agent controllers (SGridSim). As a common engineering practice it is important to have a tool that simplifies the modeling of the salient features of a desired system. In electric micro-grids, these salient features are the voltage and power distributions within the micro-grid. Current simplified electric power grid simulator tools such as PowerWorld, PowerSim, Gridlab, etc, model only the power distribution features of a desired micro-grid. Other power grid simulators such as Simulink, Modelica, etc, use detailed modeling to accommodate the voltage distribution features. This paper presents a SGridSim micro-grid simulator tool that simplifies the modeling of both the voltage and power distribution features in a desired micro-grid. The SGridSim tool accomplishes this simplified modeling by using Effective Node-to-Node Complex Impedance (EN2NCI) models of components that typically make-up a micro-grid. The term EN2NCI models means that the impedance based components of a micro-grid are modeled as single impedances tied between their respective voltage nodes on the micro-grid. Hence the benefit of the presented SGridSim tool are 1) simulation of a micro-grid is performed strictly in the complex-domain; 2) faster simulation of a micro-grid by avoiding the simulation of detailed transients. An example micro-grid model was built using the SGridSim tool and tested to simulate both the voltage and power distribution features with a total absolute relative error of less than 6%.
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Erwin, Cathleen O; Dias, Ashley M
2016-01-01
The study employs a dialogic public relations framework to explore the utilization of the Internet for fundraising by nonprofit health care organizations-specifically, NCI-designated cancer centers. Cancer centers have been noted for effective websites and for being highly engaged in fundraising, which is characterized as relationship marketing. Results indicate all but one cancer center use websites and social media for fundraising but are limited in capacity for two-way symmetrical dialogue. Results are discussed and recommendations are made for future research.
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Detecting Role Errors in the Gene Hierarchy of the NCI Thesaurus
Directory of Open Access Journals (Sweden)
Yehoshua Perl
2008-01-01
Full Text Available Gene terminologies are playing an increasingly important role in the ever-growing field of genomic research. While errors in large, complex terminologies are inevitable, gene terminologies are even more susceptible to them due to the rapid growth of genomic knowledge and the nature of its discovery. It is therefore very important to establish quality- assurance protocols for such genomic-knowledge repositories. Different kinds of terminologies oftentimes require auditing methodologies adapted to their particular structures. In light of this, an auditing methodology tailored to the characteristics of the NCI Thesaurus’s (NCIT’s Gene hierarchy is presented. The Gene hierarchy is of particular interest to the NCIT’s designers due to the primary role of genomics in current cancer research. This multiphase methodology focuses on detecting role-errors, such as missing roles or roles with incorrect or incomplete target structures, occurring within that hierarchy. The methodology is based on two kinds of abstraction networks, called taxonomies, that highlight the role distribution among concepts within the IS-A (subsumption hierarchy. These abstract views tend to highlight portions of the hierarchy having a higher concentration of errors. The errors found during an application of the methodology
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Eto, Tomoo; Takahashi, Riichi; Kamisako, Tsutomu
2015-04-01
Strain preservation of experimental animals is crucial for experimental reproducibility. Maintaining complete animal strains, however, is costly and there is a risk for genetic mutations as well as complete loss due to disasters or illness. Therefore, the development of effective vitrification techniques for cryopreservation of multiple experimental animal strains is important. We examined whether a vitrification method using cryoprotectant solutions, P10 and PEPeS, is suitable for preservation of multiple inbred and outbred mouse strains. First, we investigated whether our vitrification method using cryoprotectant solutions was suitable for two-cell stage mouse embryos. In vitro development of embryos exposed to the cryoprotectant solutions was similar to that of fresh controls. Further, the survival rate of the vitrified embryos was extremely high (98.1%). Next, we collected and vitrified two-cell stage embryos of 14 mouse strains. The average number of embryos obtained from one female was 7.3-33.3. The survival rate of vitrified embryos ranged from 92.8% to 99.1%, with no significant differences among mouse strains. In vivo development did not differ significantly between fresh controls and vitrified embryos of each strain. For strain preservation using cryopreserved embryos, two offspring for inbred lines and one offspring for outbred lines must be produced from two-cell stage embryos collected from one female. The expected number of surviving fetuses obtained from embryos collected from one female of either the inbred or outbred strains ranged from 2.9 to 19.5. The findings of the present study indicated that this vitrification method is suitable for strain preservation of multiple mouse strains. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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Incidència i consequències de les caigudes en les persones grans que viuen a la comunitat
Salvà, Antoni
2016-01-01
ANTECEDENTS I OBJECTIUS: Avaluar la incidència de les caigudes en funció dels factors sociodemogràfics i de salut, i determinar llurs conseqüències físiques, psicològiques i socials. Desenvolupar una nova eina d'avaluació del factor de risc amb l'objectiu d'assolir una intervenció preventiva multifactorial. METODOLOGIA: Estudi poblacional prospectiu, que inclou una cohort representativa de 448 persones grans, de 65 anys o més, que viuen a la ciutat de Mataró (Espanya). Hem fet una avaluació b...
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DEFF Research Database (Denmark)
Liu, L; Vachon, P H; Kuang, W
1997-01-01
. To analyze the biological roles of adhalin, we cloned the mouse adhalin cDNA, raised peptide-specific antibodies to its cytoplasmic domain, and examined its expression and localization in vivo and in vitro. The mouse adhalin sequence was 80% identical to that of human, rabbit, and hamster. Adhalin...... was specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types. Adhalin expression in embryonic mouse muscle was coincident with primary myogenesis. Its expression was found to be up-regulated at mRNA and protein levels during myogenic differentiation...
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Electroporation of Postimplantation Mouse Embryos In Utero.
Huang, Cheng-Chiu; Carcagno, Abel
2018-02-01
Gene transfer by electroporation is possible in mouse fetuses within the uterus. As described in this protocol, the pregnant female is anesthetized, the abdominal cavity is opened, and the uterus with the fetuses is exteriorized. A solution of plasmid DNA is injected through the uterine wall directly into the fetus, typically into a cavity like the brain ventricle, guided by fiber optic illumination. Electrodes are positioned on the uterus around the region of the fetus that was injected, and electrical pulses are delivered. The uterus is returned to the abdominal cavity, the body wall is sutured closed, and the female is allowed to recover. The manipulated fetuses can then be collected and analyzed at various times after the electroporation. This method allows experimental access to later-stage developing mouse embryos. © 2018 Cold Spring Harbor Laboratory Press.
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DEFF Research Database (Denmark)
Kuhre, Rune Ehrenreich; Albrechtsen, Nicolai Jacob Wewer; Windeløv, Johanne Agerlin
2014-01-01
and whether this varied with the six different locations. We also analyzed the amidation in 3 GLP-1 secreting cell lines (GLUTag, NCI-H716 and STC-1). To our surprise there were marked differences between the 3 species with respect to the concentration of GLP-1 in gut. In the mouse, concentrations increased...... sites, whereas rats and pigs on average had around 2.5 and 4 times higher levels of amidated compared to non-amidated GLP-1, although the ratio varied depending upon the location. GLUTag, NCI-H716 and STC-1 cells all exhibited partial amidation with 2-4 times higher levels of amidated compared to non...
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Molecular cloning, expression, and characterization of mouse amine N-sulfotransferases
International Nuclear Information System (INIS)
Takahashi, Saki; Sakakibara, Yoichi; Mishiro, Emi; Kouriki, Haruna; Nobe, Rika; Kurogi, Katsuhisa; Yasuda, Shin; Liu, M.-C.; Suiko, Masahito
2008-01-01
By searching the GenBank database, we recently identified a novel mouse cytosolic sulfotransferase (SULT) cDNA (IMAGE Clone ID 679629) and a novel mouse SULT gene (LOC 215895). Sequence analysis revealed that both mouse SULTs belong to the cytosolic SULT3 gene family. The recombinant form of these two newly identified SULTs, designated SULT3A1 and SULT3A2, were expressed using the pGEX-4T-1 glutathione S-transferase fusion system and purified from transformed BL21 Escherichia coli cells. Both purified SULT3A1 and SULT3A2 exhibited strong amine N-sulfonating activities toward 1-naphthylamine among a variety of endogenous and xenobiotic compounds tested as substrates. Kinetic constants of the sulfation of 1-naphthylamine and 1-naphthol by these two enzymes were determined. Collectively, these results imply that these two amine-sulfonating SULT3s may play essential roles in the metabolism and detoxification of aromatic amine compounds in the body
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Enhancement of NMRI Mouse Embryo Development In vitro
Directory of Open Access Journals (Sweden)
Abedini, F.
2013-12-01
Full Text Available Most of the systematic studies used in the development of human embryo culture media have been done first on mouse embryos. The general use of NMRI outbred mice is a model for toxicology, teratology and pharmacology. NMRI mouse embryo exhibit the two-cell block in vitro. The objective of this study was to evaluate and compare the effects of four kinds of culture media on the development of zygotes (NMRI after embryo vitrification. One-cell mouse embryos were obtained from NMRI mice after superovulation and mating with adult male NMRI mice. And then randomly divided into 4 groups for culture in four different cultures media including: M16 (A, DMEM/Ham, F-12 (B, DMEM/Ham's F-12 co-culture with Vero cells(C and DMEM/Ham's F-12 co-culture with MEF cells (D. Afterward all of the embryos were vitrified in EFS40 solution and collected. Results of our study revealed, more blastocysts significantly were developed with co-culture with MEF cells in DMEM/Ham's F-12 medium. More research needed to understand the effect of other components of culture medium, and co-culture on NMRI embryo development.
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NCI Think Tank Concerning the Identifiability of Biospecimens and “-Omic” Data
Weil, Carol J.; Mechanic, Leah E.; Green, Tiffany; Kinsinger, Christopher; Lockhart, Nicole C.; Nelson, Stefanie A.; Rodriguez, Laura L.; Buccini, Laura D.
2014-01-01
On June 11 and 12, 2012, the National Cancer Institute (NCI) hosted a think tank concerning the identifiability of biospecimens and “omic” Data in order to explore challenges surrounding this complex and multifaceted topic. The think tank brought together forty-six leaders from several fields, including cancer genomics, bioinformatics, human subject protection, patient advocacy, and commercial genetics. The first day involved presentations regarding the state of the science of re-identification; current and proposed regulatory frameworks for assessing identifiability; developments in law, industry and biotechnology; and the expectations of patients and research participants. The second day was spent by think tank participants in small break-out groups designed to address specific sub-topics under the umbrella issue of identifiability, including considerations for the development of best practices for data sharing and consent, and targeted opportunities for further empirical research. We describe the outcomes of this two day meeting, including two complimentary themes that emerged from moderated discussions following the presentations on Day 1, and ideas presented for further empirical research to discern the preferences and concerns of research participants about data sharing and individual identifiability. PMID:23579437
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Experiències de realitat augmentada en biblioteques : estat de la qüestió
Directory of Open Access Journals (Sweden)
Arroyo Vázquez, Natalia
2016-06-01
Full Text Available Objectiu: donar a conèixer les experiències més significatives d'ús de la realitat augmentada en biblioteques, amb una especial atenció als resultats obtinguts, les aportacions i les limitacions que s'han de tenir en compte. -- Metodologia: revisió bibliogràfica, selecció i anàlisi d'experiències sobre l'ús de realitat augmentada en biblioteques. -- Resultats: tot i ser una tecnologia recent, són diversos els exemples d'ús de la realitat augmentada en biblioteques. No obstant això, es fa necessari donar a conèixer els resultats d'aquestes experiències, de manera que puguin servir no solament com a model, sinó també per conèixer què és el que funciona. Es presenta als professionals un catàleg d'usos de la realitat augmentada en biblioteques, dels quals s'analitzen de forma crítica els possibles beneficis i limitacions, i s'agrupen en set apartats segons la utilitat: geolocalització, contextualització històrica, exposicions i altres activitats, publicacions, enriquiment dels espais físics, alfabetització i ludificació i, finalment, usos professionals.Objetivo: dar a conocer las experiencias más significativas de uso de la realidad aumentada en bibliotecas, con una especial atención a los resultados obtenidos, las aportaciones y las limitaciones que se deben tener en cuenta. -- Metodología: revisión bibliográfica, selección y análisis de experiencias sobre el uso de realidad aumentada en bibliotecas. -- Resultados: a pesar de ser una tecnología reciente, son varios los ejemplos de uso de la realidad aumentada en bibliotecas. Sin embargo, se hace necesario dar a conocer los resultados de dichas experiencias, de forma que puedan servir no solo como modelo, sino también para conocer qué es lo que funciona. Se presenta a los profesionales un catálogo de usos de la realidad aumentada en bibliotecas, analizados de forma crítica sus posibles beneficios y limitaciones, agrupados en siete apartados según la utilidad
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Experiències de realitat augmentada en biblioteques : estat de la qüestió
Directory of Open Access Journals (Sweden)
Arroyo Vázquez, Natalia
2016-06-01
Full Text Available Objectiu: donar a conèixer les experiències més significatives d'ús de la realitat augmentada en biblioteques, fent una especial atenció als resultats obtinguts, les aportacions i les limitacions que s'han de tenir en compte. -- Metodologia: revisió bibliogràfica, selecció i anàlisi d'experiències sobre l'ús de la realitat augmentada en biblioteques. -- Resultats: malgrat ser una tecnologia recent, els exemples d'ús de la realitat augmentada en biblioteques són diversos. No obstant això, es fa necessari donar a conèixer els resultats d'aquestes experiències, de manera que puguin servir no solament com a model, sinó també per conèixer què és el que funciona. Es presenta als professionals un catàleg d'usos de la realitat augmentada en biblioteques, dels quals s'analitzen de forma crítica els possibles beneficis i limitacions, i s'agrupen en set apartats segons la utilitat: geolocalització, contextualització històrica, exposicions i altres activitats, publicacions, enriquiment dels espais físics, alfabetització i ludificació i, finalment, usos professionals.Objetivo: dar a conocer las experiencias más significativas de uso de la realidad aumentada en bibliotecas, con una especial atención a los resultados obtenidos, las aportaciones y las limitaciones que se deben tener en cuenta. -- Metodología: revisión bibliográfica, selección y análisis de experiencias sobre el uso de la realidad aumentada en bibliotecas. -- Resultados: a pesar de ser una tecnología reciente, son varios los ejemplos de uso de la realidad aumentada en bibliotecas. Sin embargo, se hace necesario dar a conocer los resultados de dichas experiencias, de forma que puedan servir no solo como modelo, sino también para conocer qué es lo que funciona. Se presenta a los profesionales un catálogo de usos de la realidad aumentada en bibliotecas, analizados de forma crítica sus posibles beneficios y limitaciones, agrupados en siete apartados según la
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An ensemble based top performing approach for NCI-DREAM drug sensitivity prediction challenge.
Directory of Open Access Journals (Sweden)
Qian Wan
Full Text Available We consider the problem of predicting sensitivity of cancer cell lines to new drugs based on supervised learning on genomic profiles. The genetic and epigenetic characterization of a cell line provides observations on various aspects of regulation including DNA copy number variations, gene expression, DNA methylation and protein abundance. To extract relevant information from the various data types, we applied a random forest based approach to generate sensitivity predictions from each type of data and combined the predictions in a linear regression model to generate the final drug sensitivity prediction. Our approach when applied to the NCI-DREAM drug sensitivity prediction challenge was a top performer among 47 teams and produced high accuracy predictions. Our results show that the incorporation of multiple genomic characterizations lowered the mean and variance of the estimated bootstrap prediction error. We also applied our approach to the Cancer Cell Line Encyclopedia database for sensitivity prediction and the ability to extract the top targets of an anti-cancer drug. The results illustrate the effectiveness of our approach in predicting drug sensitivity from heterogeneous genomic datasets.
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Developing Cancer Informatics Applications and Tools Using the NCI Genomic Data Commons API.
Wilson, Shane; Fitzsimons, Michael; Ferguson, Martin; Heath, Allison; Jensen, Mark; Miller, Josh; Murphy, Mark W; Porter, James; Sahni, Himanso; Staudt, Louis; Tang, Yajing; Wang, Zhining; Yu, Christine; Zhang, Junjun; Ferretti, Vincent; Grossman, Robert L
2017-11-01
The NCI Genomic Data Commons (GDC) was launched in 2016 and makes available over 4 petabytes (PB) of cancer genomic and associated clinical data to the research community. This dataset continues to grow and currently includes over 14,500 patients. The GDC is an example of a biomedical data commons, which collocates biomedical data with storage and computing infrastructure and commonly used web services, software applications, and tools to create a secure, interoperable, and extensible resource for researchers. The GDC is (i) a data repository for downloading data that have been submitted to it, and also a system that (ii) applies a common set of bioinformatics pipelines to submitted data; (iii) reanalyzes existing data when new pipelines are developed; and (iv) allows users to build their own applications and systems that interoperate with the GDC using the GDC Application Programming Interface (API). We describe the GDC API and how it has been used both by the GDC itself and by third parties. Cancer Res; 77(21); e15-18. ©2017 AACR . ©2017 American Association for Cancer Research.
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2013-07-23
... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Submission for OMB Review; 30-day Comment Request: Financial Sustainability of Human Tissue Biobanking (NCI) SUMMARY: Under the... Collection: Financial Sustainability of Human Tissue Biobanking, 0925-NEW, National Cancer Institute (NCI...
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The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.
Eppig, Janan T; Blake, Judith A; Bult, Carol J; Kadin, James A; Richardson, Joel E
2015-01-01
The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
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Directory of Open Access Journals (Sweden)
Merce TEIXIDO
2014-03-01
Full Text Available This paper presents the optimization of a virtual mouse called HeadMouse in order to foster its classroom use by children with physical disabilities. HeadMouse is an absolute virtual mouse that converts head movements in cursor displacement and facial gestures in click actions. The virtual mouse combines different image processing algorithms: face detection, pattern matching and optical flow in order to emulate the behaviour of a conventional computer mouse. The original implementation of HeadMouse requires large computational power and this paper proposes specific optimizations in order to enable its use by children with disabilities in standard low cost classroom computers.
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The completion of the Mammalian Gene Collection (MGC)
Temple, Gary; Gerhard, Daniela S.; Rasooly, Rebekah; Feingold, Elise A.; Good, Peter J.; Robinson, Cristen; Mandich, Allison; Derge, Jeffrey G.; Lewis, Jeanne; Shoaf, Debonny; Collins, Francis S.; Jang, Wonhee; Wagner, Lukas; Shenmen, Carolyn M.; Misquitta, Leonie; Schaefer, Carl F.; Buetow, Kenneth H.; Bonner, Tom I.; Yankie, Linda; Ward, Ming; Phan, Lon; Astashyn, Alex; Brown, Garth; Farrell, Catherine; Hart, Jennifer; Landrum, Melissa; Maidak, Bonnie L.; Murphy, Michael; Murphy, Terence; Rajput, Bhanu; Riddick, Lillian; Webb, David; Weber, Janet; Wu, Wendy; Pruitt, Kim D.; Maglott, Donna; Siepel, Adam; Brejova, Brona; Diekhans, Mark; Harte, Rachel; Baertsch, Robert; Kent, Jim; Haussler, David; Brent, Michael; Langton, Laura; Comstock, Charles L.G.; Stevens, Michael; Wei, Chaochun; van Baren, Marijke J.; Salehi-Ashtiani, Kourosh; Murray, Ryan R.; Ghamsari, Lila; Mello, Elizabeth; Lin, Chenwei; Pennacchio, Christa; Schreiber, Kirsten; Shapiro, Nicole; Marsh, Amber; Pardes, Elizabeth; Moore, Troy; Lebeau, Anita; Muratet, Mike; Simmons, Blake; Kloske, David; Sieja, Stephanie; Hudson, James; Sethupathy, Praveen; Brownstein, Michael; Bhat, Narayan; Lazar, Joseph; Jacob, Howard; Gruber, Chris E.; Smith, Mark R.; McPherson, John; Garcia, Angela M.; Gunaratne, Preethi H.; Wu, Jiaqian; Muzny, Donna; Gibbs, Richard A.; Young, Alice C.; Bouffard, Gerard G.; Blakesley, Robert W.; Mullikin, Jim; Green, Eric D.; Dickson, Mark C.; Rodriguez, Alex C.; Grimwood, Jane; Schmutz, Jeremy; Myers, Richard M.; Hirst, Martin; Zeng, Thomas; Tse, Kane; Moksa, Michelle; Deng, Merinda; Ma, Kevin; Mah, Diana; Pang, Johnson; Taylor, Greg; Chuah, Eric; Deng, Athena; Fichter, Keith; Go, Anne; Lee, Stephanie; Wang, Jing; Griffith, Malachi; Morin, Ryan; Moore, Richard A.; Mayo, Michael; Munro, Sarah; Wagner, Susan; Jones, Steven J.M.; Holt, Robert A.; Marra, Marco A.; Lu, Sun; Yang, Shuwei; Hartigan, James; Graf, Marcus; Wagner, Ralf; Letovksy, Stanley; Pulido, Jacqueline C.; Robison, Keith; Esposito, Dominic; Hartley, James; Wall, Vanessa E.; Hopkins, Ralph F.; Ohara, Osamu; Wiemann, Stefan
2009-01-01
Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis. The MGC now contains clones with the entire protein-coding sequence for 92% of human and 89% of mouse genes with curated RefSeq (NM-accession) transcripts, and for 97% of human and 96% of mouse genes with curated RefSeq transcripts that have one or more PubMed publications, in addition to clones for more than 6300 rat genes. These high-quality MGC clones and their sequences are accessible without restriction to researchers worldwide. PMID:19767417
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It Takes A 'Village of Partnerships' To Raise A 'Big Data Facility' In A 'Big Data World'.
Evans, B. J. K.; Wyborn, L. A.
2015-12-01
The National Computational Infrastructure (NCI) at the Australian National University (ANU) has collocated a priority set of national and international data assets that span a wide range of domains from climate, oceans, geophysics, environment, astronomy, bioinformatics and the social sciences. The data are located on a 10 PB High Performance Data (HPD) Node that is integrated with a High Performance Computing (HPC) facility to enable a new style of Data-intensive in-situ analysis. Investigators can either log in via direct access to the data collections: access is also provided via modern standards-based web services. The NCI integrated HPD/HPC facility is supported by a 'village' of partnerships. NCI itself operates as a formal partnership between the ANU and three major National Scientific Agencies: CSIRO, the Bureau of Meteorology (BoM) and Geoscience Australia (GA). These same agencies are also the custodians of many of the national data collections hosted at NCI, and in partnership with other collaborating national and overseas organisations have agreed to work together to develop a shared data environment and use standards that enable interoperability between the collections, rather than isolating their collections as separate entities that each agency runs independently. To effectively analyse these complex and large volume data sets, NCI has entered into a series of national and national partnerships with international agencies to provide world-class digital analytical environments that allow computational to be conducted and shared. The ability for government and research to work in partnership at the NCI has been well established over the last decade, mainly with BoM, CSIRO, and GA. New emerging industry linkages are now being encouraged by revised government agendas and these promises to foster a new series of partnerships that will increase uptake of this major government funded infrastructure and promise to foster further collaboration and innovation.
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2013-09-10
...; 30-Day Comment Request: Awareness and Beliefs About Cancer Survey, National Cancer Institute (NCI.... Proposed Collection: Awareness and Beliefs about Cancer Survey, 0925-NEW, National Cancer Institute (NCI... gather data about American adults' awareness and beliefs about cancer. The ultimate goal is to determine...
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2011-07-01
...; Comment Request; Food Reporting Comparison Study (FORCS) and Food and Eating Assessment Study (FEAST) (NCI... Collection: Title: Food Reporting Comparison Study (FORCS) and Food and Eating Assessment Study (FEAST) (NCI... (in Minnesota, California, and Michigan) between ages 20 and 70 years. For the FEAST study...
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Arlt, Volker M; Gingerich, John; Schmeiser, Heinz H; Phillips, David H; Douglas, George R; White, Paul A
2008-11-01
FE1 lung epithelial cells derived from MutaMouse are a new model system to provide in vitro mutagenicity data with the potential to predict the outcome of an in vivo MutaMouse test. 3-Nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust and urban air pollution. We investigated the mutagenicity and DNA binding of 3-NBA and its main metabolite 3-aminobenzanthrone (3-ABA) in vitro and in vivo in the MutaMouse assay. Mice were treated with 3-NBA or 3-ABA (0, 2 or 5 mg/kg body weight/day) by gavage for 28 days and 28 days later lacZ mutant frequency (MF) was determined in liver, lung and bone marrow. For both compounds, dose-related increases in MF were seen in liver and bone marrow, but not in lung; mutagenic activity was approximately 2-fold lower for 3-ABA than for 3-NBA. With 3-NBA, highest DNA adduct levels (measured by (32)P-post-labelling) were found in liver (approximately 230 adducts per 10(8) nucleotides) with levels 20- to 40-fold lower in bone marrow and lung. With 3-ABA, DNA adduct levels were again highest in the liver, but approximately 4-fold lower than for 3-NBA. FE1 cells were exposed to up to 10 microg/ml 3-NBA or 3-ABA for 6 h with or without exogenous activation (S9) and harvested after 3 days. For 3-NBA, there was a dose-related increase in MF both with and without S9 mix, which was >10 times higher than observed in vivo. At the highest concentration of 3-ABA (10 microg/ml), we found only around a 2-fold increase in MF relative to controls. DNA adduct formation in FE1 cells was dose-dependent for both compounds, but 10- to 20-fold higher for 3-NBA compared to 3-ABA. Collectively, our data indicate that MutaMouse FE1 cells are well suited for cost-effective testing of suspected mutagens with different metabolic activation pathways as a guide for subsequent in vivo MutaMouse testing.
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Development of mPMab-1, a Mouse-Rat Chimeric Antibody Against Mouse Podoplanin.
Yamada, Shinji; Kaneko, Mika K; Nakamura, Takuro; Ichii, Osamu; Konnai, Satoru; Kato, Yukinari
2017-04-01
Podoplanin (PDPN), the ligand of C-type lectin-like receptor-2, is used as a lymphatic endothelial marker. We previously established clone PMab-1 of rat IgG 2a as a specific monoclonal antibody (mAb) against mouse PDPN. PMab-1 is also very sensitive in immunohistochemical analysis; however, rat mAbs seem to be unfavorable for pathologists because anti-mouse IgG and anti-rabbit IgG are usually used as secondary antibodies in commercially available kits for immunohistochemical analysis. In this study, we develop a mouse-rat chimeric antibody, mPMab-1 of mouse IgG 2a , which was derived from rat PMab-1 mAb. Immunohistochemical analysis shows that mPMab-1 detects podocytes of the kidney, lymphatic endothelial cells of the colon, and type I alveolar cells of the lung. Importantly, mPMab-1 is more sensitive than PMab-1. This conversion strategy from rat mAb to mouse mAb could be applicable to other mAbs.
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DEFF Research Database (Denmark)
Mateo, Julio C.; San Agustin, Javier; Hansen, John Paulin
2008-01-01
Facial EMG for selection is fast, easy and, combined with gaze pointing, it can provide completely hands-free interaction. In this pilot study, 5 participants performed a simple point-and-select task using mouse or gaze for pointing and a mouse button or a facial-EMG switch for selection. Gaze...
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A transcription factor collective defines the HSN serotonergic neuron regulatory landscape.
Lloret-Fernández, Carla; Maicas, Miren; Mora-Martínez, Carlos; Artacho, Alejandro; Jimeno-Martín, Ángela; Chirivella, Laura; Weinberg, Peter; Flames, Nuria
2018-03-22
Cell differentiation is controlled by individual transcription factors (TFs) that together activate a selection of enhancers in specific cell types. How these combinations of TFs identify and activate their target sequences remains poorly understood. Here, we identify the cis -regulatory transcriptional code that controls the differentiation of serotonergic HSN neurons in Caenorhabditis elegans . Activation of the HSN transcriptome is directly orchestrated by a collective of six TFs. Binding site clusters for this TF collective form a regulatory signature that is sufficient for de novo identification of HSN neuron functional enhancers. Among C. elegans neurons, the HSN transcriptome most closely resembles that of mouse serotonergic neurons. Mouse orthologs of the HSN TF collective also regulate serotonergic differentiation and can functionally substitute for their worm counterparts which suggests deep homology. Our results identify rules governing the regulatory landscape of a critically important neuronal type in two species separated by over 700 million years. © 2018, Lloret-Fernández et al.
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Comparative metabonomics of differential hydrazine toxicity in the rat and mouse
International Nuclear Information System (INIS)
Bollard, Mary E.; Keun, Hector C.; Beckonert, Olaf; Ebbels, Tim M.D.; Antti, Henrik; Nicholls, Andrew W.; Shockcor, John P.; Cantor, Glenn H.; Stevens, Greg; Lindon, John C.; Holmes, Elaine; Nicholson, Jeremy K.
2005-01-01
Interspecies variation between rats and mice has been studied for hydrazine toxicity using a novel metabonomics approach. Hydrazine hydrochloride was administered to male Sprague-Dawley rats (30 mg/kg, n = 10 and 90 mg/kg, n = 10) and male B6C3F mice (100 mg/kg, n = 8 and 250 mg/kg, n = 8) by oral gavage. In each species, the high dose was selected to produce the major histopathologic effect, hepatocellular lipid accumulation. Urine samples were collected at sequential time points up to 168 h post dose and analyzed by 1 H NMR spectroscopy. The metabolites of hydrazine, namely diacetyl hydrazine and 1,4,5,6-tetrahydro-6-oxo-3-pyridazine carboxylic acid (THOPC), were detected in both the rat and mouse urine samples. Monoacetyl hydrazine was detected only in urine samples from the rat and its absence in the urine of the mouse was attributed to a higher activity of N-acetyl transferases in the mouse compared with the rat. Differential metabolic effects observed between the two species included elevated urinary β-alanine, 3-D-hydroxybutyrate, citrulline, N-acetylcitrulline, and reduced trimethylamine-N-oxide excretion unique to the rat. Metabolic principal component (PC) trajectories highlighted the greater degree of toxic response in the rat. A data scaling method, scaled to maximum aligned and reduced trajectories (SMART) analysis, was used to remove the differences between the metabolic starting positions of the rat and mouse and varying magnitudes of effect, to facilitate comparison of the response geometries between the rat and mouse. Mice followed 'biphasic' open PC trajectories, with incomplete recovery 7 days after dosing, whereas rats followed closed 'hairpin' time profiles, indicating functional reversibility. The greater magnitude of metabolic effects observed in the rat was supported by the more pronounced effect on liver pathology in the rat when compared with the mouse
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2013-09-16
...; 30-day Comment Request: Family Life, Activity, Sun, Health, and Eating (FLASHE) Study (NCI) SUMMARY... Collection: Family Life, Activity, Sun, Health, and Eating (FLASHE) Study (NCI), 0925-NEW, Expiration Date xx... behaviors (but also examining other behaviors such as sleep, sun-safety, and tobacco) in new ways not...
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2012-04-13
... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Submission for OMB Review; Comment Request; Solar Cell: A Mobile UV Manager for Smart Phones Phase II (NCI) Summary: Under the... control number. Proposed Collection: Title: Solar Cell: A Mobile UV Manager for Smart Phones Phase II (NCI...
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International Nuclear Information System (INIS)
Roblin, R.O.; Bell, T.E.; Young, P.L.
1978-01-01
A sensitive, specific competition radioimmunoassay for mouse plasmin(ogen) has been developed in order to determine whether mouse tumor cells can synthesize plasminogen in vitro. The rabbit anti-BALB/c mouse plasminogen antibodies used in the assay react with the plasminogen present in serum from BALB/c, C3H, AKR and C57BL/6 mice, and also recognized mouse plasmin. The competition radiommunoassay can detect as little as 50 ng of mouse plasminogen. No competition was observed with preparations of fetal calf, human and rabbit plasminogens. A variety of virus-transformed and mouse tumor cell lines were all found to contain less than 100 ng mouse plasminogen/mg of cell extract protein. Thus, if the plasminogen activator/plasmin system is important in the growth or movement of this group of tumor cells, the cells will be dependent upon the circulatory system of the host for their plasminogen supply. (Auth.)
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Cano García, Elena
2013-01-01
L’estudi realitzat ha abordat quines són les competències i els factors clau que estudiants universitaris d’origen immigrant consideren que han estat claus per arribar a la universitat, assolint així l’èxit educatiu. S’han escollit estudiants que haguessin fet l’escolaritat obligatòria total o parcialment a Catalunya.Per dur a terme la recerca s’ha treballat amb relats de vida (un total de 13 escrits) i narracions audiovisuals (amb un total de 4 produccions), essent finalment 17 les evidèncie...
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Evaluation of perfluoroalkyl acid activity using primary mouse and human hepatocytes
International Nuclear Information System (INIS)
Rosen, Mitchell B.; Das, Kaberi P.; Wood, Carmen R.; Wolf, Cynthia J.; Abbott, Barbara D.; Lau, Christopher
2013-01-01
While perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been studied at length, less is known about the biological activity of other perfluoroalkyl acids (PFAAs) detected in the environment. Using a transient transfection assay developed in COS-1 cells, our group has previously evaluated a variety of PFAAs for activity associated with activation of peroxisome proliferator-activated receptor alpha (PPARα). Here we use primary heptatocytes to further assess the biological activity of a similar group of PFAAs using custom designed Taqman Low Density Arrays. Primary mouse and human hepatoyctes were cultured for 48 h in the presence of varying concentrations of 12 different PFAAs or Wy14,643, a known activator of PPARα. Total RNA was collected and the expression of 48 mouse or human genes evaluated. Gene selection was based on either in-house liver microarray data (mouse) or published data using primary hepatocytes (human). Gene expression in primary mouse hepatocytes was more restricted than expected. Genes typically regulated in whole tissue by PPARα agonists were not altered in mouse cells including Acox1, Me1, Acaa1a, Hmgcs1, and Slc27a1. Cyp2b10, a gene regulated by the constitutive androstane receptor and a transcript normally up-regulated by in vivo exposure to PFAAs, was also unchanged in cultured mouse hepatocytes. Cyp4a14, Ehhadh, Pdk4, Cpt1b, and Fabp1 were regulated as expected in mouse cells. A larger group of genes were differentially expressed in human primary hepatocytes, however, little consistency was observed across compounds with respect to which genes produced a significant dose response making the determination of relative biological activity difficult. This likely reflects weaker activation of PPARα in human versus rodent cells as well as variation among individual cell donors. Unlike mouse cells, CYP2B6 was up-regulated in human hepatocytes by a number of PFAAs as was PPARδ. Rankings were conducted on the limited
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Comparison of confocal microscopy and two-photon microscopy in mouse cornea in vivo.
Lee, Jun Ho; Lee, Seunghun; Gho, Yong Song; Song, In Seok; Tchah, Hungwon; Kim, Myoung Joon; Kim, Ki Hean
2015-03-01
High-resolution imaging of the cornea is important for studying corneal diseases at cellular levels. Confocal microscopy (CM) has been widely used in the clinic, and two-photon microscopy (TPM) has recently been introduced in various pre-clinical studies. We compared the performance of CM and TPM in normal mouse corneas and neovascularized mouse corneas induced by suturing. Balb/C mice and C57BL/6 mice expressing green fluorescent protein (GFP) were used to compare modalities based on intrinsic contrast and extrinsic fluorescence contrast. CM based on reflection (CMR), CM based on fluorescence (CMF), and TPM based on intrinsic/extrinsic fluorescence and second harmonic generation (SHG) were compared by imaging the same sections of mouse corneas sequentially in vivo. In normal mouse corneas, CMR visualized corneal cell morphologies with some background noise, and CMF visualized GFP expressing corneal cells clearly. TPM visualized corneal cells and collagen in the stroma based on fluorescence and SHG, respectively. However, in neovascularized mouse corneas, CMR could not resolve cells deep inside the cornea due to high background noise from the effects of increased structural irregularity induced by suturing. CMF and TPM visualized cells and induced vasculature better than CMR because both collect signals from fluorescent cells only. Both CMF and TPM had signal decays with depth due to the structural irregularity, with CMF having faster signal decay than TPM. CMR, CMF, and TPM showed different degrees of image degradation in neovascularized mouse corneas. Copyright © 2015 Elsevier Ltd. All rights reserved.
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The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer.
Krupke, Debra M; Begley, Dale A; Sundberg, John P; Richardson, Joel E; Neuhauser, Steven B; Bult, Carol J
2017-11-01
Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) database is an expertly curated, comprehensive compendium of mouse models of human cancer. Through the enforcement of nomenclature and related annotation standards, MTB supports aggregation of data about a cancer model from diverse sources and assessment of how genetic background of a mouse strain influences the biological properties of a specific tumor type and model utility. Cancer Res; 77(21); e67-70. ©2017 AACR . ©2017 American Association for Cancer Research.
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Koopmans, Bastijn; Smit, August B; Verhage, Matthijs; Loos, Maarten
2017-04-04
Systematic, standardized and in-depth phenotyping and data analyses of rodent behaviour empowers gene-function studies, drug testing and therapy design. However, no data repositories are currently available for standardized quality control, data analysis and mining at the resolution of individual mice. Here, we present AHCODA-DB, a public data repository with standardized quality control and exclusion criteria aimed to enhance robustness of data, enabled with web-based mining tools for the analysis of individually and group-wise collected mouse phenotypic data. AHCODA-DB allows monitoring in vivo effects of compounds collected from conventional behavioural tests and from automated home-cage experiments assessing spontaneous behaviour, anxiety and cognition without human interference. AHCODA-DB includes such data from mutant mice (transgenics, knock-out, knock-in), (recombinant) inbred strains, and compound effects in wildtype mice and disease models. AHCODA-DB provides real time statistical analyses with single mouse resolution and versatile suite of data presentation tools. On March 9th, 2017 AHCODA-DB contained 650 k data points on 2419 parameters from 1563 mice. AHCODA-DB provides users with tools to systematically explore mouse behavioural data, both with positive and negative outcome, published and unpublished, across time and experiments with single mouse resolution. The standardized (automated) experimental settings and the large current dataset (1563 mice) in AHCODA-DB provide a unique framework for the interpretation of behavioural data and drug effects. The use of common ontologies allows data export to other databases such as the Mouse Phenome Database. Unbiased presentation of positive and negative data obtained under the highly standardized screening conditions increase cost efficiency of publicly funded mouse screening projects and help to reach consensus conclusions on drug responses and mouse behavioural phenotypes. The website is publicly
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Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome.
de Souza, Fabio M Simoes; Busquet, Nicolas; Blatner, Megan; Maclean, Kenneth N; Restrepo, Diego
2011-01-01
Down syndrome (DS) is the most common form of congenital intellectual disability. Although DS involves multiple disturbances in various tissues, there is little doubt that in terms of quality of life cognitive impairment is the most serious facet and there is no effective treatment for this aspect of the syndrome. The Ts65Dn mouse model of DS recapitulates multiple aspects of DS including cognitive impairment. Here the Ts65Dn mouse model of DS was evaluated in an associative learning paradigm based on olfactory cues. In contrast to disomic controls, trisomic mice exhibited significant deficits in olfactory learning. Treatment of trisomic mice with the acetylcholinesterase inhibitor galantamine resulted in a significant improvement in olfactory learning. Collectively, our study indicates that olfactory learning can be a sensitive tool for evaluating deficits in associative learning in mouse models of DS and that galantamine has therapeutic potential for improving cognitive abilities.
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2004-09-01
Astronomers have used an X-ray image to make the first detailed study of the behavior of high-energy particles around a fast moving pulsar. The image, from NASA's Chandra X-ray Observatory, shows the shock wave created as a pulsar plows supersonically through interstellar space. These results will provide insight into theories for the production of powerful winds of matter and antimatter by pulsars. Chandra's image of the glowing cloud, known as the Mouse, shows a stubby bright column of high-energy particles, about four light years in length, swept back by the pulsar's interaction with interstellar gas. The intense source at the head of the X-ray column is the pulsar, estimated to be moving through space at about 1.3 million miles per hour. VLA Radio Image of the Mouse, Full Field VLA Radio Image of the Mouse, Full Field A cone-shaped cloud of radio-wave-emitting particles envelopes the X-ray column. The Mouse, a.k.a. G359.23-0.82, was discovered in 1987 by radio astronomers using the National Science Foundation's Very Large Array in New Mexico. It gets its name from its appearance in radio images that show a compact snout, a bulbous body, and a remarkable long, narrow, tail that extends for about 55 light years. "A few dozen pulsar wind nebulae are known, including the spectacular Crab Nebula, but none have the Mouse's combination of relatively young age and incredibly rapid motion through interstellar space," said Bryan Gaensler of the Harvard-Smithsonian Center for Astrophysics and lead author of a paper on the Mouse that will appear in an upcoming issue of The Astrophysical Journal. "We effectively are seeing a supersonic cosmic wind tunnel, in which we can study the effects of a pulsar's motion on its pulsar wind nebula, and test current theories." Illustration of the Mouse System Illustration of the Mouse System Pulsars are known to be rapidly spinning, highly magnetized neutron stars -- objects so dense that a mass equal to that of the Sun is packed into a
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Genetic Dissection of Trabecular Bone Structure with Mouse Intersubspecific Consomic Strains
Directory of Open Access Journals (Sweden)
Taro Kataoka
2017-10-01
Full Text Available Trabecular bone structure has an important influence on bone strength, but little is known about its genetic regulation. To elucidate the genetic factor(s regulating trabecular bone structure, we compared the trabecular bone structures of two genetically remote mouse strains, C57BL/6J and Japanese wild mouse-derived MSM/Ms. Phenotyping by X-ray micro-CT revealed that MSM/Ms has structurally more fragile trabecular bone than C57BL/6J. Toward identification of genetic determinants for the difference in fragility of trabecular bone between the two mouse strains, we employed phenotype screening of consomic mouse strains in which each C57BL/6J chromosome is substituted by its counterpart from MSM/Ms. The results showed that many chromosomes affect trabecular bone structure, and that the consomic strain B6-Chr15MSM, carrying MSM/Ms-derived chromosome 15 (Chr15, has the lowest values for the parameters BV/TV, Tb.N, and Conn.D, and the highest values for the parameters Tb.Sp and SMI. Subsequent phenotyping of subconsomic strains for Chr15 mapped four novel trabecular bone structure-related QTL (Tbsq1-4 on mouse Chr15. These results collectively indicate that genetic regulation of trabecular bone structure is highly complex, and that even in the single Chr15, the combined action of the four Tbsqs controls the fragility of trabecular bone. Given that Tbsq4 is syntenic to human Chr 12q12-13.3, where several bone-related SNPs are assigned, further study of Tbsq4 should facilitate our understanding of the genetic regulation of bone formation in humans.
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DEFF Research Database (Denmark)
Calum, Henrik; Høiby, Niels; Moser, Claus
2014-01-01
Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third-degree b......Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third...... with infected burn wound compared with the burn wound only group. The burn mouse model resembles the clinical situation and provides an opportunity to examine or develop new strategies like new antibiotics and immune therapy, in handling burn wound victims much....
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A Transgenic Tri-Modality Reporter Mouse
Yan, Xinrui; Ray, Pritha; Paulmurugan, Ramasamy; Tong, Ricky; Gong, Yongquan; Sathirachinda, Ataya; Wu, Joseph C.; Gambhir, Sanjiv S.
2013-01-01
Transgenic mouse with a stably integrated reporter gene(s) can be a valuable resource for obtaining uniformly labeled stem cells, tissues, and organs for various applications. We have generated a transgenic mouse model that ubiquitously expresses a tri-fusion reporter gene (fluc2-tdTomato-ttk) driven by a constitutive chicken β-actin promoter. This "Tri-Modality Reporter Mouse" system allows one to isolate most cells from this donor mouse and image them for bioluminescent (fluc2), fluorescent...
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Proteomic interactions in the mouse vitreous-retina complex.
Directory of Open Access Journals (Sweden)
Jessica M Skeie
Full Text Available Human vitreoretinal diseases are due to presumed abnormal mechanical interactions between the vitreous and retina, and translational models are limited. This study determined whether nonstructural proteins and potential retinal biomarkers were expressed by the normal mouse vitreous and retina.Vitreous and retina samples from mice were collected by evisceration and analyzed by liquid chromatography-tandem mass spectrometry. Identified proteins were further analyzed for differential expression and functional interactions using bioinformatic software.We identified 1,680 unique proteins in the retina and 675 unique proteins in the vitreous. Unbiased clustering identified protein pathways that distinguish retina from vitreous including oxidative phosphorylation and neurofilament cytoskeletal remodeling, whereas the vitreous expressed oxidative stress and innate immunology pathways. Some intracellular protein pathways were found in both retina and vitreous, such as glycolysis and gluconeogenesis and neuronal signaling, suggesting proteins might be shuttled between the retina and vitreous. We also identified human disease biomarkers represented in the mouse vitreous and retina, including carbonic anhydrase-2 and 3, crystallins, macrophage inhibitory factor, glutathione peroxidase, peroxiredoxins, S100 precursors, and von Willebrand factor.Our analysis suggests the vitreous expresses nonstructural proteins that functionally interact with the retina to manage oxidative stress, immune reactions, and intracellular proteins may be exchanged between the retina and vitreous. This novel proteomic dataset can be used for investigating human vitreoretinopathies in mouse models. Validation of vitreoretinal biomarkers for human ocular diseases will provide a critical tool for diagnostics and an avenue for therapeutics.
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Proteomic interactions in the mouse vitreous-retina complex.
Skeie, Jessica M; Mahajan, Vinit B
2013-01-01
Human vitreoretinal diseases are due to presumed abnormal mechanical interactions between the vitreous and retina, and translational models are limited. This study determined whether nonstructural proteins and potential retinal biomarkers were expressed by the normal mouse vitreous and retina. Vitreous and retina samples from mice were collected by evisceration and analyzed by liquid chromatography-tandem mass spectrometry. Identified proteins were further analyzed for differential expression and functional interactions using bioinformatic software. We identified 1,680 unique proteins in the retina and 675 unique proteins in the vitreous. Unbiased clustering identified protein pathways that distinguish retina from vitreous including oxidative phosphorylation and neurofilament cytoskeletal remodeling, whereas the vitreous expressed oxidative stress and innate immunology pathways. Some intracellular protein pathways were found in both retina and vitreous, such as glycolysis and gluconeogenesis and neuronal signaling, suggesting proteins might be shuttled between the retina and vitreous. We also identified human disease biomarkers represented in the mouse vitreous and retina, including carbonic anhydrase-2 and 3, crystallins, macrophage inhibitory factor, glutathione peroxidase, peroxiredoxins, S100 precursors, and von Willebrand factor. Our analysis suggests the vitreous expresses nonstructural proteins that functionally interact with the retina to manage oxidative stress, immune reactions, and intracellular proteins may be exchanged between the retina and vitreous. This novel proteomic dataset can be used for investigating human vitreoretinopathies in mouse models. Validation of vitreoretinal biomarkers for human ocular diseases will provide a critical tool for diagnostics and an avenue for therapeutics.
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Haemozoin Detection in Mouse Liver Histology Using Simple Polarized Light Microscope
Directory of Open Access Journals (Sweden)
DWI RAMADHANI
2014-03-01
Full Text Available The presence of malarial pigment (haemozoin due to Plasmodium infection is a common histopathological effect in mouse liver. Previous research showed that by using a polarized light microscope, researchers were better able to detect haemozoin in mouse liver histology section. Thus, the aim of this research was to compare the haemozoin area observed by a conventional vs. simple polarized light microscope by using image processing analysis. A total of 40 images produced from both conventional light microscope and simple polarized light microscope were collected. All images were analyzed using ImageJ 1.47 software to measure the haemozoin areas. Our results showed that non birefringent haemozoin and birefringent haemozoin area was significantly different. This was because when using conventional light microscope the brown area that contained images of non birefringent haemozoin images also contained Kupffer cells which appeared as the same brown color as haemozoin. In contrast, haemozoin gave bright effect and can be easily differentiated with Kupffer cells in the birefringent haemozoin images. This study concluded that haemozoin detection in mouse liver histology using a simple polarized light microscope was more accurate compared to that of conventional light microscope.
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Directory of Open Access Journals (Sweden)
Javier Fombona Cadavieco
2012-12-01
Full Text Available Aquesta investigació analitza la percepció de l'estudiant universitari sobre els beneficis de la mobilitat estudiantil en l'Espai Europeu d'Educació Superior. Especialment atenem a l'anàlisi de competències genèriques que puguin atorgar més possibilitats en la recerca d'ocupació. Per això, abordem un estudi de casos a la Universitat d'Oviedo des d'una metodologia quantitativa prenent com a referència els objectius marcats en la iniciativa Europa 2020. Les conclusions donen resultats molt positius en competències interdisciplinars per a la recerca de feina, com ara el domini idiomàtic, el coneixement de noves societats i dels entorns professionals.
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International Nuclear Information System (INIS)
Hahn, S; Jaffray, D; Chetty, I; Benedict, S
2014-01-01
Radiotherapy is one of the most effective treatments for solid tumors, in large part due to significant technological advances associated with, for instance, the ability to target tumors to very high levels of accuracy (within millimeters). Technological advances have played a central role in the success of radiation therapy as an oncologic treatment option for patients. ASTRO, AAPM and NCI sponsored a workshop “Technology for Innovation in Radiation Oncology” at the NCI campus in Bethesda, MD on June 13–14, 2013. The purpose of this workshop was to bring together expert clinicians and scientists to discuss the role of disruptive technologies in radiation oncology, in particular with regard to how they are being developed and translated to clinical practice in the face of current and future challenges and opportunities. The technologies discussed encompassed imaging and delivery aspects, along with methods to enable/facilitate application of them in the clinic. Measures for assessment of the performance of these technologies, such as techniques to validate quantitative imaging, were reviewed. Novel delivery technologies, incorporating efficient and safe delivery mechanisms enabled by development of tools for process automation and the associated field of oncology informatics formed one of the central themes of the workshop. The discussion on disruptive technologies was grounded in the need for evidence of efficacy. Scientists in the areas of technology assessment and bioinformatics provided expert views on different approaches toward evaluation of technology efficacy. Clinicians well versed in clinical trials incorporating disruptive technologies (e.g. SBRT for early stage lung cancer) discussed the important role of these technologies in significantly improving local tumor control and survival for these cohorts of patients. Recommendations summary focused on the opportunities associated with translating the technologies into the clinic and assessing their
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Energy Technology Data Exchange (ETDEWEB)
Hahn, S [University of Pennsylvania, Philadelphia, PA (United States); Jaffray, D [Princess Margaret Hospital, Toronto, ON (Canada); Chetty, I [Henry Ford Health System, Detroit, MI (United States); Benedict, S [UC Davis Cancer Center, Sacramento, CA (United States)
2014-06-15
Radiotherapy is one of the most effective treatments for solid tumors, in large part due to significant technological advances associated with, for instance, the ability to target tumors to very high levels of accuracy (within millimeters). Technological advances have played a central role in the success of radiation therapy as an oncologic treatment option for patients. ASTRO, AAPM and NCI sponsored a workshop “Technology for Innovation in Radiation Oncology” at the NCI campus in Bethesda, MD on June 13–14, 2013. The purpose of this workshop was to bring together expert clinicians and scientists to discuss the role of disruptive technologies in radiation oncology, in particular with regard to how they are being developed and translated to clinical practice in the face of current and future challenges and opportunities. The technologies discussed encompassed imaging and delivery aspects, along with methods to enable/facilitate application of them in the clinic. Measures for assessment of the performance of these technologies, such as techniques to validate quantitative imaging, were reviewed. Novel delivery technologies, incorporating efficient and safe delivery mechanisms enabled by development of tools for process automation and the associated field of oncology informatics formed one of the central themes of the workshop. The discussion on disruptive technologies was grounded in the need for evidence of efficacy. Scientists in the areas of technology assessment and bioinformatics provided expert views on different approaches toward evaluation of technology efficacy. Clinicians well versed in clinical trials incorporating disruptive technologies (e.g. SBRT for early stage lung cancer) discussed the important role of these technologies in significantly improving local tumor control and survival for these cohorts of patients. Recommendations summary focused on the opportunities associated with translating the technologies into the clinic and assessing their
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Identification of phosphoproteins coupled to initiation of motility in live epididymal mouse sperm
Tash, J. S.; Bracho, G. E.
1998-01-01
A method for collecting live immotile cauda epididymal mouse sperm that initiate motility by dilution into an activation buffer is described. Sperm in collection buffer showed low percent motility (MOT) and population progression (PRG) that increased 10-fold and 9-fold, respectively, during the first 2 min after dilution into activation buffer. Western phosphoserine (pS), phosphothreonine (pT), and phosphotyrosine (pY) analysis revealed a 120 kDa protein that markedly increased in pT content during initiation of motility and may be related to FP130, the motility-coupled axonemal protein of sea urchin sperm. A prominent 82 kDa protein that was pS and pT-phosphorylated in immotile and motile sperm is likely the fibrous sheath component AKAP82 that is phosphorylated during spermatogenesis. Analysis of live human sperm also identified a prominent 120 kDa pT protein. Thus it appears that phosphorylation of FP130 and related 120 kDa proteins in mouse, and perhaps human sperm, represent common targets during motility initiation in sperm. Copyright 1998 Academic Press.
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Genetic control of resistance to Trypanosoma brucei brucei infection in mice
Czech Academy of Sciences Publication Activity Database
Šíma, Matyáš; Havelková, Helena; Quan, L.; Svobodová, M.; Jarošíková, T.; Vojtíšková, Jarmila; Stassen, A. P. M.; Demant, P.; Lipoldová, Marie
2011-01-01
Roč. 5, č. 6 (2011), e1173 ISSN 1935-2735 R&D Projects: GA AV ČR IAA500520606; GA MŠk(CZ) LC06009 Grant - others:NIH-NCI(US) 1R01CA127162-01 Institutional research plan: CEZ:AV0Z50520514 Keywords : Trypanosoma brucei brucei * mouse recombinant congenic strains * Tbbr Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.716, year: 2011
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Flavonoid Composition and Antitumor Activity of Bee Bread Collected in Northeast Portugal
Directory of Open Access Journals (Sweden)
Filipa Sobral
2017-02-01
Full Text Available Bee bread (BB is a fermented mixture of plant pollen, honey, and bee saliva that worker bees use as food for larvae, and for young bees to produce royal jelly. In the present study, five BB samples, collected from Apis mellifera iberiensis hives located in different apiaries near Bragança, in the northeast region of Portugal, and one BB commercial sample were characterized by high-performance liquid chromatography coupled to a diode array detector and electrospray mass spectrometry (HPLC-DAD-ESI/MS in terms of phenolic compounds, such as flavonoid glycoside derivatives. Furthermore, the samples were screened, using in vitro assays, against different human tumor cell lines, MCF-7 (breast adenocarcinoma, NCI-H460 (non-small cell lung cancer, HeLa (cervical carcinoma and HepG2 (hepatocellular carcinoma, and also against non-tumor liver cells (porcine liver cells, PLP2. The main phenolic compounds found were flavonol derivatives, mainly quercetin, kaempferol, myricetin, isorhamnetin and herbacetrin glycoside derivatives. Thirty-two compounds were identified in the six BB samples, presenting BB1 and BB3 with the highest contents (6802 and 6480 µg/g extract, respectively and the highest number of identified compounds. Two isorhamnetin glycoside derivatives, isrohamnetin-O-hexosyl-O-rutinoside and isorhamnetin-O-pentosyl-hexoside, were the most abundant compounds present in BB1; on the other hand, quercetin-3-O-rhamnoside was the most abundant flavonol in BB3. However, it was not possible to establish a correlation between the flavonoids and the observed low to moderate cytotoxicity (ranging from >400 to 68 µg/mL, in which HeLa and NCI-H460 cell lines were the most susceptible to the inhibition. To the authors’ knowledge, this is the first report characterizing glycosidic flavonoids in BB samples, contributing to the chemical knowledge of this less explored bee product.
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Recommendations for Collection and Handling of Specimens From Group Breast Cancer Clinical Trials
Leyland-Jones, Brian R.; Ambrosone, Christine B.; Bartlett, John; Ellis, Matthew J.C.; Enos, Rebecca A.; Raji, Adekunle; Pins, Michael R.; Zujewski, Jo Anne; Hewitt, Stephen M.; Forbes, John F.; Abramovitz, Mark; Braga, Sofia; Cardoso, Fatima; Harbeck, Nadia; Denkert, Carsten; Jewell, Scott D.
2008-01-01
Recommendations for specimen collection and handling have been developed for adoption across breast cancer clinical trials conducted by the Breast International Group (BIG)-sponsored Groups and the National Cancer Institute (NCI)-sponsored North American Cooperative Groups. These recommendations are meant to promote identifiable standards for specimen collection and handling within and across breast cancer trials, such that the variability in collection/handling practices that currently exists is minimized and specimen condition and quality are enhanced, thereby maximizing results from specimen-based diagnostic testing and research. Three working groups were formed from the Cooperative Group Banking Committee, BIG groups, and North American breast cancer cooperative groups to identify standards for collection and handling of (1) formalin-fixed, paraffin-embedded (FFPE) tissue; (2) blood and its components; and (3) fresh/frozen tissue from breast cancer trials. The working groups collected standard operating procedures from multiple group specimen banks, administered a survey on banking practices to those banks, and engaged in a series of discussions from 2005 to 2007. Their contributions were synthesized into this document, which focuses primarily on collection and handling of specimens to the point of shipment to the central bank, although also offers some guidance to central banks. Major recommendations include submission of an FFPE block, whole blood, and serial serum or plasma from breast cancer clinical trials, and use of one fixative and buffer type (10% neutral phosphate-buffered formalin, pH 7) for FFPE tissue across trials. Recommendations for proper handling and shipping were developed for blood, serum, plasma, FFPE, and fresh/frozen tissue. PMID:18955459
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Ali, A; Fahmy, S
2007-07-01
The objective was to evaluate ovarian dynamics and progesterone concentrations in cyclic (CYC, n=10) and non-cyclic (NCY, n=8) buffalo-cows during Ovsynch program. All cows received GnRH on day 0, PGF2alpha on day 7, and GnRH on day 9, and AI 14 h later. Ovarian structures were monitored by ultrasound and milk samples were collected for progesterone (P4) analysis. The first GnRH resulted in ovulation in CYC (90%) and NCY (62.5%) cows. By day 7, almost all cows had large follicle and lutein tissue. Luteolytic responses to PGF2alpha were 80 and 87.5% for CYC and NCY cows, respectively. Following second GnRH, ovulation occurred in 80% of CYC and 100% of NCY cows. Ovulation began earlier (12 h following second GnRH) and extended for longer (36 h) in NCY cows, when compared to CYC cows (36 and 12 h, respectively). The mean P4 levels increased from days 0 through 7 in CYC and NCY cows and levels were higher in CYC group. Conception rates were 60 and 37.5% in CYC and NYC cows, respectively. Early and asynchronous ovulation and luteal sub-function seemed to be a problem in NCY cows. Inseminating NCY cows twice, at 0 and 24 h of the second GnRH is recommended.
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Wickremsinhe, Enaksha R; Perkins, Everett J
2015-01-01
Traditional pharmacokinetic analysis in nonclinical studies is based on the concentration of a test compound in plasma and requires approximately 100 to 200 µL blood collected per time point. However, the total blood volume of mice limits the number of samples that can be collected from an individual animal—often to a single collection per mouse—thus necessitating dosing multiple mice to generate a pharmacokinetic profile in a sparse-sampling design. Compared with traditional methods, dried blood spot (DBS) analysis requires smaller volumes of blood (15 to 20 µL), thus supporting serial blood sampling and the generation of a complete pharmacokinetic profile from a single mouse. Here we compare plasma-derived data with DBS-derived data, explain how to adopt DBS sampling to support discovery mouse studies, and describe how to generate pharmacokinetic and pharmacodynamic data from a single mouse. Executing novel study designs that use DBS enhances the ability to identify and streamline better drug candidates during drug discovery. Implementing DBS sampling can reduce the number of mice needed in a drug discovery program. In addition, the simplicity of DBS sampling and the smaller numbers of mice needed translate to decreased study costs. Overall, DBS sampling is consistent with 3Rs principles by achieving reductions in the number of animals used, decreased restraint-associated stress, improved data quality, direct comparison of interanimal variability, and the generation of multiple endpoints from a single study. PMID:25836959
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Dowell, Karen G; Simons, Allen K; Bai, Hao; Kell, Braden; Wang, Zack Z; Yun, Kyuson; Hibbs, Matthew A
2014-05-01
Embryonic stem cells (ESCs), characterized by their ability to both self-renew and differentiate into multiple cell lineages, are a powerful model for biomedical research and developmental biology. Human and mouse ESCs share many features, yet have distinctive aspects, including fundamental differences in the signaling pathways and cell cycle controls that support self-renewal. Here, we explore the molecular basis of human ESC self-renewal using Bayesian network machine learning to integrate cell-type-specific, high-throughput data for gene function discovery. We integrated high-throughput ESC data from 83 human studies (~1.8 million data points collected under 1,100 conditions) and 62 mouse studies (~2.4 million data points collected under 1,085 conditions) into separate human and mouse predictive networks focused on ESC self-renewal to analyze shared and distinct functional relationships among protein-coding gene orthologs. Computational evaluations show that these networks are highly accurate, literature validation confirms their biological relevance, and reverse transcriptase polymerase chain reaction (RT-PCR) validation supports our predictions. Our results reflect the importance of key regulatory genes known to be strongly associated with self-renewal and pluripotency in both species (e.g., POU5F1, SOX2, and NANOG), identify metabolic differences between species (e.g., threonine metabolism), clarify differences between human and mouse ESC developmental signaling pathways (e.g., leukemia inhibitory factor (LIF)-activated JAK/STAT in mouse; NODAL/ACTIVIN-A-activated fibroblast growth factor in human), and reveal many novel genes and pathways predicted to be functionally associated with self-renewal in each species. These interactive networks are available online at www.StemSight.org for stem cell researchers to develop new hypotheses, discover potential mechanisms involving sparsely annotated genes, and prioritize genes of interest for experimental validation
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Mouse SNP Miner: an annotated database of mouse functional single nucleotide polymorphisms
Directory of Open Access Journals (Sweden)
Ramensky Vasily E
2007-01-01
Full Text Available Abstract Background The mapping of quantitative trait loci in rat and mouse has been extremely successful in identifying chromosomal regions associated with human disease-related phenotypes. However, identifying the specific phenotype-causing DNA sequence variations within a quantitative trait locus has been much more difficult. The recent availability of genomic sequence from several mouse inbred strains (including C57BL/6J, 129X1/SvJ, 129S1/SvImJ, A/J, and DBA/2J has made it possible to catalog DNA sequence differences within a quantitative trait locus derived from crosses between these strains. However, even for well-defined quantitative trait loci ( Description To help identify functional DNA sequence variations within quantitative trait loci we have used the Ensembl annotated genome sequence to compile a database of mouse single nucleotide polymorphisms (SNPs that are predicted to cause missense, nonsense, frameshift, or splice site mutations (available at http://bioinfo.embl.it/SnpApplet/. For missense mutations we have used the PolyPhen and PANTHER algorithms to predict whether amino acid changes are likely to disrupt protein function. Conclusion We have developed a database of mouse SNPs predicted to cause missense, nonsense, frameshift, and splice-site mutations. Our analysis revealed that 20% and 14% of missense SNPs are likely to be deleterious according to PolyPhen and PANTHER, respectively, and 6% are considered deleterious by both algorithms. The database also provides gene expression and functional annotations from the Symatlas, Gene Ontology, and OMIM databases to further assess candidate phenotype-causing mutations. To demonstrate its utility, we show that Mouse SNP Miner successfully finds a previously identified candidate SNP in the taste receptor, Tas1r3, that underlies sucrose preference in the C57BL/6J strain. We also use Mouse SNP Miner to derive a list of candidate phenotype-causing mutations within a previously
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Steroid metabolism in the mouse placenta
International Nuclear Information System (INIS)
Okker-Reitsma, G.H.
1976-01-01
The purpose of the study described in this thesis was to investigate the capacity for steroid synthesis of the mouse placenta - especially the production of progesterone, androgens and estrogens - and to determine, if possible, the relation of steroid synthesis to special cell types. In an introductory chapter the androgen production in the mouse placenta is surveyed by means of a histochemical and bioindicator study of different stages of development of the placenta. The metabolism of [ 3 H]-dehydroepiandrosterone and [ 3 H]-progesterone by mouse placental tissue in vitro is studied. The metabolism of [ 3 H]-progesterone by the mouse fetal adrenal in vitro is also studied
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Evaluation of synthetic vascular grafts in a mouse carotid grafting model.
Chan, Alex H P; Tan, Richard P; Michael, Praveesuda L; Lee, Bob S L; Vanags, Laura Z; Ng, Martin K C; Bursill, Christina A; Wise, Steven G
2017-01-01
Current animal models for the evaluation of synthetic grafts are lacking many of the molecular tools and transgenic studies available to other branches of biology. A mouse model of vascular grafting would allow for the study of molecular mechanisms of graft failure, including in the context of clinically relevant disease states. In this study, we comprehensively characterise a sutureless grafting model which facilitates the evaluation of synthetic grafts in the mouse carotid artery. Using conduits electrospun from polycaprolactone (PCL) we show the gradual development of a significant neointima within 28 days, found to be greatest at the anastomoses. Histological analysis showed temporal increases in smooth muscle cell and collagen content within the neointima, demonstrating its maturation. Endothelialisation of the PCL grafts, assessed by scanning electron microscopy (SEM) analysis and CD31 staining, was near complete within 28 days, together replicating two critical aspects of graft performance. To further demonstrate the potential of this mouse model, we used longitudinal non-invasive tracking of bone-marrow mononuclear cells from a transgenic mouse strain with a dual reporter construct encoding both luciferase and green fluorescent protein (GFP). This enabled characterisation of mononuclear cell homing and engraftment to PCL using bioluminescence imaging and histological staining over time (7, 14 and 28 days). We observed peak luminescence at 7 days post-graft implantation that persisted until sacrifice at 28 days. Collectively, we have established and characterised a high-throughput model of grafting that allows for the evaluation of key clinical drivers of graft performance.
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Evaluation of synthetic vascular grafts in a mouse carotid grafting model.
Directory of Open Access Journals (Sweden)
Alex H P Chan
Full Text Available Current animal models for the evaluation of synthetic grafts are lacking many of the molecular tools and transgenic studies available to other branches of biology. A mouse model of vascular grafting would allow for the study of molecular mechanisms of graft failure, including in the context of clinically relevant disease states. In this study, we comprehensively characterise a sutureless grafting model which facilitates the evaluation of synthetic grafts in the mouse carotid artery. Using conduits electrospun from polycaprolactone (PCL we show the gradual development of a significant neointima within 28 days, found to be greatest at the anastomoses. Histological analysis showed temporal increases in smooth muscle cell and collagen content within the neointima, demonstrating its maturation. Endothelialisation of the PCL grafts, assessed by scanning electron microscopy (SEM analysis and CD31 staining, was near complete within 28 days, together replicating two critical aspects of graft performance. To further demonstrate the potential of this mouse model, we used longitudinal non-invasive tracking of bone-marrow mononuclear cells from a transgenic mouse strain with a dual reporter construct encoding both luciferase and green fluorescent protein (GFP. This enabled characterisation of mononuclear cell homing and engraftment to PCL using bioluminescence imaging and histological staining over time (7, 14 and 28 days. We observed peak luminescence at 7 days post-graft implantation that persisted until sacrifice at 28 days. Collectively, we have established and characterised a high-throughput model of grafting that allows for the evaluation of key clinical drivers of graft performance.
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IN VITRO CULTURE OF FROZEN AND THAWED MOUSE OVA
KANAGAWA, Hiroshi
1980-01-01
Seventy mouse ova at the 4--8-cell stages were collected at room temperature from mice treated with pregnant mare's serum gonadotrophin and human chorionic gonadotrophin. Seventy ova were divided into 5 groups, and each group was placed in a 0.5 ml plastic straw with 0.2 ml of Brinster's medium. Then, the straws were immersed into an ice bath (0℃) for 5 minutes. Next, an equal volume of 2 M dimethyl sulfoxide was added to the sample straw. The medium with ova was then seeded at -6℃ and cooled...
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Law, MeiYee; Shaw, David R
2018-01-01
Mouse Genome Informatics (MGI, http://www.informatics.jax.org/ ) web resources provide free access to meticulously curated information about the laboratory mouse. MGI's primary goal is to help researchers investigate the genetic foundations of human diseases by translating information from mouse phenotypes and disease models studies to human systems. MGI provides comprehensive phenotypes for over 50,000 mutant alleles in mice and provides experimental model descriptions for over 1500 human diseases. Curated data from scientific publications are integrated with those from high-throughput phenotyping and gene expression centers. Data are standardized using defined, hierarchical vocabularies such as the Mammalian Phenotype (MP) Ontology, Mouse Developmental Anatomy and the Gene Ontologies (GO). This chapter introduces you to Gene and Allele Detail pages and provides step-by-step instructions for simple searches and those that take advantage of the breadth of MGI data integration.
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La història de les ciències en l'ensenyament de la física i la química
Traver i Ribes, Manel Josep
1996-01-01
TESI DOCTORAL : “LA HISTÒRIA DE LES CIÈNCIES EN L’ENSENYAMENT DE LA FÍSICA I LA QUÍMICA” RESUM El problema que s’ha investigat en aquest treball consisteix en l’anàlisi del paper que juga actualment la Història de la Ciència en l’ensenyament de la Física i la Química i de la seua influència en la imatge de la ciència i en les actituds dels alumnes. S’hi han investigat dues hipòtesis principals. La primera consisteix en la constatació de l’escàs paper atribuït habitualment a la His...
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MouseMine: a new data warehouse for MGI.
Motenko, H; Neuhauser, S B; O'Keefe, M; Richardson, J E
2015-08-01
MouseMine (www.mousemine.org) is a new data warehouse for accessing mouse data from Mouse Genome Informatics (MGI). Based on the InterMine software framework, MouseMine supports powerful query, reporting, and analysis capabilities, the ability to save and combine results from different queries, easy integration into larger workflows, and a comprehensive Web Services layer. Through MouseMine, users can access a significant portion of MGI data in new and useful ways. Importantly, MouseMine is also a member of a growing community of online data resources based on InterMine, including those established by other model organism databases. Adopting common interfaces and collaborating on data representation standards are critical to fostering cross-species data analysis. This paper presents a general introduction to MouseMine, presents examples of its use, and discusses the potential for further integration into the MGI interface.
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DEFF Research Database (Denmark)
Bokil, Nilesh J.; Totsika, Makrina; Carey, Alison J.
2011-01-01
assays, CFT073 was able to survive within primary mouse bone marrow-derived macrophages (BMM) up to 24h post-infection. Three additional well-characterized clinical UPEC isolates associated with distinct UTI symptomatologies displayed variable long-term survival within BMM. UPEC strains UTI89 and VR50...... or initial uptake of bacteria. E. coli UTI89 localized to a Lamp1+ vesicular compartment within BMM. In contrast to survival within mouse BMM, intracellular bacterial loads of VR50 were low in both human monocyte-derived macrophages (HMDM) and in human T24 bladder epithelial cells. Collectively, these data...
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Effect of induced peritoneal endometriosis on oocyte and embryo quality in a mouse model.
Cohen, J; Ziyyat, A; Naoura, I; Chabbert-Buffet, N; Aractingi, S; Darai, E; Lefevre, B
2015-02-01
To assess the impact of peritoneal endometriosis on oocyte and embryo quality in a mouse model. Peritoneal endometriosis was surgically induced in 33 B6CBA/F1 female mice (endometriosis group, N = 17) and sham-operated were used as control (sham group, N = 16). Mice were superovulated 4 weeks after surgery and mated or not, to collect E0.5-embryos or MII-oocytes. Evaluation of oocyte and zygote quality was done by immunofluorescence under spinning disk confocal microscopy. Endometriosis-like lesions were observed in all mice of endometriosis group. In both groups, a similar mean number of MII oocytes per mouse was observed in non-mated mice (30.2 vs 32.6), with a lower proportion of normal oocytes in the endometriosis group (61 vs 83 %, p endometriosis group (21 vs 35.5, p = 0.02) without difference in embryo quality. Our results support that induced peritoneal endometriosis in a mouse model is associated with a decrease in oocyte quality and embryo number. This experimental model allows further studies to understand mechanisms of endometriosis-associated infertility.
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Suljagić, Vesna; Jevtić, Miodrag; Djordjević, Boban; Romić, Predrag; Ilić, Radoje; Stanković, Nebojsa; Milović, Novak; Novaković, Marijan; Kozarski, Jefta; Roganović, Zoran; Popović, Zoran; Jovelić, Aleksandra
2011-08-01
Acinetobacter spp. has emerged as nosocomial pathogen during the past few decades in hospitals all over the world, but it has increasingly been implicated as a serious nosocomial pathogen in military hospitals. The aim of this study was to analyse and compare the surveillance data on Acinetobacter nosocomial colonization/infection (NCI) collected during the wartime with the data collected in peacetime. We conducted a prospective study of incidence of Acinetobacter spp. colonization/infection. Also, the two nested case-control studies were conducted. The patients with nosocomial infection (cases) were compared with those with nosocomial colonization (controls) during the two different periods, wartime and peacetime. The patients with NCI by Acinetobacter spp. were identified by the case-based surveillance. The surveillance covered all the patients in 6 surgical clinics. During the study periods a total of 166 patients had cultures that grew Acinetobacter spp. and the pooled rates of Acinetobacter spp. colonization and infection were significantly higher in wartime. When patients with NCI in wartime were compared with those with NCI in peacetime significant differences were observed. In the war year, the patients were more significantly males (p war and peace period.
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HUPO BPP pilot study: a proteomics analysis of the mouse brain of different developmental stages.
Wang, Jing; Gu, Yong; Wang, Lihong; Hang, Xingyi; Gao, Yan; Wang, Hangyan; Zhang, Chenggang
2007-11-01
This study is a part of the HUPO Brain Proteome Project (BPP) pilot study, which aims at obtaining a reliable database of mouse brain proteome, at the comparison of techniques, laboratories, and approaches as well as at preparing subsequent proteome studies of neurologic diseases. The C57/Bl6 mouse brains of three developmental stages at embryonic day 16 (E16), postnatal day 7 (P7), and 8 wk (P56) (n = 5 in each group) were provided by the HUPO BPP executive committee. The whole brain proteins of each animal were individually prepared using 2-DE coupled with PDQuest software analysis. The protein spots representing developmentally related or stably expressed proteins were then prepared with in-gel digestion followed with MALDI-TOF/TOF MS/MS and analyzed using the MASCOT search engines to search the Swiss-Prot or NCBInr database. The 2-DE gel maps of the mouse brains of all of the developmental stages were obtained and submitted to the Data Collection Centre (DCC). The proteins alpha-enolase, stathmin, actin, C14orf166 homolog, 28,000 kDa heat- and acid-stable phosphoprotein, 3-mercaptopyruvate sulfurtransferase and 40 S ribosomal protein S3a were successfully identified. A further Western blotting analysis demonstrated that enolase is a protein up-regulated in the mouse brain from embryonic stage to adult stage. These data are helpful for understanding the proteome changes in the development of the mouse brain.
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International Nuclear Information System (INIS)
Dever, Joseph T.; Elfarra, Adnan A.
2009-01-01
L-Methionine (Met) is hepatotoxic at high concentrations. Because Met toxicity in freshly isolated mouse hepatocytes is gender-dependent, the goal of this study was to assess the roles of Met accumulation and metabolism in the increased sensitivity of male hepatocytes to Met toxicity compared with female hepatocytes. Male hepatocytes incubated with Met (30 mM) at 37 o C exhibited higher levels of intracellular Met at 0.5, 1.0, and 1.5 h, respectively, compared to female hepatocytes. Conversely, female hepatocytes had higher levels of S-adenosyl-L-methionine compared to male hepatocytes. Female hepatocytes also exhibited higher L-methionine-L-sulfoxide levels relative to control hepatocytes, whereas the increases in L-methionine-D-sulfoxide (Met-D-O) levels were similar in hepatocytes of both genders. Addition of aminooxyacetic acid (AOAA), an inhibitor of Met transamination, significantly increased Met levels at 1.5 h and increased Met-D-O levels at 1.0 and 1.5 h only in Met-exposed male hepatocytes. No gender differences in cytosolic Met transamination activity by glutamine transaminase K were detected. However, female mouse liver cytosol exhibited higher methionine-DL-sulfoxide (MetO) reductase activity than male mouse liver cytosol at low (0.25 and 0.5 mM) MetO concentrations. Collectively, these results suggest that increased cellular Met accumulation, decreased Met transmethylation, and increased Met and MetO transamination in male mouse hepatocytes may be contributing to the higher sensitivity of the male mouse hepatocytes to Met toxicity in comparison with female mouse hepatocytes.
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Lee, Jung-Rok; Appelmann, Iris; Miething, Cornelius; Shultz, Tyler O; Ruderman, Daniel; Kim, Dokyoon; Mallick, Parag; Lowe, Scott W; Wang, Shan X
2018-01-01
Cancer proteomics is the manifestation of relevant biological processes in cancer development. Thus, it reflects the activities of tumor cells, host-tumor interactions, and systemic responses to cancer therapy. To understand the causal effects of tumorigenesis or therapeutic intervention, longitudinal studies are greatly needed. However, most of the conventional mouse experiments are unlikely to accommodate frequent collection of serum samples with a large enough volume for multiple protein assays towards single-object analysis. Here, we present a technique based on magneto-nanosensors to longitudinally monitor the protein profiles in individual mice of lymphoma models using a small volume of a sample for multiplex assays. Methods: Drug-sensitive and -resistant cancer cell lines were used to develop the mouse models that render different outcomes upon the drug treatment. Two groups of mice were inoculated with each cell line, and treated with either cyclophosphamide or vehicle solution. Serum samples taken longitudinally from each mouse in the groups were measured with 6-plex magneto-nanosensor cytokine assays. To find the origin of IL-6, experiments were performed using IL-6 knock-out mice. Results: The differences in serum IL-6 and GCSF levels between the drug-treated and untreated groups were revealed by the magneto-nanosensor measurement on individual mice. Using the multiplex assays and mouse models, we found that IL-6 is secreted by the host in the presence of tumor cells upon the drug treatment. Conclusion: The multiplex magneto-nanosensor assays enable longitudinal proteomic studies on mouse tumor models to understand tumor development and therapy mechanisms more precisely within a single biological object.
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9 CFR 113.33 - Mouse safety tests.
2010-01-01
... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Mouse safety tests. 113.33 Section 113.33 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Procedures § 113.33 Mouse safety tests. One of the mouse safety tests provided in this section shall be...
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NCI-60 whole exome sequencing and pharmacological CellMiner analyses.
Directory of Open Access Journals (Sweden)
William C Reinhold
Full Text Available Exome sequencing provides unprecedented insights into cancer biology and pharmacological response. Here we assess these two parameters for the NCI-60, which is among the richest genomic and pharmacological publicly available cancer cell line databases. Homozygous genetic variants that putatively affect protein function were identified in 1,199 genes (approximately 6% of all genes. Variants that are either enriched or depleted compared to non-cancerous genomes, and thus may be influential in cancer progression and differential drug response were identified for 2,546 genes. Potential gene knockouts are made available. Assessment of cell line response to 19,940 compounds, including 110 FDA-approved drugs, reveals ≈80-fold range in resistance versus sensitivity response across cell lines. 103,422 gene variants were significantly correlated with at least one compound (at p<0.0002. These include genes of known pharmacological importance such as IGF1R, BRAF, RAD52, MTOR, STAT2 and TSC2 as well as a large number of candidate genes such as NOM1, TLL2, and XDH. We introduce two new web-based CellMiner applications that enable exploration of variant-to-compound relationships for a broad range of researchers, especially those without bioinformatics support. The first tool, "Genetic variant versus drug visualization", provides a visualization of significant correlations between drug activity-gene variant combinations. Examples are given for the known vemurafenib-BRAF, and novel ifosfamide-RAD52 pairings. The second, "Genetic variant summation" allows an assessment of cumulative genetic variations for up to 150 combined genes together; and is designed to identify the variant burden for molecular pathways or functional grouping of genes. An example of its use is provided for the EGFR-ERBB2 pathway gene variant data and the identification of correlated EGFR, ERBB2, MTOR, BRAF, MEK and ERK inhibitors. The new tools are implemented as an updated web-based Cell
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The National Cancer Institute seeks parties to license human monoclonal antibodies and immunoconjugates and co-develop, evaluate, and/or commercialize large-scale antibody production and hepatocellular carcinoma (HCC) xenograft mouse models.
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Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain.
Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich
2014-01-01
The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior-posterior, dorsal-ventral and medial- lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson's disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. http://mouseidgenes.helmholtz-muenchen.de. © The Author(s) 2014. Published by Oxford University Press.
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Melozzi, Francesca; Woodman, Marmaduke M; Jirsa, Viktor K; Bernard, Christophe
2017-01-01
Connectome-based modeling of large-scale brain network dynamics enables causal in silico interrogation of the brain's structure-function relationship, necessitating the close integration of diverse neuroinformatics fields. Here we extend the open-source simulation software The Virtual Brain (TVB) to whole mouse brain network modeling based on individual diffusion magnetic resonance imaging (dMRI)-based or tracer-based detailed mouse connectomes. We provide practical examples on how to use The Virtual Mouse Brain (TVMB) to simulate brain activity, such as seizure propagation and the switching behavior of the resting state dynamics in health and disease. TVMB enables theoretically driven experimental planning and ways to test predictions in the numerous strains of mice available to study brain function in normal and pathological conditions.
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Uribe Tirado, Alejandro
2010-01-01
Objectiu. Analitzar la presència de la temàtica dels drets d'autor, dels aspectes legals de la informació acadèmica i científica, en diferents programes, cursos o programes d'aprenentatge d'alfabetització informacional (ALFIN) de diferents universitats al voltant del món, per identificar les tendències i aspectes diferenciadors que es presenten actualment respecte a la formació en aquestes temàtiques en relació amb la informació digital. També s'analitza com de preparades estan les comunitats...
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Alfano, Catherine M; Bluethmann, Shirley M; Tesauro, Gina; Perna, Frank; Agurs-Collins, Tanya; Elena, Joanne W; Ross, Sharon A; O'Connell, Mary; Bowles, Heather R; Greenberg, Deborah; Nebeling, Linda
2016-01-01
There is considerable evidence that a healthy lifestyle consisting of physical activity, healthy diet, and weight control is associated with reduced risk of morbidity and mortality after cancer. However, these behavioral interventions are not widely adopted in practice or community settings. Integrating heath behavior change interventions into standard survivorship care for the growing number of cancer survivors requires an understanding of the current state of the science and a coordinated scientific agenda for the future with focused attention in several priority areas. To facilitate this goal, this paper presents trends over the past decade of the National Cancer Institute (NCI) research portfolio, fiscal year 2004 to 2014, by funding mechanism, research focus, research design and methodology, primary study exposures and outcomes, and study team expertise and composition. These data inform a prioritized research agenda for the next decade focused on demonstrating value and feasibility and creating desire for health behavior change interventions at multiple levels including the survivor, clinician, and healthcare payer to facilitate the development and implementation of appropriately targeted, adaptive, effective, and sustainable programs for all survivors. Published by Oxford University Press (2015). This work is written by (a) US Government employee(s) and is in the public domain in the US.
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Immunostimulatory mouse granuloma protein.
Fontan, E; Fauve, R M; Hevin, B; Jusforgues, H
1983-10-01
Earlier studies have shown that from subcutaneous talc-induced granuloma in mice, a fraction could be extracted that fully protected mice against Listeria monocytogenes. Using standard biochemical procedures--i.e., ammonium sulfate fractionation, preparative electrophoresis, gel filtration chromatography, isoelectric focusing, and preparative polyacrylamide gel electrophoresis--we have now purified an active factor to homogeneity. A single band was obtained in NaDodSO4/polyacrylamide gel with an apparent Mr of 55,000. It migrated with alpha 1-globulins and the isoelectric point was 5 +/- 0.1. The biological activity was destroyed with Pronase but not with trypsin and a monospecific polyclonal rabbit antiserum was obtained. The intravenous injection of 5 micrograms of this "mouse granuloma protein" fully protects mice against a lethal inoculum of L. monocytogenes. Moreover, after their incubation with 10 nM mouse granuloma protein, mouse peritoneal cells became cytostatic against Lewis carcinoma cells.
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Directory of Open Access Journals (Sweden)
Robert C. Karn
2013-12-01
Full Text Available The overall goal of our study was to compare the proteins found in the saliva proteomes of three mammals: human, mouse and rat. Our first objective was to compare two human proteomes with very different analysis depths. The 89 shared proteins in this comparison apparently represent a core of highly-expressed human salivary proteins. Of the proteins unique to each proteome, one-half to 2/3 lack signal peptides and probably are contaminants instead of less highly-represented salivary proteins. We recently published the first rodent saliva proteomes with saliva collected from the genome mouse (C57BL/6 and the genome rat (BN/SsNHsd/Mcwi. Our second objective was to compare the proteins in the human proteome with those we identified in the genome mouse and rat to determine those common to all three mammals, as well as the specialized rodent subset. We also identified proteins unique to each of the three mammals, because differences in the secreted protein constitutions can provide clues to differences in the evolutionary adaptation of the secretions in the three different mammals.
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Mouse Resource Browser-a database of mouse databases
Zouberakis, Michael; Chandras, Christina; Swertz, Morris; Smedley, Damian; Gruenberger, Michael; Bard, Jonathan; Schughart, Klaus; Rosenthal, Nadia; Hancock, John M.; Schofield, Paul N.; Kollias, George; Aidinis, Vassilis
2010-01-01
The laboratory mouse has become the organism of choice for discovering gene function and unravelling pathogenetic mechanisms of human diseases through the application of various functional genomic approaches. The resulting deluge of data has led to the deployment of numerous online resources and the
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MS_HistoneDB, a manually curated resource for proteomic analysis of human and mouse histones.
El Kennani, Sara; Adrait, Annie; Shaytan, Alexey K; Khochbin, Saadi; Bruley, Christophe; Panchenko, Anna R; Landsman, David; Pflieger, Delphine; Govin, Jérôme
2017-01-01
Histones and histone variants are essential components of the nuclear chromatin. While mass spectrometry has opened a large window to their characterization and functional studies, their identification from proteomic data remains challenging. Indeed, the current interpretation of mass spectrometry data relies on public databases which are either not exhaustive (Swiss-Prot) or contain many redundant entries (UniProtKB or NCBI). Currently, no protein database is ideally suited for the analysis of histones and the complex array of mammalian histone variants. We propose two proteomics-oriented manually curated databases for mouse and human histone variants. We manually curated >1700 gene, transcript and protein entries to produce a non-redundant list of 83 mouse and 85 human histones. These entries were annotated in accordance with the current nomenclature and unified with the "HistoneDB2.0 with Variants" database. This resource is provided in a format that can be directly read by programs used for mass spectrometry data interpretation. In addition, it was used to interpret mass spectrometry data acquired on histones extracted from mouse testis. Several histone variants, which had so far only been inferred by homology or detected at the RNA level, were detected by mass spectrometry, confirming the existence of their protein form. Mouse and human histone entries were collected from different databases and subsequently curated to produce a non-redundant protein-centric resource, MS_HistoneDB. It is dedicated to the proteomic study of histones in mouse and human and will hopefully facilitate the identification and functional study of histone variants.
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Tendències de les publicacions informatives cientificomèdiques en l'era 2.0
Directory of Open Access Journals (Sweden)
González Pacanowski, Antonio
2014-12-01
Full Text Available En els últims anys ha crescut l'audiència que consulta continguts de salut en publicacions i mitjans a Internet, especialment a Europa i als Estats Units. S'ha passat d'un usuari d'Internet unidireccional en la comunicació a un escenari en el qual la multidireccionalitat i la instantaneïtat són constants. Els nous mitjans i la creació de plataformes d'intercanvi d'informació més especialitzada mostren que els recursos multimèdia i la interactivitat també poden donar-se en mitjans especialitzats i distants del públic general com ara informació sobre biomedicina i salut. Simultàniament, el canvi cap a actituds més solidàries i d'ajuda mútua aflora mitjançant les xarxes socials. Amb l'objectiu de traçar un escenari sobre el comportament de les audiències davant els continguts de caràcter científic, especialment els de tipus sanitari, s'analitzen en aquest treball els perfils i costums dels usuaris utilitzant referències estadístiques tant europees com nord-americanes. De la mateixa manera, s'identifica el mapa actual de cibermitjans relacionats amb la informació cientificomèdica segmentada en mitjans de comunicació generals, especialitzats i els propis del web 2.0, com ara blogs i mitjans cocreatius. Aquesta descripció permet orientar sobre les tendències que seguiran els públics diferents i segmentats, però ara interconnectats per les noves tecnologies, i sobre la transformació de l'arquitectura i les funcionalitats dels mitjans a Internet.En los últimos años ha crecido la audiencia que consulta contenidos de salud en publicaciones y medios en Internet, especialmente en Europa y Estados Unidos. Se ha pasado de un usuario de Internet unidireccional en la comunicación a un escenario en el que la multidireccionalidad y la instantaneidad son constantes. Los nuevos medios y la creación de plataformas de intercambio de información más especializada evidencian que los recursos multimedia y la interactividad tambi
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EuroPhenome and EMPReSS: online mouse phenotyping resource.
Mallon, Ann-Marie; Blake, Andrew; Hancock, John M
2008-01-01
EuroPhenome (http://www.europhenome.org) and EMPReSS (http://empress.har.mrc.ac.uk/) form an integrated resource to provide access to data and procedures for mouse phenotyping. EMPReSS describes 96 Standard Operating Procedures for mouse phenotyping. EuroPhenome contains data resulting from carrying out EMPReSS protocols on four inbred laboratory mouse strains. As well as web interfaces, both resources support web services to enable integration with other mouse phenotyping and functional genetics resources, and are committed to initiatives to improve integration of mouse phenotype databases. EuroPhenome will be the repository for a recently initiated effort to carry out large-scale phenotyping on a large number of knockout mouse lines (EUMODIC).
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Chu, Tai-Lin; Abdul Aziz, Norazlin; Mohd Kornain, Noor-Kaslina; Samiulla, D. S.; Lo, Kwok-Wai; Ng, Chew-Hee
2018-01-01
Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity. PMID:29329342
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Shin, Na-Rae; Ryu, Hyung-Won; Ko, Je-Won; Park, Ji-Won; Kwon, Ok-Kyoung; Oh, Sei-Ryang; Kim, Jong-Choon; Shin, In-Sik; Ahn, Kyung-Seop
2016-12-24
A standardized bark extract of Pinus pinaster Aiton (Pycnogenol ® ; PYC) used as an herbal medicine to treat various diseases in Europe and North America. This study evaluates the ability of PYC to inhibit chronic obstructive pulmonary disease (COPD) in the cigarette smoke extract (CSE)-stimulated human airway epithelial cell line NCI-H292 and in a cigarette smoke (CS) and lipopolysaccharide (LPS)-induced mouse model. To induce COPD, the mice intranasally received LPS on day 4 and were exposed to CS for 1h per day (total eight cigarettes per day) from days 1-7. The mice were administered PYC at a dose of 15mg/kg and 30mg/kg 1h before CS exposure. In the CSE-stimulated NCI-H292 cells, PYC significantly inhibited Erk phosphorylation, sp1 expression, MUC5AC, and pro-inflammatory cytokines in a concentration-dependent manner, as evidenced by a reduction in their mRNA levels. Co-treatment with PYC and Erk inhibitors markedly reduced the levels inflammatory mediators compared to only PYC-treatment. In the COPD mice model, PYC decreased the inflammatory cell count and the levels of pro-inflammatory cytokines in the broncho-alveolar lavage fluid compared with COPD mice. PYC attenuated the recruitment of inflammatory cells in the airways and decreased the expression levels of Erk phosphorylation and sp1. PYC also inhibited the expression of myeloperoxidase and matrix metalloproteinases-9 in lung tissue. Our results indicate that PYC inhibited the reduction in the inflammatory response in CSE-stimulated NCI-H292 cells and the COPD mouse model via the Erk-sp1 pathway. Therefore, we suggest that PYC has the potential to treat COPD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
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Teratology studies in the mouse.
Marsden, Edward; Leroy, Mariline
2013-01-01
The rat is the routine species of choice as the rodent model for regulatory safety testing of xenobiotics such as medicinal products, food additives, and other chemicals. However, the rat is not always suitable for pharmacological, toxicological, immunogenic, pharmacokinetic, or even practical reasons. Under such circumstances, the mouse offers an alternative for finding a suitable rodent model acceptable to the regulatory authorities. Since all essential routes of administration are possible, the short reproductive cycle and large litter size of the mouse make it a species well adapted for use in teratology studies. Given that good quality animals, including virgin mated females, can be acquired relatively easily and inexpensively, the mouse has been used in reproductive toxicity studies for decades and study protocols are well established.
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DEFF Research Database (Denmark)
Lagkouvardos, Ilias; Pukall, Rüdiger; Abt, Birte
2016-01-01
species are specific to the mouse intestine and that a minimal consortium of 18 strains covered 50-75% of the known functional potential of metagenomes. The present work will sustain future research on microbiota-host interactions in health and disease, as it will facilitate targeted colonization...
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Hyperelastic Material Properties of Mouse Skin under Compression.
Directory of Open Access Journals (Sweden)
Yuxiang Wang
Full Text Available The skin is a dynamic organ whose complex material properties are capable of withstanding continuous mechanical stress while accommodating insults and organism growth. Moreover, synchronized hair cycles, comprising waves of hair growth, regression and rest, are accompanied by dramatic fluctuations in skin thickness in mice. Whether such structural changes alter skin mechanics is unknown. Mouse models are extensively used to study skin biology and pathophysiology, including aging, UV-induced skin damage and somatosensory signaling. As the skin serves a pivotal role in the transfer function from sensory stimuli to neuronal signaling, we sought to define the mechanical properties of mouse skin over a range of normal physiological states. Skin thickness, stiffness and modulus were quantitatively surveyed in adult, female mice (Mus musculus. These measures were analyzed under uniaxial compression, which is relevant for touch reception and compression injuries, rather than tension, which is typically used to analyze skin mechanics. Compression tests were performed with 105 full-thickness, freshly isolated specimens from the hairy skin of the hind limb. Physiological variables included body weight, hair-cycle stage, maturity level, skin site and individual animal differences. Skin thickness and stiffness were dominated by hair-cycle stage at young (6-10 weeks and intermediate (13-19 weeks adult ages but by body weight in mature mice (26-34 weeks. Interestingly, stiffness varied inversely with thickness so that hyperelastic modulus was consistent across hair-cycle stages and body weights. By contrast, the mechanics of hairy skin differs markedly with anatomical location. In particular, skin containing fascial structures such as nerves and blood vessels showed significantly greater modulus than adjacent sites. Collectively, this systematic survey indicates that, although its structure changes dramatically throughout adult life, mouse skin at a given
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Circadian oscillators in the mouse brain
DEFF Research Database (Denmark)
Rath, Martin F; Rovsing, Louise; Møller, Morten
2014-01-01
with conditional cell-specific clock gene deletions. This prompted us to analyze the molecular clockwork of the mouse neocortex and cerebellum in detail. Here, by use of in situ hybridization and quantitative RT-PCR, we show that clock genes are expressed in all six layers of the neocortex and the Purkinje...... and granular cell layers of the cerebellar cortex of the mouse brain. Among these, Per1, Per2, Cry1, Arntl, and Nr1d1 exhibit circadian rhythms suggesting that local running circadian oscillators reside within neurons of the mouse neocortex and cerebellar cortex. The temporal expression profiles of clock genes...... are similar in the neocortex and cerebellum, but they are delayed by 5 h as compared to the SCN, suggestively reflecting a master-slave relationship between the SCN and extra-hypothalamic oscillators. Furthermore, ARNTL protein products are detectable in neurons of the mouse neocortex and cerebellum...
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McKinley, Eliot T; Bugaj, Joseph E; Zhao, Ping; Guleryuz, Saffet; Mantis, Christine; Gokhale, Prafulla C; Wild, Robert; Manning, H Charles
2011-05-15
To evaluate 2-deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography imaging ((18)FDG-PET) as a predictive, noninvasive, pharmacodynamic (PD) biomarker of response following administration of a small-molecule insulin-like growth factor-1 receptor and insulin receptor (IGF-1R/IR) inhibitor, OSI-906. In vitro uptake studies of (3)H-2-deoxy glucose following OSI-906 exposure were conducted evaluating correlation of dose with inhibition of IGF-1R/IR as well as markers of downstream pathways and glucose metabolism. Similarly, in vivo PD effects were evaluated in human tumor cell line xenografts propagated in athymic nude mice by (18)FDG-PET at 2, 4, and 24 hours following a single treatment of OSI-906 for the correlation of inhibition of receptor targets and downstream markers. Uptake of (3)H-2-deoxy glucose and (18)FDG was significantly diminished following OSI-906 exposure in sensitive tumor cells and subcutaneous xenografts (NCI-H292) but not in an insensitive model lacking IGF-1R expression (NCI-H441). Diminished PD (18)FDG-PET, collected immediately following the initial treatment agreed with inhibition of pIGF-1R/pIR, reduced PI3K (phosphoinositide 3-kinase) and MAPK (mitogen activated protein kinase) pathway activity, and predicted tumor growth arrest as measured by high-resolution ultrasound imaging. (18)FDG-PET seems to serve as a rapid, noninvasive PD marker of IGF-1R/IR inhibition following a single dose of OSI-906 and should be explored clinically as a predictive clinical biomarker in patients undergoing IGF-1R/IR-directed cancer therapy. ©2011 AACR.
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Groner, B; Hynes, N E
1980-01-01
The Southern DNA filter transfer technique was used to characterize the genomic location of the mouse mammary tumor proviral DNA in different inbred strains of mice. Two of the strains (C3H and CBA) arose from a cross of a Bagg albino (BALB/c) mouse and a DBA mouse. The mouse mammary tumor virus-containing restriction enzyme DNA fragments of these strains had similar patterns, suggesting that the proviruses of these mice are in similar genomic locations. Conversely, the pattern arising from the DNA of the GR mouse, a strain genetically unrelated to the others, appeared different, suggesting that its mouse mammary tumor proviruses are located in different genomic sites. The structure of another gene, that coding for beta-globin, was also compared. The mice strains which we studied can be categorized into two classes, expressing either one or two beta-globin proteins. The macroenvironment of the beta-globin gene appeared similar among the mice strains belonging to one genetic class. Female mice of the C3H strain exogenously transmit mouse mammary tumor virus via the milk, and their offspring have a high incidence of mammary tumor occurrence. DNA isolated from individual mammary tumors taken from C3H mice or from BALB/c mice foster nursed on C3H mothers was analyzed by the DNA filter transfer technique. Additional mouse mammary tumor virus-containing fragments were found in the DNA isolated from each mammary tumor. These proviral sequences were integrated into different genomic sites in each tumor. Images PMID:6245257
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Optimization of a protocol for cryopreservation of mouse spermatozoa using cryotubes.
Hasegawa, Ayumi; Yonezawa, Kazuya; Ohta, Akihiko; Mochida, Keiji; Ogura, Atsuo
2012-01-01
The rapid increase in the number of genetically modified mouse strains has produced a high demand for their frozen spermatozoa from laboratories and mouse banking facilities. Historically, plastic straws have been used preferentially as containers for frozen mammalian spermatozoa because spermatozoa frozen in plastic straws have a high survival rate after thawing. However, plastic straws are more fragile and are used less often than the cryotubes used for conventional cell freezing. In this study, we sought to develop a new protocol for sperm freezing using cryotubes as the container to increase the accessibility of mouse sperm cryopreservation. Epididymal spermatozoa were collected from mature ICR or C57BL/6J (B6) males and were suspended in 18% raffinose and 3% skim milk solution. We then optimized the following conditions using the sperm survival rate as an index: 1) distance of cryotubes from the surface of the liquid nitrogen at freezing, 2) volume of the sperm suspension in the cryotube and 3) temperature of warming sperm during thawing. The best result was obtained when cryotubes containing 10 µl of sperm suspension were immersed 1 cm below the surface of the liquid nitrogen and then thawed at 50 C. The fertilization rates using spermatozoa frozen and thawed using this method were 63.1% in ICR mice and 28.2% in B6 mice. The latter rate was increased to 62.3% by adding reduced glutathione to the fertilization medium. After embryo transfer, 68% and 62% of the fertilized oocytes developed into normal offspring in the ICR and B6 strains, respectively. These results show that cryotubes can be used for cryopreservation of mouse spermatozoa under optimized conditions. This protocol is easy and reproducible, and it may be used in laboratories that do not specialize in sperm cryopreservation.
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Directory of Open Access Journals (Sweden)
Nicolas Torquet
2016-09-01
Full Text Available Ultrasonic vocalisation is a broadly used proxy to evaluate social communication in mouse models of neuropsychiatric disorders. The efficacy and robustness of testing these models suffer from limited knowledge of the structure and functions of these vocalisations as well as of the way to analyse the data. We created mouseTube, an open database with a web interface, to facilitate sharing and comparison of ultrasonic vocalisations data and metadata attached to a recording file. Metadata describe 1 the acquisition procedure, e.g., hardware, software, sampling frequency, bit depth; 2 the biological protocol used to elicit ultrasonic vocalisations; 3 the characteristics of the individual emitting ultrasonic vocalisations (e.g., strain, sex, age. To promote open science and enable reproducibility, data are made freely available. The website provides searching functions to facilitate the retrieval of recording files of interest. It is designed to enable comparisons of ultrasonic vocalisation emission between strains, protocols or laboratories, as well as to test different analysis algorithms and to search for protocols established to elicit mouse ultrasonic vocalisations. Over the long term, users will be able to download and compare different analysis results for each data file. Such application will boost the knowledge on mouse ultrasonic communication and stimulate sharing and comparison of automatic analysis methods to refine phenotyping techniques in mouse models of neuropsychiatric disorders.
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77 FR 59624 - Submission for OMB Review; Comment Request; CareerTrac
2012-09-28
... collection system provides a streamlined, web-based application permitting Principal Investigators to record... (NIGMS), National Cancer Institute (NCI), and National Library of Medicine (NLM) of the National....: 0925-0568). Need and Use of Information Collection: This data collection system is being developed to...
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Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis
Chen, Hung-Chih; Chin, Yu-Feng; Lundy, David J.; Liang, Chung-Tiang; Chi, Ya-Hui; Kuo, Paolin; Hsieh, Patrick C. H.
2017-01-01
Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder resulting from mutations in the dystrophin gene. The mdx/utrn ?/? mouse, lacking in both dystrophin and its autosomal homologue utrophin, is commonly used to model the clinical symptoms of DMD. Interestingly, these mice are infertile but the mechanisms underlying this phenomenon remain unclear. Using dystrophin deficient mdx mouse and utrophin haplodeficient mdx/utrn +/? mouse models, we demonstrate the contribution of Dp427 (f...
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Mousetrap: An integrated, open-source mouse-tracking package.
Kieslich, Pascal J; Henninger, Felix
2017-10-01
Mouse-tracking - the analysis of mouse movements in computerized experiments - is becoming increasingly popular in the cognitive sciences. Mouse movements are taken as an indicator of commitment to or conflict between choice options during the decision process. Using mouse-tracking, researchers have gained insight into the temporal development of cognitive processes across a growing number of psychological domains. In the current article, we present software that offers easy and convenient means of recording and analyzing mouse movements in computerized laboratory experiments. In particular, we introduce and demonstrate the mousetrap plugin that adds mouse-tracking to OpenSesame, a popular general-purpose graphical experiment builder. By integrating with this existing experimental software, mousetrap allows for the creation of mouse-tracking studies through a graphical interface, without requiring programming skills. Thus, researchers can benefit from the core features of a validated software package and the many extensions available for it (e.g., the integration with auxiliary hardware such as eye-tracking, or the support of interactive experiments). In addition, the recorded data can be imported directly into the statistical programming language R using the mousetrap package, which greatly facilitates analysis. Mousetrap is cross-platform, open-source and available free of charge from https://github.com/pascalkieslich/mousetrap-os .
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2010-05-07
... target audiences. Additionally, since OAR is responsible for matching advocates to NCI programs and... characteristics (attitudes, beliefs, and behaviors) of the intended target audience and use this information in..., appropriateness, and impact for/ to target audiences; and (3) expend limited program resource dollars wisely and...
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Directory of Open Access Journals (Sweden)
Yuan CX
2015-03-01
Full Text Available Chun-Xiu Yuan,1,2 Zhi-Wei Zhou,2,3 Yin-Xue Yang,4 Zhi-Xu He,3 Xueji Zhang,5 Dong Wang,6 Tianxing Yang,7 Si-Yuan Pan,8 Xiao-Wu Chen,9 Shu-Feng Zhou2 1Department of Oncology, General Hospital, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, 4Department of Colorectal Surgery, General Hospital, Ningxia Medical University, Yinchuan, 5Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, 6Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People’s Republic of China; 7Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USA; 8Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 9Department of General Surgery, The First People’s Hospital of Shunde, Southern Medical University, Shunde, People’s Republic of China Abstract: Gastric cancer is the second leading cause of cancer-related death worldwide, with a poor response to current chemotherapy. Danusertib is a pan-inhibitor of the Aurora kinases and a third-generation Bcr-Abl tyrosine kinase inhibitor with potent anticancer effects, but its antitumor effect and underlying mechanisms in the treatment of human gastric cancer are unknown. This study aimed to investigate the effects of danusertib on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition and the molecular mechanisms involved in human gastric cancer AGS and NCI-N78 cells. The results showed that danusertib had potent growth-inhibitory, apoptosis-inducing, and
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Melatonin receptors: latest insights from mouse models
Tosini, Gianluca; Owino, Sharon; Guillame, Jean-Luc; Jockers, Ralf
2014-01-01
Summary Melatonin, the neuro-hormone synthesized during the night, has recently seen an unexpected extension of its functional implications towards type 2 diabetes development, visual functions, sleep disturbances and depression. Transgenic mouse models were instrumental for the establishment of the link between melatonin and these major human diseases. Most of the actions of melatonin are mediated by two types of G protein-coupled receptors, named MT1 and MT2, which are expressed in many different organs and tissues. Understanding the pharmacology and function of mouse MT1 and MT2 receptors, including MT1/MT2 heteromers, will be of crucial importance to evaluate the relevance of these mouse models for future therapeutic developments. This review will critically discuss these aspects, and give some perspectives including the generation of new mouse models. PMID:24903552
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Nkungli, Nyiang Kennet; Ghogomu, Julius Numbonui
2017-07-01
Thiosemicarbazones display diverse pharmacological properties, including antimalarial activities. Their pharmacological activities have been studied in depth, but little of this research has focused on their antimalarial mode of action. To elucidate this antimalarial mechanism, we investigated the nature of the interactions between iron(III) protoporphyrin IX (Fe(III)PPIX) and the thione-thiol tautomers of 4-methoxyacetophenone thiosemicarbazone (MAPTSC). Dispersion-corrected density functional theory (DFT-D3), the quantum theory of atoms in molecules (QTAIM), the noncovalent interaction (NCI) index, the electron localization function (ELF), the localized orbital locator (LOL), and thermodynamic calculations were employed in this work. Fe(III)PPIX-MAPTSC binding is expected to inhibit hemozoin formation, thereby preventing Fe(III)PPIX detoxification in plasmodia. Preliminary studies geared toward the identification of atomic binding sites in the thione-thiol tautomers of MAPTSC were carried out using molecular electrostatic potential (MEP) maps and conceptual DFT-based local reactivity indices. The thionic sulfur and the 2 N-azomethine nitrogen/thiol sulfur of, respectively, the thione and thiol tautomers of MAPTSC were identified as the most favorable nucleophilic sites for electrophilic attack. The negative values of the computed Fe(III)PPIX-MAPTSC binding energies, enthalpies, and Gibbs free energies are indicative of the existence and stability of Fe(III)PPIX-MAPTSC complexes. MAPTSC-Fe(III) coordinate bonds and strong hydrogen bonds (N-H···O) between the NH 2 group in MAPTSC and the C=O group in one propionate side chain of Fe(III)PPIX are crucial to Fe(III)PPIX-MAPTSC binding. QTAIM, NCI, ELF, and LOL analyses revealed a subtle interplay of weak noncovalent interactions dominated by dispersive-like van der Waals interactions between Fe(III)PPIX and MAPTSC that stabilize the Fe(III)PPIX-MAPTSC complexes.
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International Nuclear Information System (INIS)
Seino, Noritaka
1995-01-01
To investigate the radioprotective effect of dipyridamole in the aging mouse, the lipid peroxide content in aging mouse liver, spleen and brain irradiated by X-ray were measured both before and after injection of dipyridamole. The lipid peroxide content increased with aging from 2 months old to 16 months old in the mouse liver, spleen and brain. The content of lipid peroxide in the liver and spleen of the aging mouse was significantly increased in 7 days after whole-body irradiation with 8 Gy, but was unchanged in the brain. Dipyridamole, given before irradiation, significantly inhibited the increase of lipid peroxide after irradiation. These results suggest that dipyridamole may have radioprotective effects on aging mouse liver and spleen as well as on young mouse, and that inhibition of lipid peroxidation is a possible factor in the radioprotective effect of dipyridamole. (author)
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He, Xuzhi; Cruz, Jazmina L; Joseph, Shannon; Pett, Nicola; Chew, Hui Yi; Tuong, Zewen K; Okano, Satomi; Kelly, Gabrielle; Veitch, Margaret; Simpson, Fiona; Wells, James W
2018-02-23
The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer. However, only 15-20% patients benefit from this drug, thus new strategies to improve cetuximab efficiency are required. We aimed to develop a reliable and easy preclinical mouse model to evaluate the efficacy of EGFR-targeted antibodies and examine the immune mechanisms involved in tumour regression. We selected an anti-mouse EGFR mAb, 7A7, which has been reported to be "mouse cetuximab" and to exhibit similar properties to its human counterpart. Unfortunately, we were unable to reproduce previous results obtained with the 7A7 mAb. In our hands, 7A7 failed to recognize mouse EGFR, both in native and reducing conditions. Moreover, in vivo administration of 7A7 in an EGFR-expressing HPV38 tumour model did not have any impact on tumour regression or animal survival. We conclude that 7A7 does not recognize mouse EGFR and therefore cannot be used as the mouse equivalent of cetuximab use in humans. As a number of groups have spent effort and resources with similar issues we feel that publication is a responsible approach.
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An atlas of the prenatal mouse brain: gestational day 14.
Schambra, U B; Silver, J; Lauder, J M
1991-11-01
A prenatal atlas of the mouse brain is presently unavailable and is needed for studies of normal and abnormal development, using techniques including immunocytochemistry and in situ hybridization. This atlas will be especially useful for researchers studying transgenic and mutant mice. This collection of photomicrographs and corresponding drawings of Gestational Day (GD) 14 mouse brain sections is an excerpt from a larger atlas encompassing GD 12-18. In composing this atlas, available published studies on the developing rodent brain were consulted to aid in the detailed labeling of embryonic brain structures. C57Bl/6J mice were mated for 1 h, and the presence of a copulation plug was designated as GD 0. GD 14 embryos were perfused transcardially with 4% paraformaldehyde in 0.1 M phosphate buffer and embedded in paraffin. Serial sections (10 microns thickness) were cut through whole heads in sagittal and horizontal planes. They were stained with hematoxylin and eosin and photographed. Magnifications were 43X and 31X for the horizontal and sagittal sections, respectively. Photographs were traced and line drawings prepared using an Adobe Illustrator on a Macintosh computer.
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A report from the Sixth International Mouse Genome Conference
Energy Technology Data Exchange (ETDEWEB)
Brown, S. [Saint Mary`s Hospital Medical School, London (United Kingdom). Dept. of Biochemistry and Molecular Genetics
1992-12-31
The Sixth Annual Mouse Genome Conference was held in October, 1992 at Buffalo, USA. The mouse is one of the primary model organisms in the Human Genome Project. Through the use of gene targeting studies the mouse has become a powerful biological model for the study of gene function and, in addition, the comparison of the many homologous mutations identified in human and mouse have widened our understanding of the biology of these two organisms. A primary goal in the mouse genome program has been to create a genetic map of STSs of high resolution (<1cM) that would form the basis for the physical mapping of the whole mouse genome. Buffalo saw substantial new progress towards the goal of a very high density genetic map and the beginnings of substantive efforts towards physical mapping in chromosome regions with a high density of genetic markers.
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DEFF Research Database (Denmark)
Schneider, H R; Reichert, G H; Issinger, O G
1986-01-01
Mouse embryos at various stages of development were used to study the relationship of protein kinase activities with normal embryogenesis. Casein kinase II (CKII) activity in developing mouse embryos shows a 3-4-fold activity increase at day 12 of gestation. Together with the CKII activity...... mouse tumour cells also show an enhanced CKII activity. Here too, a 110-kDa phosphoprotein was the major phosphoryl acceptor. Partial proteolytic digestion shows that both proteins are identical. Other protein kinases tested (cAMP- and cGMP-dependent protein kinases) only show a basal level of enzyme...
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The MAGIC Touch: Combining MAGIC-Pointing with a Touch-Sensitive Mouse
Drewes, Heiko; Schmidt, Albrecht
In this paper, we show how to use the combination of eye-gaze and a touch-sensitive mouse to ease pointing tasks in graphical user interfaces. A touch of the mouse positions the mouse pointer at the current gaze position of the user. Thus, the pointer is always at the position where the user expects it on the screen. This approach changes the user experience in tasks that include frequent switching between keyboard and mouse input (e.g. working with spreadsheets). In a user study, we compared the touch-sensitive mouse with a traditional mouse and observed speed improvements for pointing tasks on complex backgrounds. For pointing task on plain backgrounds, performances with both devices were similar, but users perceived the gaze-sensitive interaction of the touch-sensitive mouse as being faster and more convenient. Our results show that using a touch-sensitive mouse that positions the pointer on the user’s gaze position reduces the need for mouse movements in pointing tasks enormously.
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DEFF Research Database (Denmark)
André, Viola; Gau, Christine; Scheideler, Angelika
2018-01-01
Animal welfare requires the adequate housing of animals to ensure health and well-being. The application of environmental enrichment is a way to improve the well-being of laboratory animals. However, it is important to know whether these enrichment items can be incorporated in experimental mouse...... material and shelters may be used to improve animal welfare without impairment of experimental outcome or loss of comparability to previous data collected under barren housing conditions....
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DEFF Research Database (Denmark)
Lukácová, Slávka; Khalil, Azza Ahmed; Overgaard, Jens
2005-01-01
To investigate the possible relationship between radiobiological hypoxia in a C3H mouse mammary carcinoma and osteopontin (OPN) levels measured in mouse serum. MATERIAL AND METHODS: Experiments were performed in CDF1 mice that were either non-tumour bearing or with different sized tumours implanted...... in the right rear foot. Osteopontin levels in extracted mouse blood serum and tissue from the transplanted tumours were measured using an ELISA assay. The tumour oxygenation status was estimated using the Eppendorf Histograph and the fraction of oxygen partial pressure (pO2) values =5 mm Hg (HF5...
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2011-08-02
.... Formative research in the area of theory development and validation would provide the basis for developing...) Develop and refine integrative theories; (3) Identify and observe theoretical and innovative trends in... Request; A Generic Submission for Theory Development and Validation (NCI) SUMMARY: Under the provisions of...
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Sequence and chromosomal localization of the mouse brevican gene
DEFF Research Database (Denmark)
Rauch, U; Meyer, H; Brakebusch, C
1997-01-01
Brevican is a brain-specific proteoglycan belonging to the aggrecan family. Phage clones containing the complete mouse brevican open reading frame of 2649 bp and the complete 3'-untranslated region of 341 bp were isolated from a mouse brain cDNA library, and cosmid clones containing the mouse...
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The wobbler mouse, an ALS animal model
DEFF Research Database (Denmark)
Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas
2013-01-01
This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...
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Smc1β is required for activation of SAC during mouse oocyte meiosis.
Miao, Yilong; Zhou, Changyin; Cui, Zhaokang; Dai, Xiaoxin; Zhang, Mianqun; Lu, Yajuan; Xiong, Bo
2017-03-19
Smc1β is a meiosis-specific cohesin subunit that is essential for sister chromatid cohesion and DNA recombination. Previous studies have shown that Smc1β-deficient mice in both sexes are sterile. Ablation of Smc1β during male meiosis leads to the blockage of spermatogenesis in pachytene stage, and ablation of Smc1β during female meiosis generates a highly error-prone oocyte although it could develop to metaphase II stage. However, the underlying mechanisms regarding how Smc1β maintains the correct meiotic progression in mouse oocytes have not been clearly defined. Here, we find that GFP-fused Smc1β is expressed and localized to the chromosomes from GV to MII stages during mouse oocyte meiotic maturation. Knockdown of Smc1β by microinjection of gene-specific morpholino causes the impaired spindle apparatus and chromosome alignment which are highly correlated with the defective kinetochore-microtubule attachments, consequently resulting in a prominently higher incidence of aneuploid eggs. In addition, the premature extrusion of polar bodies and escape of metaphase I arrest induced by low dose of nocodazole treatment in Smc1β-depleted oocytes indicates that Smc1β is essential for activation of spindle assembly checkpoint (SAC) activity. Collectively, we identify a novel function of Smc1β as a SAC participant beyond its role in chromosome cohesion during mouse oocyte meiosis.
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Chemical Aspects of Lesser Mouse Deer Meat
Directory of Open Access Journals (Sweden)
Djalal Rosyidi
2012-02-01
Full Text Available An experiment aiming for studying chemical aspects of lesser mouse deer meat (Tragulus javanicus. This research explored the chemical aspects of lesser mouse deer meat (Tragulus javanicus. Eight lesser mouse deer (four female and four male were used in chemical aspects of lesser mouse deer meat. The parameters observed included proximate analysis, amino acid, fatty acid, cholesterol and EPA-DHA of the meat. The results showed that average meat chemical composition were content of water, protein, fat, ash and cholesterol were 76.33 %, 21.42 %, 0.51 %, 1.20% and 50.00 mg/100 g, respectively. Fatty acid consist of lauric acid, miristate, palmitate, stearic, oleic, linoleic, and linolenic were 1.04 % 3.09%, 30.97, 0.77%., 59.41%, 3.22% and 1.12%, respectively. The total EPA and DHA was 0.13% and 0.05%, Keywords: amino acid, fatty acid, cholesterol and EPA-DHA
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A catalog of the mouse gut metagenome
DEFF Research Database (Denmark)
Xiao, Liang; Feng, Qiang; Liang, Suisha
2015-01-01
laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human......We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing...... counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies....
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Lu, Xing; Wu, Yi-Ming; Yang, Jing-Mei; Ma, Feng-E; Li, Liang-Ping; Chen, Sheng; Zhang, Ye; Ni, Qing-Ling; Pan, Ying-Ming; Hong, Xue; Peng, Yan
2018-05-10
A series of 2(1H)-quinolinone derivatives and their rhodium (III) complexes were designed and synthesized. All the rhodium (III) complexes exhibited higher in vitro cytotoxicity for Hep G2, HeLa 229, MGC80-3, and NCI-H460 human tumor cell lines than their ligands and cisplatin, and among them complex 9 was found to be selectively cytotoxic to tumor cells. Further investigation revealed that complex 9 caused cell cycle arrest at the G2/M phase and induced apoptosis, and inhibited the proliferation of Hep G2 cells by impeding the phosphorylation of epidermal growth factor receptor (EGFR) and its downstream enzymes. Complex 9 also up-regulated the proapoptotic proteins Bak, Bax, and Bim, which altogether activated caspase-3/9 to initiate cell apoptosis. Notably, complex 9 effectively inhibited tumor growth in the NCI-H460 xenograft mouse model with less adverse effect than cisplatin. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
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STIM1fl/fl Ksp-Cre Mouse has Impaired Renal Water Balance
Directory of Open Access Journals (Sweden)
Liudmila Cebotaru
2016-06-01
Full Text Available Background/AIM: STIM1 is as an essential component in store operated Ca2+ entry. However give the paucity of information on the role of STIM1 in kidney, the aim was to study the function of STIM1 in the medulla of the kidney. Methods: we crossed a Ksp-cre mouse with another mouse containing two loxP sites flanking Exon 6 of STIM1. The Ksp-cre mouse is based upon the Ksp-cadherin gene promoter which expresses cre recombinase in developing nephrons, collecting ducts (SD and thick ascending limbs (TAL of the loop of Henle. Results: The offspring of these mice are viable without gross morphological changes, however, we noticed that the STIM1 Ksp-cre knockout mice produced more urine compared to control. To examine this more carefully, we fed mice low (LP and high protein (HP diets respectively. When mice were fed HP diet STIM1 ko mice had significantly increased urinary volume and lower specific gravity compared to wt mice. In STIM1 ko mice fed HP diet urine creatinine and urea were significantly lower compared to wt mice fed HP diet, however the fractional excretion was the same. Conclusion: These data support the idea that STIM1 ko mice have impaired urinary concentrating ability when challenged with HP diet is most likely caused by impaired Ca2+-dependent signal transduction through the vasopressin receptor cascade.
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Czech Academy of Sciences Publication Activity Database
Pelantová, Helena; Bugáňová, Martina; Anýž, J.; Železná, Blanka; Maletínská, Lenka; Novák, D.; Haluzík, M.; Kuzma, Marek
2015-01-01
Roč. 115, NOV 10 (2015), s. 225-235 ISSN 0731-7085 R&D Projects: GA ČR GA13-14105S; GA MŠk LO1509 Grant - others:OPPC(XE) CZ.2.16/3.1.00/24023 Institutional support: RVO:61388971 ; RVO:61388963 Keywords : NMR metabolomics * Mouse * Obesity Subject RIV: CB - Analytical Chemistry, Separation; CB - Analytical Chemistry, Separation (UOCHB-X) OBOR OECD: Analytical chemistry; Analytical chemistry (UOCHB-X) Impact factor: 3.169, year: 2015
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10. international mouse genome conference
Energy Technology Data Exchange (ETDEWEB)
Meisler, M.H.
1996-12-31
Ten years after hosting the First International Mammalian Genome Conference in Paris in 1986, Dr. Jean-Louis Guenet presided over the Tenth Conference at the Pasteur Institute, October 7--10, 1996. The 1986 conference was a satellite to the Human Gene Mapping Workshop and had approximately 50 attendees. The 1996 meeting was attended by 300 scientists from around the world. In the interim, the number of mapped loci in the mouse increased from 1,000 to over 20,000. This report contains a listing of the program and its participants, and two articles that review the meeting and the role of the laboratory mouse in the Human Genome project. More than 200 papers were presented at the conference covering the following topics: International mouse chromosome committee meetings; Mutant generation and identification; Physical and genetic maps; New technology and resources; Chromatin structure and gene regulation; Rate and hamster genetic maps; Informatics and databases; and Quantitative trait analysis.
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Mouse Models of Gastric Cancer
Hayakawa, Yoku; Fox, James G.; Gonda, Tamas; Worthley, Daniel L.; Muthupalani, Sureshkumar; Wang, Timothy C.
2013-01-01
Animal models have greatly enriched our understanding of the molecular mechanisms of numerous types of cancers. Gastric cancer is one of the most common cancers worldwide, with a poor prognosis and high incidence of drug-resistance. However, most inbred strains of mice have proven resistant to gastric carcinogenesis. To establish useful models which mimic human gastric cancer phenotypes, investigators have utilized animals infected with Helicobacter species and treated with carcinogens. In addition, by exploiting genetic engineering, a variety of transgenic and knockout mouse models of gastric cancer have emerged, such as INS-GAS mice and TFF1 knockout mice. Investigators have used the combination of carcinogens and gene alteration to accelerate gastric cancer development, but rarely do mouse models show an aggressive and metastatic gastric cancer phenotype that could be relevant to preclinical studies, which may require more specific targeting of gastric progenitor cells. Here, we review current gastric carcinogenesis mouse models and provide our future perspectives on this field. PMID:24216700
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Mouse models of Fanconi anemia
International Nuclear Information System (INIS)
Parmar, Kalindi; D'Andrea, Alan; Niedernhofer, Laura J.
2009-01-01
Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.
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Mouse models of Fanconi anemia
Energy Technology Data Exchange (ETDEWEB)
Parmar, Kalindi; D' Andrea, Alan [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Niedernhofer, Laura J., E-mail: niedernhoferl@upmc.edu [Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine and Cancer Institute, 5117 Centre Avenue, Hillman Cancer Center, Research Pavilion 2.6, Pittsburgh, PA 15213-1863 (United States)
2009-07-31
Fanconi anemia is a rare inherited disease characterized by congenital anomalies, growth retardation, aplastic anemia and an increased risk of acute myeloid leukemia and squamous cell carcinomas. The disease is caused by mutation in genes encoding proteins required for the Fanconi anemia pathway, a response mechanism to replicative stress, including that caused by genotoxins that cause DNA interstrand crosslinks. Defects in the Fanconi anemia pathway lead to genomic instability and apoptosis of proliferating cells. To date, 13 complementation groups of Fanconi anemia were identified. Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia. This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability.
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International Nuclear Information System (INIS)
Bhattacharyya, M.H.; Peterson, D.P.; Lindenbaum, A.
1978-01-01
Rats received an intravenous injection of 0.1 μCi of 239 Pu-citrate (approximately 0.5 μCi/kg). At 24 hr after Pu injection, the bile ducts were cannulated and diethylenetriaminepentaacetic acid (DTPA, 0.25 mmole/kg) was injected intravenously. The amount of Pu appearing in the bile during the first 24 hr after DTPA injection was determined. In addition, the decrease in Pu content of the liver 24 hr after DTPA administration was measured in both bile duct-cannulated and noncannulated rats and compared to the amount of Pu appearing in the bile. Bile collected from control rats receiving saline instead of DTPA contained 0.40 +- 0.08 nCi of Pu (mean +- SE, n = 3), while bile collected for 24 hr after DTPA administration contained 7.2 +- 0.4 nCi Pu (mean +- SE, n = 6). Thus, DTPA administration brought about a striking increase in biliary Pu excretion. The mean decrease in liver Pu content 24 hr after DTPA administration to rats whole bile ducts were not cannulated was 7.4 +- 1.4 nCi (mean +- SE, n = 6); the corresponding decrease calculated for three bile duct-cannulated rats was 7.2 +- 1.3 nCi. We have demonstrated, therefore, a nearly exact correspondence between the amount of Pu removed from the liver and that appearing in the bile following DTPA administration to the rat
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Alcohol Exposure Alters Mouse Lung Inflammation in Response to Inhaled Dust
Directory of Open Access Journals (Sweden)
Jill A. Poole
2012-07-01
Full Text Available Alcohol exposure is associated with increased lung infections and decreased mucociliary clearance. Occupational workers exposed to dusts from concentrated animal feeding operations (CAFOs are at risk for developing chronic inflammatory lung diseases. Agricultural worker co-exposure to alcohol and organic dust has been established, although little research has been conducted on the combination effects of alcohol and organic dusts on the lung. Previously, we have shown in a mouse model that exposure to hog dust extract (HDE collected from a CAFO results in the activation of protein kinase C (PKC, elevated lavage fluid cytokines/chemokines including interleukin-6 (IL-6, and the development of significant lung pathology. Because alcohol blocks airway epithelial cell release of IL-6 in vitro, we hypothesized that alcohol exposure would alter mouse lung inflammatory responses to HDE. To test this hypothesis, C57BL/6 mice were fed 20% alcohol or water ad libitum for 6 weeks and treated with 12.5% HDE by intranasal inhalation method daily during the final three weeks. Bronchoalveolar lavage fluid (BALF, tracheas and lungs were collected. HDE stimulated a 2–4 fold increase in lung and tracheal PKCε (epsilon activity in mice, but no such increase in PKCε activity was observed in dust-exposed mice fed alcohol. Similarly, alcohol-fed mice demonstrated significantly less IL-6 in lung lavage in response to dust than that observed in control mice instilled with HDE. TNFα levels were also inhibited in the alcohol and HDE-exposed mouse lung tissue as compared to the HDE only exposed group. HDE-induced lung inflammatory aggregates clearly present in the tissue from HDE only exposed animals were not visually detectable in the HDE/alcohol co-exposure group. Statistically significant weight reductions and 20% mortality were also observed in the mice co-exposed to HDE and alcohol. These data suggest that alcohol exposure depresses the ability
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International Nuclear Information System (INIS)
Wang, Yingyan; Wang, Wei; Wang, Siyan; Wang, Jiarui; Shao, Shujuan; Wang, Qi
2008-01-01
Chemotherapy resistance remains a major obstacle for the treatment of small cell lung cancer (SCLC). Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum chaperone, plays a critical role in chemotherapy resistance in some cancers. However, whether the suppression of the chaperone can enhance the sensitivity of chemotherapy in SCLC is still unclear. The SCLC NCI-H446 cells were divided into three groups: BAPTA-AM→A23187-treated group, A23187-treated group and control-group. Immunofluorescence, western blot and RT-PCR were used to assess the expression of GRP78 at both protein and mRNA levels. Cell apoptosis and the cell cycle distributions of the cells were analyzed by flow cytometry in order to evaluate the therapeutic sensitivity to VP-16. The expression of GRP78 at both protein and mRNA levels in the BAPTA-AM→A23187-treated cells dramatically decreased as compared to that in both A23187-treated and control groups. After treatment by VP-16, the percentage of apoptotic cells in BAPTA-AM→A23187-treated cells were: 33.4 ± 1.01%, 48.2 ± 1.77%, 53.0 ± 1.43%, 56.5 ± 2.13%, respectively, corresponding to the concentrations of BAPTA-AM 10, 15, 25, 40 μM, which was statistically significant high in comparison with the A23187-treated group and untreated-group (7.18 ± 1.03% and 27.8 ± 1.45%, respectively, p < 0.05). The results from analysis of cell cycle distribution showed that there was a significantly decreased in G 1 phase and a dramatically increased in S phase for the BAPTA-AM→A23187-treated cells as compared with the untreated cells. BAPTA-AM is a strong inhibitor of GRP78 in the NCI-H446 cell line, the down-regulation of GRP78 can significantly increase the sensitivity to VP-16. The suppression of GRP78 may offer a new surrogated therapeutic approach to the clinical management of lung cancer
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Roth, Andrew; Kyzar, Evan J; Cachat, Jonathan; Stewart, Adam Michael; Green, Jeremy; Gaikwad, Siddharth; O'Leary, Timothy P; Tabakoff, Boris; Brown, Richard E; Kalueff, Allan V
2013-01-10
Rodent self-grooming is an important, evolutionarily conserved behavior, highly sensitive to pharmacological and genetic manipulations. Mice with aberrant grooming phenotypes are currently used to model various human disorders. Therefore, it is critical to understand the biology of grooming behavior, and to assess its translational validity to humans. The present in-silico study used publicly available gene expression and behavioral data obtained from several inbred mouse strains in the open-field, light-dark box, elevated plus- and elevated zero-maze tests. As grooming duration differed between strains, our analysis revealed several candidate genes with significant correlations between gene expression in the brain and grooming duration. The Allen Brain Atlas, STRING, GoMiner and Mouse Genome Informatics databases were used to functionally map and analyze these candidate mouse genes against their human orthologs, assessing the strain ranking of their expression and the regional distribution of expression in the mouse brain. This allowed us to identify an interconnected network of candidate genes (which have expression levels that correlate with grooming behavior), display altered patterns of expression in key brain areas related to grooming, and underlie important functions in the brain. Collectively, our results demonstrate the utility of large-scale, high-throughput data-mining and in-silico modeling for linking genomic and behavioral data, as well as their potential to identify novel neural targets for complex neurobehavioral phenotypes, including grooming. Copyright © 2012 Elsevier Inc. All rights reserved.
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Mouse myocardial first-pass perfusion MR imaging
Coolen, Bram F.; Moonen, Rik P. M.; Paulis, Leonie E. M.; Geelen, Tessa; Nicolay, Klaas; Strijkers, Gustav J.
2010-01-01
A first-pass myocardial perfusion sequence for mouse cardiac MRI is presented. A segmented ECG-triggered acquisition combined with parallel imaging acceleration was used to capture the first pass of a Gd-DTPA bolus through the mouse heart with a temporal resolution of 300-400 msec. The method was
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Mouse adenovirus type 1 infection of macrophages
Ashley, S.L.; Welton, A.R.; Harwood, K.M.; Rooijen, van N.; Spindler, K.R.
2009-01-01
Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus.
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Permissivity of the NCI-60 cancer cell lines to oncolytic Vaccinia Virus GLV-1h68
International Nuclear Information System (INIS)
Ascierto, Maria Libera; Bedognetti, Davide; Uccellini, Lorenzo; Rossano, Fabio; Ascierto, Paolo A; Stroncek, David F; Restifo, Nicholas P; Wang, Ena; Szalay, Aladar A; Marincola, Francesco M; Worschech, Andrea; Yu, Zhiya; Adams, Sharon; Reinboth, Jennifer; Chen, Nanhai G; Pos, Zoltan; Roychoudhuri, Rahul; Di Pasquale, Giovanni
2011-01-01
Oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. We previously described GLV-1h68, a modified Vaccinia Virus with exclusive tropism for tumor cells, and we observed a cell line-specific relationship between the ability of GLV-1h68 to replicate in vitro and its ability to colonize and eliminate tumor in vivo. In the current study we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of cell lines. Selected cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain. In order to identify correlates of permissity to viral infection, we measured transcriptional profiles of the cell lines prior infection. We observed highly heterogeneous permissivity to VACV infection amongst the cell lines. The heterogeneity of permissivity was independent of tissue with the exception of B cell derivation. Cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain and a significant correlation was found suggesting a common permissive phenotype. While no clear transcriptional pattern could be identified as predictor of permissivity to infection, some associations were observed suggesting multifactorial basis permissivity to viral infection. Our findings have implications for the design of oncolytic therapies for cancer and offer insights into the nature of permissivity of tumor cells to viral infection
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In memoriam: an appreciation for the NCI R25T cancer education and career development program.
Chang, Shine
2014-06-01
On September 7, 2013, the NCI R25T award mechanism ended its final "receipt/review/award cycle" after more than two decades shaping the cancer prevention and control workforce. Created in 1991 to respond to a national shortage of cancer prevention and control researchers, the R25T supported innovative institutional programs with specialized curricula preparing individuals for careers as independent scientists for the field. Required elements ensured developing transdisciplinary sensibilities and skills highly suited to team science, including conducting collaborative research with mentors of complementary expertise. R25Ts provided trainee stipends, research, education, and travel funds at levels far higher than T32 National Service Research Awards to attract individuals from diverse disciplines. Graduates are faculty at all academic ranks, and hold leadership positions such as associate directors of cancer prevention and control. Beyond its trainees, R25Ts also recruited into the field other students exposed through courses in specialized prevention curricula, as well as course instructors and trainee mentors, who did not initially consider their work to be relevant to cancer prevention. Although advances are being achieved, prevention efforts are not yet fully realized, and currently unknown is the impact on the workforce of terminating the R25T, including whether it is another barrier to preventing cancer. ©2014 American Association for Cancer Research.
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International Nuclear Information System (INIS)
Gao, Xiugong; Sprando, Robert L.; Yourick, Jeffrey J.
2015-01-01
Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds
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Energy Technology Data Exchange (ETDEWEB)
Gao, Xiugong, E-mail: xiugong.gao@fda.hhs.gov; Sprando, Robert L.; Yourick, Jeffrey J.
2015-08-15
Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds.
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Directory of Open Access Journals (Sweden)
Yan-Der Hsuuw
2013-01-01
Full Text Available Ochratoxin A (OTA, a mycotoxin found in many foods worldwide, causes nephrotoxicity, hepatotoxicity, and immunotoxicity, both in vitro and in vivo. In the present study, we explored the cytotoxic effects exerted by OTA on the blastocyst stage of mouse embryos, on subsequent embryonic attachment, on outgrowth in vitro, and following in vivo implantation via embryo transfer. Mouse blastocysts were incubated with or without OTA (1, 5, or 10 μM for 24 h. Cell proliferation and growth were investigated using dual differential staining; apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL assay; and embryo implantation and post-implantation development were assessed by examination of in vitro growth and the outcome of in vivo embryo transfer, respectively. Blastocysts treated with 10 μM OTA displayed a significantly increased level of apoptosis and a reduction in total cell number. Interestingly, we observed no marked difference in implantation success rate between OTA-pretreated and control blastocysts either during in vitro embryonic development (following implantation in a fibronectin-coated culture dish or after in vivo embryo transfer. However, in vitro treatment with 10 μM OTA was associated with increased resorption of post-implantation embryos by the mouse uterus, and decreased fetal weight upon embryo transfer. Our results collectively indicate that in vitro exposure to OTA triggers apoptosis and retards early post-implantation development after transfer of embryos to host mice. In addition, OTA induces apoptosis-mediated injury of mouse blastocysts, via reactive oxygen species (ROS generation, and promotes mitochondrion-dependent apoptotic signaling processes that impair subsequent embryonic development.
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Mouse myocardial first-pass perfusion MR imaging
Coolen, B.F.; Moonen, R.P.M.; Paulis, L.E.M.; Geelen, T.; Nicolay, K.; Strijkers, G.J.
2010-01-01
A first-pass myocardial perfusion sequence for mouse cardiac MRI is presented. A segmented ECG-triggered acquisition combined with parallel imaging acceleration was used to capture the first pass of a Gd-DTPA bolus through the mouse heart with a temporal resolution of 300–400 msec. The method was
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Immunologic analyses of mouse cystathionase in normal and leukemic cells
International Nuclear Information System (INIS)
Bikel, I.; Faibes, D.; Uren, J.R.; Livingston, D.M.
1978-01-01
Rabbit antisera have been raised against mouse liver cystathionase and shown to possess enzyme neutralizing activity. Agar gel double immunodiffusion analyses demonstrated that both mouse liver cystathionase and rat liver cystathionase react with the antisera, the latter enzyme being completely cross-reactive with the former. Following radioiodination of the purified rat liver enzyme, a double antibody radioimmunoassay was developed in which greater than 90% of the labeled protein could be specifically precipitated with the anti-mouse cystathionase antibodies. In this test the purified rat liver and mouse liver enzymes were virtually indistinguishable, generating superimposable competition displacement curves on a protein mass basis. These results indicate that both enzymes are immunologically identical, thus validating the use of the rat in lieu of the murine liver enzyme as radiolabeled tracer in an assay for mouse cystathionase. In addition, competition radioimmunoassays demonstrated that the immunological reactivities of both the purified rat liver and mouse liver enzymes were equally heat sensitive. The sensitivity of the assay was determined to be 1 ng of enzyme protein/0.22 mL of assay mixture, and the assay could be used to detect the presence of enzyme protein in tissue homogenates of single mouse organs. Mouse or rat cross-reactivity with human liver cystathionase was incomplete; but, with the exception of heart and spleen, parallel radioimmunoassay competition displacement curves were obtained for cystathionase from different mouse organs including thymus. Extracts of 7-, 9-, and 10-month-old spontaneous AKR mouse thymomas were tested in the radioimmunoassay along with extracts of age-matched thymuses which were grossly tumor free. A reaction of nonidentity was observed for all of the tumor extracts while a reaction identical with that of the pure liver enzyme was found with all of the normal thymus extracts
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International Nuclear Information System (INIS)
Uno, Shigeyuki; Endo, Kaori; Ishida, Yuji; Tateno, Chise; Makishima, Makoto; Yoshizato, Katsutoshi; Nebert, Daniel W.
2009-01-01
Human and rodent cytochrome P450 (CYP) enzymes sometimes exhibit striking species-specific differences in substrate preference and rate of metabolism. Human risk assessment of CYP substrates might therefore best be evaluated in the intact mouse by replacing mouse Cyp genes with human CYP orthologs; however, how 'human-like' can human gene expression be expected in mouse tissues? Previously a bacterial-artificial-chromosome-transgenic mouse, carrying the human CYP1A1 C YP1A2 locus and lacking the mouse Cyp1a1 and Cyp1a2 orthologs, was shown to express robustly human dioxin-inducible CYP1A1 and basal versus inducible CYP1A2 (mRNAs, proteins, enzyme activities) in each of nine mouse tissues examined. Chimeric mice carrying humanized liver have also been generated, by transplanting human hepatocytes into a urokinase-type plasminogen activator(+/+) s evere-combined-immunodeficiency (uPA/SCID) line with most of its mouse hepatocytes ablated. Herein we compare basal and dioxin-induced CYP1A mRNA copy numbers, protein levels, and four enzymes (benzo[a]pyrene hydroxylase, ethoxyresorufin O-deethylase, acetanilide 4-hydroxylase, methoxyresorufin O-demethylase) in liver of these two humanized mouse lines versus wild-type mice; we also compare these same parameters in mouse Hepa-1c1c7 and human HepG2 hepatoma-derived established cell lines. Most strikingly, mouse liver CYP1A1-specific enzyme activities are between 38- and 170-fold higher than human CYP1A1-specific enzyme activities (per unit of mRNA), whereas mouse versus human CYP1A2 enzyme activities (per unit of mRNA) are within 2.5-fold of one another. Moreover, both the mouse and human hepatoma cell lines exhibit striking differences in CYP1A mRNA levels and enzyme activities. These findings are relevant to risk assessment involving human CYP1A1 and CYP1A2 substrates, when administered to mice as environmental toxicants or drugs.
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Effect of Duplicate Genes on Mouse Genetic Robustness: An Update
Directory of Open Access Journals (Sweden)
Zhixi Su
2014-01-01
Full Text Available In contrast to S. cerevisiae and C. elegans, analyses based on the current knockout (KO mouse phenotypes led to the conclusion that duplicate genes had almost no role in mouse genetic robustness. It has been suggested that the bias of mouse KO database toward ancient duplicates may possibly cause this knockout duplicate puzzle, that is, a very similar proportion of essential genes (PE between duplicate genes and singletons. In this paper, we conducted an extensive and careful analysis for the mouse KO phenotype data and corroborated a strong effect of duplicate genes on mouse genetics robustness. Moreover, the effect of duplicate genes on mouse genetic robustness is duplication-age dependent, which holds after ruling out the potential confounding effect from coding-sequence conservation, protein-protein connectivity, functional bias, or the bias of duplicates generated by whole genome duplication (WGD. Our findings suggest that two factors, the sampling bias toward ancient duplicates and very ancient duplicates with a proportion of essential genes higher than that of singletons, have caused the mouse knockout duplicate puzzle; meanwhile, the effect of genetic buffering may be correlated with sequence conservation as well as protein-protein interactivity.
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Cultures of preimplantation mouse embryos
International Nuclear Information System (INIS)
Streffer, C.; Molls, M.
1987-01-01
In the preimplantation mouse embryos the chromosomal damage develops through several postradiation cell cycles and mitoses. New chromosome aberrations are seen during the second and third postradiation mitoses. Also, more micronuclei appear during later postradiation interphases. This is in agreement with the assumption that unrepaired chromosomal radiation damage develops during the cell generation cycle to such a form (i.e. double-strand breaks in DNA) that chromosomal breaks occur. This proposition is strengthened by the observation that radiation-induced damage is more rapidly expressed after neutron exposure (first or second postradiation mitosis) than after exposure to X rays at the one- or two-cell stage. The preimplantation mouse embryo culture is an inviting system for additional studies at the molecular level, especially now that within the last few years more sensitive methods have been developed for study of DNA and protein structure, regulation, and synthesis. The results from these studies of cultures of preimplantation mouse embryos present a favorable case for the study of complex biological systems under very defined conditions in vitro for extrapolation to effects in vivo
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{gamma}-Radiation-induced follicular degeneration in the prepubertal mouse ovary
Energy Technology Data Exchange (ETDEWEB)
Lee, Chang Joo [Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Yoon, Yong-Dal [Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)]. E-mail: ydyoon@hanyang.ac.kr
2005-10-15
Prepubertal mice were whole-body irradiated with a mean lethal dose (LD{sub 50}) of {gamma}-radiation using a {sup 60}Co source with a total dose of 7.2 Gy and a dose rate of 12.0 cGy/min. At day 0 before the irradiation and at day 1, 2, and 3 after the irradiation, the ovaries were collected and the morphological changes were assessed. The ratios (%) of atretic or polymorphonuclear leukocytes (neutrophil)-infiltrated follicles in the largest cross sections were calculated. In the early atretic follicle of the control mouse ovary, both apoptotic and mitotic cells were observed and occasionally neutrophils were infiltrated into the follicle cavity. However, in the atretic follicles 2 days post-irradiation, numerous cell fragments, apoptotic cells and bodies, and especially, a number of neutrophils were observed. In the non-irradiated control, the ratios of atretic follicles were 58.0 {+-} 8.6 and 27.3 {+-} 11.2 (mean {+-} S.E.M.) in antral and preantral follicles, respectively. The ratios of the number of antral and preantral follicles with one or more neutrophils to the total number of atretic follicles were 29.3 {+-} 12.0. At 2 days post-irradiation, the ratios of atretic follicles were increased to 94.0 {+-} 3.4 and 86.9 {+-} 7.6 in antral and preantral follicles, respectively. The ratios of neutrophil-containing follicles among the atretic one were increased to 65.9 {+-} 11.5 and 57.8 {+-} 15.4 at 2 and 3 days after the irradiation, respectively. Taken together, the present results show that {gamma}-radiation induces apoptotic and inflammatory degeneration of mouse ovarian follicles. Besides, neutrophils may be involved in the acute atretic degeneration in {gamma}-irradiated mouse ovarian follicles.
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Energy Technology Data Exchange (ETDEWEB)
Leonardi, Roberta [St. Jude Children' s Research Hospital, Memphis, TN (United States); Zhang, Yong-Mei [St. Jude Children' s Research Hospital, Memphis, TN (United States); Lykidis, Athanasios [DOE Joint Genome Inst., Walnut Creek, CA (United States); Rock, Charles O. [St. Jude Children' s Research Hospital, Memphis, TN (United States); Jackowski, Suzanne [St. Jude Children' s Research Hospital, Memphis, TN (United States)
2007-09-07
Coenzyme A (CoA) biosynthesis is initiated by pantothenatekinase (PanK) and CoA levels are controlled through differentialexpression and feedback regulation of PanK isoforms. PanK2 is amitochondrial protein in humans, but comparative genomics revealed thatacquisition of a mitochondrial targeting signal was limited to primates.Human and mouse PanK2 possessed similar biochemical properties, withinhibition by acetylCoA and activation by palmitoylcarnitine. Mouse PanK2localized in the cytosol, and the expression of PanK2 was higher in humanbrain compared to mouse brain. Differences in expression and subcellularlocalization should be considered in developing a mouse model for humanPanK2 deficiency.
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Supporting Informed Decision Making - Center for Research Strategy
CRS conducts portfolio analyses and collects data on scientific topics, funding mechanisms, and investigator characteristics to help NCI leadership make data-driven decisions about the scientific research enterprise.
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Interactions of mouse pinworms and trichomonads
Choutková, Jana
2012-01-01
Oxyurid nematodes Aspiculuris tetraptera and Syphacia obvelata are both common mouse intestinal parasites; in the same location several species of trichomonads occur. Tritrichomonas muris is the most often found, but there are also some others: Tritrichomonas minuta, Pentatrichomonas hominis or Hexamastix muris. It is known that, under some circumstances, trichomonads can be found in the intestine of mouse pinworms, as reported by Theiler and Farber (1936) for T. muris in A. tetraptera and S....
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Accesion number Protein name ENOA_MOUSE Alpha-enolase ...
Indian Academy of Sciences (India)
Sandra Feijoo Bandin
Mitochondrial inner membrane protein. CMC1_MOUSE. Calcium-binding mitochondrial carrier protein Aralar1. CMC2_MOUSE. Calcium-binding mitochondrial carrier protein Aralar2. Biological process. Metabolic process. Glycolysis. Lipid metabolism. Respiratory electron transport chain. Others. Calcium ion homeostasis.
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Zhou, Yingjun; Hong, Fashui; Wang, Ling
2017-11-01
Exposure to fine particulate matter (PM) is known to cause cardiovascular disease. While extensive research has focused on the risk of atmospheric PM to public health, particularly heart disease, limited studies to date have attempted to clarify the molecular mechanisms underlying myocardial cell damage caused by exposure to titanium dioxide nanoparticles (TiO2 NPs). Data from the current investigation showed that TiO2 NPs are deposited in myocardial mitochondria via the blood circulation accompanied by obvious ultrastructural changes and impairment of mitochondrial structure and function in mouse myocardial cells, including reduction in mitochondrial membrane potential and ATP production, aggravation of oxidative stress along with increased levels of reactive oxygen species, malondialdehyde and protein carbonyl, and decreased glutathione content and enzymatic activities, including superoxide dismutase and glutathione peroxidase. Furthermore, TiO2 NPs induced a significant decrease in the activities of complex I, complex II, complex III, complex IV, succinate dehydrogenase, NADH oxidase, Ca2+-ATPase, Na+/K+-ATPase, and Ca2+/Mg2+-ATPase, and upregulation of cytokine expression (including cytochrome c, caspase-3, and p-JNK) in mitochondria-mediated apoptosis while downregulating Bcl-2 expression in mouse myocardial cells. Our results collectively indicate that chronic exposure to TiO2 NPs induces damage in mitochondrial structure and function as well as mitochondria-mediated apoptosis in mouse myocardial cells, which may be closely associated with heart disease in animals and humans.
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Characterization and mapping of the mouse NDP (Norrie disease) locus (Ndp).
Battinelli, E M; Boyd, Y; Craig, I W; Breakefield, X O; Chen, Z Y
1996-02-01
Norrie disease is a severe X-linked recessive neurological disorder characterized by congenital blindness with progressive loss of hearing. Over half of Norrie patients also manifest different degrees of mental retardation. The gene for Norrie disease (NDP) has recently been cloned and characterized. With the human NDP cDNA, mouse genomic phage libraries were screened for the homolog of the gene. Comparison between mouse and human genomic DNA blots hybridized with the NDP cDNA, as well as analysis of phage clones, shows that the mouse NDP gene is 29 kb in size (28 kb for the human gene). The organization in the two species is very similar. Both have three exons with similar-sized introns and identical exon-intron boundaries between exon 2 and 3. The mouse open reading frame is 393 bp and, like the human coding sequence, is encoded in exons 2 and 3. The absence of six nucleotides in the second mouse exon results in the encoded protein being two amino acids smaller than its human counterpart. The overall homology between the human and mouse NDP protein is 95% and is particularly high (99%) in exon 3, consistent with the apparent functional importance of this region. Analysis of transcription initiation sites suggests the presence of multiple start sites associated with expression of the mouse NDP gene. Pedigree analysis of an interspecific mouse backcross localizes the mouse NDP gene close to Maoa in the conserved segment, which runs from CYBB to PFC in both human and mouse.
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Network statistics of genetically-driven gene co-expression modules in mouse crosses
Directory of Open Access Journals (Sweden)
Marie-Pier eScott-Boyer
2013-12-01
Full Text Available In biology, networks are used in different contexts as ways to represent relationships between entities, such as for instance interactions between genes, proteins or metabolites. Despite progress in the analysis of such networks and their potential to better understand the collective impact of genes on complex traits, one remaining challenge is to establish the biologic validity of gene co-expression networks and to determine what governs their organization. We used WGCNA to construct and analyze seven gene expression datasets from several tissues of mouse recombinant inbred strains (RIS. For six out of the 7 networks, we found that linkage to module QTLs (mQTLs could be established for 29.3% of gene co-expression modules detected in the several mouse RIS. For about 74.6% of such genetically-linked modules, the mQTL was on the same chromosome as the one contributing most genes to the module, with genes originating from that chromosome showing higher connectivity than other genes in the modules. Such modules (that we considered as genetically-driven had network statistic properties (density, centralization and heterogeneity that set them apart from other modules in the network. Altogether, a sizeable portion of gene co-expression modules detected in mouse RIS panels had genetic determinants as their main organizing principle. In addition to providing a biologic interpretation validation for these modules, these genetic determinants imparted on them particular properties that set them apart from other modules in the network, to the point that they can be predicted to a large extent on the basis of their network statistics.
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van der Geld, Ymke M.; Hellmark, Thomas; Selga, Daina; Heeringa, Peter; Huitema, Minke G.; Limburg, Pieter C.; Kallenberg, Cees G. M.
2007-01-01
Aim: In this study, we employed chimeric human/ mouse Proteinase 3 ( PR3) proteins as tools to induce an autoantibody response to PR3 in rats and mice. Method: Rats and mice were immunised with recombinant human PR3 ( HPR3), recombinant murine PR3 ( mPR3), single chimeric human/ mouse PR3 ( HHm,
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Mouse Genome Informatics (MGI)
U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...
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U.S. Department of Health & Human Services — The Mouse Phenome Database (MPD) has characterizations of hundreds of strains of laboratory mice to facilitate translational discoveries and to assist in selection...
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Gossypol induces pyroptosis in mouse macrophages via a non-canonical inflammasome pathway
International Nuclear Information System (INIS)
Lin, Qiu-Ru; Li, Chen-Guang; Zha, Qing-Bing; Xu, Li-Hui; Pan, Hao; Zhao, Gao-Xiang; Ouyang, Dong-Yun; He, Xian-Hui
2016-01-01
Gossypol, a polyphenolic compound isolated from cottonseeds, has been reported to possess many pharmacological activities, but whether it can influence inflammasome activation remains unclear. In this study, we found that in mouse macrophages, gossypol induced cell death characterized by rapid membrane rupture and robust release of HMGB1 and pro-caspase-11 comparable to ATP treatment, suggesting an induction of pyroptotic cell death. Unlike ATP, gossypol induced much low levels of mature interleukin-1β (IL-1β) secretion from mouse peritoneal macrophages primed with LPS, although it caused pro-IL-1β release similar to that of ATP. Consistent with this, activated caspase-1 responsible for pro-IL-1β maturation was undetectable in gossypol-treated peritoneal macrophages. Besides, RAW 264.7 cells lacking ASC expression and caspase-1 activation also underwent pyroptotic cell death upon gossypol treatment. In further support of pyroptosis induction, both pan-caspase inhibitor and caspase-1 subfamily inhibitor, but not caspase-3 inhibitor, could sharply suppress gossypol-induced cell death. Other canonical pyroptotic inhibitors, including potassium chloride and N-acetyl-L-cysteine, could suppress ATP-induced pyroptosis but failed to inhibit or even enhanced gossypol-induced cell death, whereas nonspecific pore-formation inhibitor glycine could attenuate this process, suggesting involvement of a non-canonical pathway. Of note, gossypol treatment eliminated thioglycollate-induced macrophages in the peritoneal cavity with recruitment of other leukocytes. Moreover, gossypol administration markedly decreased the survival of mice in a bacterial sepsis model. Collectively, these results suggested that gossypol induced pyroptosis in mouse macrophages via a non-canonical inflammasome pathway, which raises a concern for its in vivo cytotoxicity to macrophages. - Highlights: • Gossypol induces pyroptosis in mouse peritoneal and RAW 264.7 macrophages. • In LPS
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Gossypol induces pyroptosis in mouse macrophages via a non-canonical inflammasome pathway
Energy Technology Data Exchange (ETDEWEB)
Lin, Qiu-Ru; Li, Chen-Guang [Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Zha, Qing-Bing [Department of Fetal Medicine, The First Affiliated Hospital of Jinan University, Guangzhou 510632 (China); Xu, Li-Hui [Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Pan, Hao; Zhao, Gao-Xiang [Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Ouyang, Dong-Yun, E-mail: dongyun1967@aliyun.com [Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); He, Xian-Hui, E-mail: thexh@jnu.edu.cn [Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China)
2016-02-01
Gossypol, a polyphenolic compound isolated from cottonseeds, has been reported to possess many pharmacological activities, but whether it can influence inflammasome activation remains unclear. In this study, we found that in mouse macrophages, gossypol induced cell death characterized by rapid membrane rupture and robust release of HMGB1 and pro-caspase-11 comparable to ATP treatment, suggesting an induction of pyroptotic cell death. Unlike ATP, gossypol induced much low levels of mature interleukin-1β (IL-1β) secretion from mouse peritoneal macrophages primed with LPS, although it caused pro-IL-1β release similar to that of ATP. Consistent with this, activated caspase-1 responsible for pro-IL-1β maturation was undetectable in gossypol-treated peritoneal macrophages. Besides, RAW 264.7 cells lacking ASC expression and caspase-1 activation also underwent pyroptotic cell death upon gossypol treatment. In further support of pyroptosis induction, both pan-caspase inhibitor and caspase-1 subfamily inhibitor, but not caspase-3 inhibitor, could sharply suppress gossypol-induced cell death. Other canonical pyroptotic inhibitors, including potassium chloride and N-acetyl-L-cysteine, could suppress ATP-induced pyroptosis but failed to inhibit or even enhanced gossypol-induced cell death, whereas nonspecific pore-formation inhibitor glycine could attenuate this process, suggesting involvement of a non-canonical pathway. Of note, gossypol treatment eliminated thioglycollate-induced macrophages in the peritoneal cavity with recruitment of other leukocytes. Moreover, gossypol administration markedly decreased the survival of mice in a bacterial sepsis model. Collectively, these results suggested that gossypol induced pyroptosis in mouse macrophages via a non-canonical inflammasome pathway, which raises a concern for its in vivo cytotoxicity to macrophages. - Highlights: • Gossypol induces pyroptosis in mouse peritoneal and RAW 264.7 macrophages. • In LPS
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Korstanje, Ron; Desai, Jigar; Lazar, Gloria; King, Benjamin; Rollins, Jarod; Spurr, Melissa; Joseph, Jamie; Kadambi, Sindhuja; Li, Yang; Cherry, Allison; Matteson, Paul G.; Paigen, Beverly; Millonig, James H.
Korstanje R, Desai J, Lazar G, King B, Rollins J, Spurr M, Joseph J, Kadambi S, Li Y, Cherry A, Matteson PG, Paigen B, Millonig JH. Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects. Physiol Genomics 35:
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Wang, Feng; Jiang, Rosie; Takahashi, Keiko; Gore, John; Harris, Raymond C; Takahashi, Takamune; Quarles, C Chad
2014-11-01
The purpose of this study is to evaluate the utility of high-resolution non-invasive endogenous high-field MRI methods for the longitudinal structural and quantitative assessments of mouse kidney disease using the model of unilateral ureter obstruction (UUO). T1-weighted, T2-weighted and magnetization transfer (MT) imaging protocols were optimized to improve the regional contrast in mouse kidney. Conventional T1 and T2 weighted images were collected in UUO mice on day 0 (~3h), day 1, day 3 and day 6 after injury, on a 7 T small animal MRI system. Cortical and medullary thickness, corticomedullary contrast and Magnetization Transfer Ratio (MTR) were assessed longitudinally. Masson trichrome staining was used to histologically assess changes in tissue microstructure. Over the course of UUO progression there were significant (prenal cortical and medullary atrophy, cortical-medullary differentiation and MTR changes provide an endogenous, non-invasive and quantitative evaluation of renal morphology and tissue composition during UUO progression. Copyright © 2014 Elsevier Inc. All rights reserved.
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Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.
2014-03-01
Consumption of alcohol during pregnancy can be severely detrimental to the development of the brain in fetuses. This study explores the usage of optical coherence tomography (OCT) to the study the effects of maternal consumption of ethanol on brain development in mouse fetuses. On gestational day 14.5, fetuses were collected and fixed in 4% paraformaldehyde. A swept-source OCT (SSOCT) system was used to acquire 3D images of the brain of ethanol-exposed and control fetuses. The volume of right and left brain ventricles were measured and used to compare between ethanol-exposed and control fetuses. A total of 5 fetuses were used for each of the two groups. The average volumes of the right and left ventricles were measured to be 0.35 and 0.15 mm3 for ethanol-exposed and control fetuses, respectively. The results demonstrated that there is an alcohol-induced developmental delay in mouse fetal brains.
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Behavioral phenotypes of genetic mouse models of autism.
Kazdoba, T M; Leach, P T; Crawley, J N
2016-01-01
More than a hundred de novo single gene mutations and copy-number variants have been implicated in autism, each occurring in a small subset of cases. Mutant mouse models with syntenic mutations offer research tools to gain an understanding of the role of each gene in modulating biological and behavioral phenotypes relevant to autism. Knockout, knockin and transgenic mice incorporating risk gene mutations detected in autism spectrum disorder and comorbid neurodevelopmental disorders are now widely available. At present, autism spectrum disorder is diagnosed solely by behavioral criteria. We developed a constellation of mouse behavioral assays designed to maximize face validity to the types of social deficits and repetitive behaviors that are central to an autism diagnosis. Mouse behavioral assays for associated symptoms of autism, which include cognitive inflexibility, anxiety, hyperactivity, and unusual reactivity to sensory stimuli, are frequently included in the phenotypic analyses. Over the past 10 years, we and many other laboratories around the world have employed these and additional behavioral tests to phenotype a large number of mutant mouse models of autism. In this review, we highlight mouse models with mutations in genes that have been identified as risk genes for autism, which work through synaptic mechanisms and through the mTOR signaling pathway. Robust, replicated autism-relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
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Endonucleases : new tools to edit the mouse genome
Wijshake, Tobias; Baker, Darren J.; van de Sluis, Bart
2014-01-01
Mouse transgenesis has been instrumental in determining the function of genes in the pathophysiology of human diseases and modification of genes by homologous recombination in mouse embryonic stem cells remains a widely used technology. However, this approach harbors a number of disadvantages, as it
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Rational Design of Mouse Models for Cancer Research
Landgraf, M.; McGovern, J.A.; Friedl, P.; Hutmacher, D.W.
2018-01-01
The laboratory mouse is widely considered as a valid and affordable model organism to study human disease. Attempts to improve the relevance of murine models for the investigation of human pathologies led to the development of various genetically engineered, xenograft and humanized mouse models.
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Directory of Open Access Journals (Sweden)
Xiaoyan Zhang
2013-05-01
Full Text Available Objective(s: Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL can selectively induce apoptosis in tumor cells, more than half of tumors including non-small cell lung cancer (NSCLC exhibit TRAIL-resistance. The purpose of this study was to determine whether subtoxic-dose cisplatin and TRAIL could synergistically enhance apoptosis on NSCLC cells and investigate its underlying mechanisms. Materials and Methods:NCI-H460 and A549 cells were treated with TRAIL alone, cisplatin alone or combination treatment in this study. The cytotoxicity was evaluated according to Sulforhodamine B assay, and apoptosis was examined using Hoechst 33342 staining and flow cytometry. The mRNA and protein levels of TRAIL receptors and apoptotic proteins including caspase-8, caspase-9, Bcl-2 and Bax were determined by RT-PCR and Western blotting, respectively. Results:Our results showed that NCI-H460 cells were sensitive to TRAIL, whereas A549 cells were resistant. However, subtoxic-dose cisplatin could enhance the both cells to TRAIL-mediated cell proliferation inhibition and apoptosis. The underlying mechanisms might be associated with the down-regulation of DcR2 and up-regulation of Caspase-8, Caspase-9 and Bax. Conclusion:Subtoxic-dose cisplatin could enhance both TRAIL- sensitive and TRAIL- resistant NSCLC cells to TRAIL-mediated apoptosis. These findings motivated further studies to evaluate such a combinatory therapeutic strategy against NSCLC in the animal models.
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Communication Framework For the Mionix Naos QG Mouse
DEFF Research Database (Denmark)
Wulff-Jensen, Andreas
2017-01-01
The Mionix Naos QG mouse has multiple sensors integrated. It can record all the metrics native to mice: being scroll, clicks and mouse movements. Moreover, this mouse has heart rate (HR) and Galvanic Skin Response (GSR) sensors embedded. Through Mionics API [1] WebSocket can be used to access all...... or be recorded. Another Unity implementation have been developed as well. This was directly connected to the WebSocket, and has the same properties as the first Unity development. Since two nearly identical implementations were made, the quality of their recordings and data communication were tested. Based...
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A Comprehensive Atlas of the Adult Mouse Penis
Phillips, Tiffany R.; Wright, David K.; Gradie, Paul E.; Johnston, Leigh A.; Pask, Andrew J.
2016-01-01
Mice are routinely used to study the development of the external genitalia and, in particular, the process of male urethral closure. This is because misplacement of the male penile urethra, or hypospadias, is amongst the most common birth defects reported in humans. While mice present a tractable model to study penile development, several structures differ between mice and humans, and there is a lack of consensus in the literature on their annotation and developmental origins. Defining the ontology of the mouse prepuce is especially important for the relevance and interpretation of mouse models of hypospadias to human conditions. We have developed a detailed annotation of the adult mouse penis that addresses these differences and enables an accurate comparison of murine and human hypospadias phenotypes. Through MRI data, gross morphology and section histology, we define the origin of the mouse external and internal prepuces, their relationship to the single human foreskin as well as provide a comprehensive view of the various structures of the mouse penis and their associated muscle attachments within the body. These data are combined to annotate structures in a novel 3D adult penis atlas that can be downloaded, viewed at any angle, and manipulated to examine the relationship of various structures. PMID:26112156
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The Mouse House: a brief history of the ORNL mouse-genetics program, 1947-2009.
Russell, Liane B
2013-01-01
The large mouse genetics program at the Oak Ridge National Laboratory (ORNL) is often remembered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-chromosome's importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a
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Cross-species comparison of aCGH data from mouse and human BRCA1- and BRCA2-mutated breast cancers
International Nuclear Information System (INIS)
Holstege, Henne; Wessels, Lodewyk FA; Nederlof, Petra M; Jonkers, Jos; Beers, Erik van; Velds, Arno; Liu, Xiaoling; Joosse, Simon A; Klarenbeek, Sjoerd; Schut, Eva; Kerkhoven, Ron; Klijn, Christiaan N
2010-01-01
Genomic gains and losses are a result of genomic instability in many types of cancers. BRCA1- and BRCA2-mutated breast cancers are associated with increased amounts of chromosomal aberrations, presumably due their functions in genome repair. Some of these genomic aberrations may harbor genes whose absence or overexpression may give rise to cellular growth advantage. So far, it has not been easy to identify the driver genes underlying gains and losses. A powerful approach to identify these driver genes could be a cross-species comparison of array comparative genomic hybridization (aCGH) data from cognate mouse and human tumors. Orthologous regions of mouse and human tumors that are commonly gained or lost might represent essential genomic regions selected for gain or loss during tumor development. To identify genomic regions that are associated with BRCA1- and BRCA2-mutated breast cancers we compared aCGH data from 130 mouse Brca1 Δ/Δ ;p53 Δ/Δ , Brca2 Δ/Δ ;p53 Δ/Δ and p53 Δ/Δ mammary tumor groups with 103 human BRCA1-mutated, BRCA2-mutated and non-hereditary breast cancers. Our genome-wide cross-species analysis yielded a complete collection of loci and genes that are commonly gained or lost in mouse and human breast cancer. Principal common CNAs were the well known MYC-associated gain and RB1/INTS6-associated loss that occurred in all mouse and human tumor groups, and the AURKA-associated gain occurred in BRCA2-related tumors from both species. However, there were also important differences between tumor profiles of both species, such as the prominent gain on chromosome 10 in mouse Brca2 Δ/Δ ;p53 Δ/Δ tumors and the PIK3CA associated 3q gain in human BRCA1-mutated tumors, which occurred in tumors from one species but not in tumors from the other species. This disparity in recurrent aberrations in mouse and human tumors might be due to differences in tumor cell type or genomic organization between both species. The selection of the oncogenome during
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Ku, Jacqueline M; Sleeman, Mark W; Sobey, Christopher G; Andrews, Zane B; Miller, Alyson A
2016-04-01
The ghrelin gene is expressed in the stomach where it ultimately encodes up to three peptides, namely, acylated ghrelin, des-acylated ghrelin and obestatin, which all have neuroendocrine roles. Recently, the authors' reported that these peptides have important physiological roles in positively regulating vasodilator nitric oxide (NO) production in the cerebral circulation, and may normally suppress superoxide production by the pro-oxidant enzyme, Nox2-NADPH oxidase. To date, the majority of studies using exogenous peptides infer that they may have similar roles in the systemic circulation. Therefore, this study examined whether exogenous and endogenous ghrelin-related peptides modulate NO production and superoxide levels in mouse mesenteric arteries and/or thoracic aorta. Using wire myography, it was found that application of exogenous acylated ghrelin, des-acylated ghrelin or obestatin to mouse thoracic aorta or mesenteric arteries failed to elicit a vasorelaxation response, whereas all three peptides elicited vasorelaxation responses of rat thoracic aorta. Also, none of the peptides modulated mouse aortic superoxide levels as measured by L-012-enhanced chemiluminescence. Next, it was found that NO bioactivity and superoxide levels were unaffected in the thoracic aorta from ghrelin-deficient mice when compared with wild-type mice. Lastly, using novel GHSR-eGFP reporter mice in combination with double-labelled immunofluorescence, no evidence was found for the growth hormone secretagogue receptor (GHSR1a) in the throracic aorta, which is the only functional ghrelin receptor identified to date. Collectively these findings demonstrate that, in contrast to systemic vessels of other species (e.g. rat and human) and mouse cerebral vessels, ghrelin-related peptides do not modulate vasodilator NO production or superoxide levels in mouse systemic arteries. © 2016 John Wiley & Sons Australia, Ltd.
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DEFF Research Database (Denmark)
Sandfeld, Jesper; Jensen, Bente R.
2005-01-01
and three levels of target size were used. All subjects demonstrated a reduced working speed and hit rate at the highest mouse gain (1:8) when the target size was small. The young group had an optimum at mouse gain 1:4. The elderly group was most sensitive to the combination of high mouse gain and small...
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González Morga, Natalia; García Guillamón, Glória; Brando Asensio, Immaculada
2014-01-01
La violència de gènere és un fenomen parcialment visible en la societat del segle XXI. Amb aquest estudi es pretén determinar la prevalença de violència de gènere en dones que van a urgències per altres patologies i relacionar la presència del maltractament psicològic, físic i sexual amb diferents variables sociodemogràfiques per establir el perfil de la dona víctima del maltractament encobert en l’escenari estudiat. Per fer-ho, 151 dones, pacients de l’Hospital General Universitari Morales M...
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Mouse endometrial stromal cells produce basement-membrane components
DEFF Research Database (Denmark)
Wewer, U M; Damjanov, A; Weiss, J
1986-01-01
During mouse pregnancy, uterine stromal cells transform into morphologically distinct decidual cells under the influence of the implanting embryo and a proper hormonal environment. Mechanical stimulation of hormonally primed uterine stromal cells leads to the same morphologic alterations. The dec......During mouse pregnancy, uterine stromal cells transform into morphologically distinct decidual cells under the influence of the implanting embryo and a proper hormonal environment. Mechanical stimulation of hormonally primed uterine stromal cells leads to the same morphologic alterations....... Mouse decidual cells isolated from 6- to 7-day pregnant uteri explanted in vitro continue to synthesize basement-membrane-like extracellular matrix. Using immunohistochemistry and metabolic labeling followed by immunoprecipitation, SDS-PAGE, and fluorography, it was shown that the decidual cells...... to undergo pseudodecidualization. We thus showed that stromal cells from pregnant and nonpregnant mouse uteri synthesize significant amounts of basement-membrane components in vitro, and hence could serve as a good model for the study of normal basement-membrane components....
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Resistance of human and mouse myeloid leukemia cells to UV radiation
International Nuclear Information System (INIS)
Poljak-Blazi, M.; Osmak, M.; Hadzija, M.
1989-01-01
Sensitivity of mouse bone marrow and myeloid leukemia cells and sensitivity of human myeloid leukemia cells to UV light was tested. Criteria were the in vivo colony-forming ability of UV exposed cells and the inhibition of DNA synthesis during post-irradiation incubation for 24 h in vitro. Mouse bone marrow cells irradiated with a small dose of UV light (5 J/m 2 ) and injected into x-irradiated animals did not form hemopoietic colonies on recipient's spleens, and recipients died. However, mouse leukemia cells, after irradiation with higher doses of UV light, retained the ability to form colonies on the spleens, and all recipient mice died with typical symptoms of leukemia. In vitro, mouse bone marrow cells exhibited high sensitivity to UV light compared to mouse myeloid leukemia cells. Human leukemia cells were also resistant to UV light, but more sensitive than mouse leukemia cells. (author)
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van den Brink, Susanne C; Baillie-Johnson, Peter; Balayo, Tina; Hadjantonakis, Anna-Katerina; Nowotschin, Sonja; Turner, David A; Martinez Arias, Alfonso
2014-11-01
Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate into the normal morphogenetic processes, i.e. they are pluripotent. However, although they can be steered to differentiate in vitro into all cell types of the organism, they cannot organise themselves into structures that resemble embryos. When aggregated into embryoid bodies they develop disorganised masses of different cell types with little spatial coherence. An exception to this rule is the emergence of retinas and anterior cortex-like structures under minimal culture conditions. These structures emerge from the cultures without any axial organisation. Here, we report that small aggregates of mESCs, of about 300 cells, self-organise into polarised structures that exhibit collective behaviours reminiscent of those that cells exhibit in early mouse embryos, including symmetry breaking, axial organisation, germ layer specification and cell behaviour, as well as axis elongation. The responses are signal specific and uncouple processes that in the embryo are tightly associated, such as specification of the anteroposterior axis and anterior neural development, or endoderm specification and axial elongation. We discuss the meaning and implications of these observations and the potential uses of these structures which, because of their behaviour, we suggest to call 'gastruloids'. © 2014. Published by The Company of Biologists Ltd.
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In vivo behavior of 111In-DTPA in rat and mouse after intra-ventricular administration
International Nuclear Information System (INIS)
Matsushima, Hiroaki; Kato, Makoto; Sugimura, Yukiharu; Hazue, Masaaki
1977-01-01
In vivo behavior of 111 In-DTPA in rat and mouse after intra-ventricular administration was studied. Thus, 50μCi and 35μCi of 111 In-DTPA was injected intraventricularly to rat and mouse respectively. At specific time intervals, the animals were sacrificed, then distribution in organs was determined by radioactivity counting and autoradiographic method. Urinary and fecal excretion were separately collected and excretion rates were estimated. Metabolites in urine of rat were examined with chromatography. A part of 111 In-DTPA injected intra-ventricularly to the animals migrated to subarachnoid space, then radioactivity in cerebrospinal fluid effused into blood with about 1 hr initial half-life. Blood clearance was also rapid, about 1 hr after administration the blood level reached maximum and then decreased showing an initial half-life of about 1 hr. The predominant excretion route in rat was urinary and about 90% and 5% of administered dose were excreted within 48 hr through urine and feces respectively. Judging from the Rf-value of radioactivity peak on chromatograms, 111 In-DTPA seems to be excreted without suffering any metabolic change. Concerning to the behavior of 111 In-DTPA in male and female rat, no difference was observed, and the distribution pattern of 111 In-DTPA in mouse was similar to that of rat. (auth.)
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Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha
DOKI, Tomoyoshi; TAKANO, Tomomi; HOHDATSU, Tsutomu
2016-01-01
Feline infectious peritonitis (FIP) is a fatal inflammatory disease caused by FIP virus infection. Feline tumor necrosis factor (fTNF)-alpha is closely involved in the aggravation of FIP pathology. We previously described the preparation of neutralizing mouse anti-fTNF-alpha monoclonal antibody (mAb 2–4) and clarified its role in the clinical condition of cats with FIP using in vitro systems. However, administration of mouse mAb 2–4 to cat may lead to a production of feline anti-mouse antibodies. In the present study, we prepared a mouse-feline chimeric mAb (chimeric mAb 2–4) by fusing the variable region of mouse mAb 2–4 to the constant region of feline antibody. The chimeric mAb 2–4 was confirmed to have fTNF-alpha neutralization activity. Purified mouse mAb 2–4 and chimeric mAb 2–4 were repeatedly administered to cats, and the changes in the ability to induce feline anti-mouse antibody response were investigated. In the serum of cats treated with mouse mAb 2–4, feline anti-mouse antibody production was induced, and the fTNF-alpha neutralization effect of mouse mAb 2–4 was reduced. In contrast, in cats treated with chimeric mAb 2–4, the feline anti-mouse antibody response was decreased compared to that of mouse mAb 2–4-treated cats. PMID:27264736
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Single-mass mutations associated with mouse lymphomas
International Nuclear Information System (INIS)
Guerrero, I.; Berman, J.W.; Diamond, L.E.; Newcomb, E.W.; Villasante, A.
1986-01-01
The authors study the induction of mouse lymphomas after treatment with a chemical carcinogen, nitrosomethyl urea (NMU), or with gamma irradiation. The koplan fractionated gamma radiation scheme and an established protocol for NMU tumor formation were chosen as protocols for induction of mouse lymphomas. In both cases, the mice developed thymic lymphomas with up to 90% incidence. In NMU induction, the latency period is shorter than irradiation
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Spallanzani's mouse: a model of restoration and regeneration.
Heber-Katz, E; Leferovich, J M; Bedelbaeva, K; Gourevitch, D
2004-01-01
The ability to regenerate is thought to be a lost phenotype in mammals, though there are certainly sporadic examples of mammalian regeneration. Our laboratory has identified a strain of mouse, the MRL mouse, which has a unique capacity to heal complex tissue in an epimorphic fashion, i.e., to restore a damaged limb or organ to its normal structure and function. Initial studies using through-and-through ear punches showed rapid full closure of the ear holes with cartilage growth, new hair follicles, and normal tissue architecture reminiscent of regeneration seen in amphibians as opposed to the scarring usually seen in mammals. Since the ear hole closure phenotype is a quantitative trait, this has been used to show-through extensive breeding and backcrossing--that the trait is heritable. Such analysis reveals that there is a complex genetic basis for this trait with multiple loci. One of the major phenotypes of the MRL mouse is a potent remodeling response with the absence or a reduced level of scarring. MRL healing is associated with the upregulation of the metalloproteinases MMP-2 and MMP-9 and the downregulation of their inhibitors TIMP-2 and TIMP-3, both present in inflammatory cells such as neutrophils and macrophages. This model has more recently been extended to the heart. In this case, a cryoinjury to the right ventricle leads to near complete scarless healing in the MRL mouse whereas scarring is seen in the control mouse. In the MRL heart, bromodeoxyuridine uptake by cardiomyocytes filling the wound site can be seen 60 days after injury. This does not occur in the control mouse. Function in the MRL heart, as measured by echocardiography, returns to normal.
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Meeting Report: The Twelfth International Mouse Genome Conference
Energy Technology Data Exchange (ETDEWEB)
Manolakou, Katerina; Cross, Sally H.; Simpson, Eleanor H.; Jackson, Ian J.
1998-10-01
The annual International Mouse Genome Conference (IMGC) is where, scientifically speaking, classical mouse genetics meets the relative newcomer of genomics. The 12th meeting took place last October in the delightful Bavarian village of Garmisch-Partenkirchen, and we were greeted by the sight on the mountains of the first snowfall of the season. However the discussions left little time for exploration. Minds of participants in Garmisch were focused by a recent document produced by the NIH and by discussions within other funding agencies worldwide. If implemented, the proposals will further enhance the status of the mouse as the principal model for study of the function of the human genome.
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Methods of in-vivo mouse lung micro-CT
Recheis, Wolfgang A.; Nixon, Earl; Thiesse, Jacqueline; McLennan, Geoffrey; Ross, Alan; Hoffman, Eric
2005-04-01
Micro-CT will have a profound influence on the accumulation of anatomical and physiological phenotypic changes in natural and transgenetic mouse models. Longitudinal studies will be greatly facilitated, allowing for a more complete and accurate description of events if in-vivo studies are accomplished. The purpose of the ongoing project is to establish a feasible and reproducible setup for in-vivo mouse lung micro-computed tomography (μCT). We seek to use in-vivo respiratory-gated μCT to follow mouse models of lung disease with subsequent recovery of the mouse. Methodologies for optimizing scanning parameters and gating for the in-vivo mouse lung are presented. A Scireq flexiVent ventilated the gas-anesthetized mice at 60 breaths/minute, 30 cm H20 PEEP, 30 ml/kg tidal volume and provided a respiratory signal to gate a Skyscan 1076 μCT. Physiologic monitoring allowed the control of vital functions and quality of anesthesia, e.g. via ECG monitoring. In contrary to longer exposure times with ex-vivo scans, scan times for in-vivo were reduced using 35μm pixel size, 158ms exposure time and 18μm pixel size, 316ms exposure time to reduce motion artifacts. Gating via spontaneous breathing was also tested. Optimal contrast resolution was achieved at 50kVp, 200μA, applying an aluminum filter (0.5mm). There were minimal non-cardiac related motion artifacts. Both 35μm and 1μm voxel size images were suitable for evaluation of the airway lumen and parenchymal density. Total scan times were 30 and 65 minutes respectively. The mice recovered following scanning protocols. In-vivo lung scanning with recovery of the mouse delivered reasonable image quality for longitudinal studies, e.g. mouse asthma models. After examining 10 mice, we conclude μCT is a feasible tool evaluating mouse models of lung pathology in longitudinal studies with increasing anatomic detail available for evaluation as one moves from in-vivo to ex-vivo studies. Further developments include automated
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Rivera, Gildardo; Ahmad Shah, Syed Shoaib; Arrieta-Baez, Daniel; Palos, Isidro; Mongue, Antonio; Sánchez-Torres, Luvia Enid
2017-01-01
Quinoxalines display diverse and interesting pharmacological activities as antibacterial, antiviral, antiparasitic and anticancer agents. Particularly, their 1ˏ4-di-N-oxide derivatives have proved to be cytotoxic agents that are active under hypoxic conditions as that of solid tumours. A new series of quinoxaline 1ˏ4-di-N-oxide substitutes at 7-position with esters group were synthetized and characterized by infrared (IR), proton nuclear magnetic resonance (1H-NMR), spectroscopy, and elemental analysis. Seventeen derivatives (M1-M3, E1-E8, P1-P3 and DR1-DR3) were selected and evaluated for antitumor activities using the NCI-60 human tumor cell lines screen. Results showed that E7, P3 and E6 were the most active compounds against the cell lines tested. Substitutions at 7-position with esters group not necessarily affect the biological activity, but the nature of the esters group could exert an influence on the selectivity. Additionally, substitutions at 2-position influenced the cytotoxic activity of the compounds. PMID:29201086
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The Mouse SAGE Site: database of public mouse SAGE libraries
Czech Academy of Sciences Publication Activity Database
Divina, Petr; Forejt, Jiří
2004-01-01
Roč. 32, - (2004), s. D482-D483 ISSN 0305-1048 R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015 Grant - others:HHMI(US) 555000306 Institutional research plan: CEZ:AV0Z5052915 Keywords : mouse SAGE libraries * web -based database Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.260, year: 2004
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Mouse manipulation through single-switch scanning.
Blackstien-Adler, Susie; Shein, Fraser; Quintal, Janet; Birch, Shae; Weiss, Patrice L Tamar
2004-01-01
Given the current extensive reliance on the graphical user interface, independent access to computer software requires that users be able to manipulate a pointing device of some type (e.g., mouse, trackball) or be able to emulate a mouse by some other means (e.g., scanning). The purpose of the present study was to identify one or more optimal single-switch scanning mouse emulation strategies. Four alternative scanning strategies (continuous Cartesian, discrete Cartesian, rotational, and hybrid quadrant/continuous Cartesian) were selected for testing based on current market availability as well as on theoretical considerations of their potential speed and accuracy. Each strategy was evaluated using a repeated measures study design by means of a test program that permitted mouse emulation via any one of four scanning strategies in a motivating environment; response speed and accuracy could be automatically recorded and considered in view of the motor, cognitive, and perceptual demands of each scanning strategy. Ten individuals whose disabilities required them to operate a computer via single-switch scanning participated in the study. Results indicated that Cartesian scanning was the preferred and most effective scanning strategy. There were no significant differences between results from the Continuous Cartesian and Discrete Cartesian scanning strategies. Rotational scanning was quite slow with respect to the other strategies, although it was equally accurate. Hybrid Quadrant scanning improved access time but at the cost of fewer correct selections. These results demonstrated the importance of testing and comparing alternate single-switch scanning strategies.
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Effect of potassium channel modulators in mouse forced swimming test
Galeotti, Nicoletta; Ghelardini, Carla; Caldari, Bernardetta; Bartolini, Alessandro
1999-01-01
The effect of intracerebroventricular (i.c.v.) administration of different potassium channel blockers (tetraethylammonium, apamin, charybdotoxin, gliquidone), potassium channel openers (pinacidil, minoxidil, cromakalim) and aODN to mKv1.1 on immobility time was evaluated in the mouse forced swimming test, an animal model of depression. Tetraethylammonium (TEA; 5 μg per mouse i.c.v.), apamin (3 ng per mouse i.c.v.), charybdotoxin (1 μg per mouse i.c.v.) and gliquidone (6 μg per mouse i.c.v.) administered 20 min before the test produced anti-immobility comparable to that induced by the tricyclic antidepressants amitriptyline (15 mg kg−1 s.c.) and imipramine (30 mg kg−1 s.c.). By contrast pinacidil (10–20 μg per mouse i.c.v.), minoxidil (10–20 μg per mouse i.c.v.) and cromakalim (20–30 μg per mouse i.c.v.) increased immobility time when administered in the same experimental conditions. Repeated administration of an antisense oligonucleotide (aODN) to the mKv1.1 gene (1 and 3 nmol per single i.c.v. injection) produced a dose-dependent increase in immobility time of mice 72 h after the last injection. At day 7, the increasing effect produced by aODN disappeared. A degenerate mKv1.1 oligonucleotide (dODN), used as control, did not produce any effect in comparison with saline- and vector-treated mice. At the highest effective dose, potassium channels modulators and the mKv1.1 aODN did not impair motor coordination, as revealed by the rota rod test, nor did they modify spontaneous motility as revealed by the Animex apparatus. These results suggest that modulation of potassium channels plays an important role in the regulation of immobility time in the mouse forced swimming test. PMID:10323599
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Chromosomal localization of the human and mouse hyaluronan synthase genes
Energy Technology Data Exchange (ETDEWEB)
Spicer, A.P.; McDonald, J.A. [Mayo Clinic Scottsdale, AZ (United States); Seldin, M.F. [Univ. of California Davis, CA (United States)] [and others
1997-05-01
We have recently identified a new vertebrate gene family encoding putative hyaluronan (HA) synthases. Three highly conserved related genes have been identified, designated HAS1, HAS2, and HAS3 in humans and Has1, Has2, and Has3 in the mouse. All three genes encode predicted plasma membrane proteins with multiple transmembrane domains and approximately 25% amino acid sequence identity to the Streptococcus pyogenes HA synthase, HasA. Furthermore, expression of any one HAS gene in transfected mammalian cells leads to high levels of HA biosynthesis. We now report the chromosomal localization of the three HAS genes in human and in mouse. The genes localized to three different positions within both the human and the mouse genomes. HAS1 was localized to the human chromosome 19q13.3-q13.4 boundary and Has1 to mouse Chr 17. HAS2 was localized to human chromosome 8q24.12 and Has2 to mouse Chr 15. HAS3 was localized to human chromosome 16q22.1 and Has3 to mouse Chr 8. The map position for HAS1 reinforces the recently reported relationship between a small region of human chromosome 19q and proximal mouse chromosome 17. HAS2 mapped outside the predicted critical region delineated for the Langer-Giedion syndrome and can thus be excluded as a candidate gene for this genetic syndrome. 33 refs., 2 figs.
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Comparison of three mouse strains by radiosensitivity of hemato-immune system
International Nuclear Information System (INIS)
Li, Deguan; Wu, Hongying; Wang, Yong; Zhang, Junling; Wang, Yueying; Lu, Lu; Meng, Aimin
2008-01-01
IRM-2, developed in our Lab, is an inbred strain mouse created by cross of a ICR/JCL female and 615 male mouse. Compared to the parent strains, the IRM-2 mouse exhibit increased resistance to radiation. We examine the damage of hemato-immune system induced by radiation in IRM-2, ICR and 615 mice in order to elucidate the radiation resistant mechanism of IRM-2 mouse. The hemato-immune function and radiosensitivities of three mouse strains (IRM-2, ICR/JCL, 615) have been compared using the following parameters: the white blood cells (WBC) in peripheral blood (PB), the bone marrow nucleated cells (BMC) per femur. Percent of phagocytosis of peritoneal macrophage (PM) was checked by chicken red blood cells. Lymphocyte phenotype in PB were analyzed by flow cytometry. Damage induced by radiation were analysed in the bone marrows cells, splenocytes and thymocyte exposed to irradiation in vitro by cell viability assay (ATP Bioluminescence assay) and apoptosis assay (Annexin V/PI). The WBC and BMC of IRM-2 mice were significantly higher than those in ICR mice and 615 mice, respectively (P<0.01). The ratio of CD4/CD8 in PB of IRM-2 mouse was lower than those in ICR and 615, P<0.01. Cell viability showed difference after 18 hs incubation post radiation in three mouse strains. The results of our primary study suggest that the hemato-immune function in IRM-2 mouse is different to its parent strains. The IRM-2 mouse provides an animal model to conducted further investigation to explore the role of hemato-immune system in radiation resistance. (author)
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Immunohistochemical visualization of mouse interneuron subtypes
DEFF Research Database (Denmark)
Jensen, Simon Mølgaard; Ulrichsen, Maj; Boggild, Simon
2014-01-01
, and calretinin are also commonly used as markers to narrow down the specific interneuron subtype. Here, we describe a journey to find the necessary immunological reagents for studying GABAergic interneurons of the mouse hippocampus. Based on web searches there are several hundreds of different antibodies...... of the hippocampus where they have previously been described. Additionally, the antibodies were also tested on sections from mouse spinal cord with similar criteria for specificity of the antibodies. Using the antibodies with a high rating on pAbmAbs, stainings with high signal-to-noise ratios and location...
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International Nuclear Information System (INIS)
Jain, N.; Bhatia, A.L.
1994-01-01
An evaluation of tritium toxicity in the developing mouse brain has demonstrated that the cerebellum is fairly vulnerable to tritium exposure even in young adult mice. Tritium toxicity in the postnatally developing mouse cerebellum with respect to the radiopathological changes has also been reported. In the absence of adequate dose response data on inhaled beta emitting radionuclides in man, it is necessary to obtain such information in experimental animals. This presentation is an attempt to look into the toxicity of tritium on the cerebellum of developing Swiss albino mice and hence, to collect such dose response data which are necessary to establish the safety standards for the personnel involved with radiation protection programs
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Energy Technology Data Exchange (ETDEWEB)
Du, Shisuo; Bouquet, Sophie; Lo, Chen-Hao; Pellicciotta, Ilenia; Bolourchi, Shiva [Department of Radiation Oncology, New York University School of Medicine, New York, New York (United States); Parry, Renate [Varian Medical Systems, Palo Alto, California (United States); Barcellos-Hoff, Mary Helen, E-mail: mhbarcellos-hoff@nyumc.org [Department of Radiation Oncology, New York University School of Medicine, New York, New York (United States)
2015-01-01
Purpose: To determine whether transforming growth factor (TGF)-β inhibition increases the response to radiation therapy in human and mouse non–small-cell lung carcinoma (NSCLC) cells in vitro and in vivo. Methods and Materials: TGF-β–mediated growth response and pathway activation were examined in human NSCLC NCI-H1299, NCI-H292, and A549 cell lines and murine Lewis lung cancer (LLC) cells. Cells were treated in vitro with LY364947, a small-molecule inhibitor of the TGF-β type 1 receptor kinase, or with the pan-isoform TGF-β neutralizing monoclonal antibody 1D11 before radiation exposure. The DNA damage response was assessed by ataxia telangiectasia mutated (ATM) or Trp53 protein phosphorylation, γH2AX foci formation, or comet assay in irradiated cells. Radiation sensitivity was determined by clonogenic assay. Mice bearing syngeneic subcutaneous LLC tumors were treated with 5 fractions of 6 Gy and/or neutralizing or control antibody. Results: The NCI-H1299, A549, and LLC NSCLC cell lines pretreated with LY364947 before radiation exposure exhibited compromised DNA damage response, indicated by decreased ATM and p53 phosphorylation, reduced γH2AX foci, and increased radiosensitivity. The NCI-H292 cells were unresponsive. Transforming growth factor-β signaling inhibition in irradiated LLC cells resulted in unresolved DNA damage. Subcutaneous LLC tumors in mice treated with TGF-β neutralizing antibody exhibited fewer γH2AX foci after irradiation and significantly greater tumor growth delay in combination with fractionated radiation. Conclusions: Inhibition of TGF-β before radiation attenuated DNA damage recognition and increased radiosensitivity in most NSCLC cells in vitro and promoted radiation-induced tumor control in vivo. These data support the rationale for concurrent TGF-β inhibition and RT to provide therapeutic benefit in NSCLC.
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A Humanized Mouse Model Generated Using Surplus Neonatal Tissue
Directory of Open Access Journals (Sweden)
Matthew E. Brown
2018-04-01
Full Text Available Summary: Here, we describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood hematopoietic stem cells (HSCs. Conventional humanized mouse models are made by engrafting human fetal thymus and HSCs into immunocompromised mice. These mice harbor functional human T cells that have matured in the presence of human self-peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more abundant and developmentally mature and allows for creation of up to ∼50-fold more mice per donor compared with fetal tissue models. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. The NeoThy model may provide significant advantages for induced pluripotent stem cell immunogenicity studies, while bypassing the requirement for fetal tissue. : Corresponding author William Burlingham and colleagues created a humanized mouse model called the NeoThy. The NeoThy uses human neonatal, rather than fetal, tissue sources for generating a human immune system within immunocompromised mouse hosts. NeoThy mice are an attractive alternative to conventional humanized mouse models, as they enable robust and reproducible iPSC immunogenicity experiments in vivo. Keywords: NeoThy, humanized mouse, iPSC, PSC, immunogenicity, transplantation, immunology, hematopoietic stem cells, induced pluripotent stem cells, thymus
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Astonishing advances in mouse genetic tools for biomedical research.
Kaczmarczyk, Lech; Jackson, Walker S
2015-01-01
The humble house mouse has long been a workhorse model system in biomedical research. The technology for introducing site-specific genome modifications led to Nobel Prizes for its pioneers and opened a new era of mouse genetics. However, this technology was very time-consuming and technically demanding. As a result, many investigators continued to employ easier genome manipulation methods, though resulting models can suffer from overlooked or underestimated consequences. Another breakthrough, invaluable for the molecular dissection of disease mechanisms, was the invention of high-throughput methods to measure the expression of a plethora of genes in parallel. However, the use of samples containing material from multiple cell types could obfuscate data, and thus interpretations. In this review we highlight some important issues in experimental approaches using mouse models for biomedical research. We then discuss recent technological advances in mouse genetics that are revolutionising human disease research. Mouse genomes are now easily manipulated at precise locations thanks to guided endonucleases, such as transcription activator-like effector nucleases (TALENs) or the CRISPR/Cas9 system, both also having the potential to turn the dream of human gene therapy into reality. Newly developed methods of cell type-specific isolation of transcriptomes from crude tissue homogenates, followed by detection with next generation sequencing (NGS), are vastly improving gene regulation studies. Taken together, these amazing tools simplify the creation of much more accurate mouse models of human disease, and enable the extraction of hitherto unobtainable data.
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Borth, N; Heider, R; Assadian, A; Katinger, H
1992-09-01
The growth and production kinetics of a mouse hybridoma cell line and a human-mouse heterohybridoma were analyzed under conditions of reduced temperature and serum content. The mouse hybridoma P24 had a constant cell specific production rate and RNA content, while the heterohybridoma 3D6-LC4 showed growth associated production kinetics and an increased RNA content at higher growth rates. This behaviour of 3D6-LC4 cells can be explained by the unusual cell cycle kinetics of this line, which can be arrested in any phase under growth limiting conditions, so that a low growth rate does not result in a greater portion of high producing G1-phase cells. Substrate limitation changes the cell cycle distribution of this cell line to a greater extent than low temperature or serum content, which indicates that this stress factor exerts a greater physiological control than assumed.
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Simple and efficient expression of codon-optimized mouse leukemia ...
African Journals Online (AJOL)
Purpose: To obtain a higher yield of mouse leukemia inhibitory factor to maintain the proliferation potential of pluripotent ... It induces mouse myeloid leukemic M1 cells of terminal ... induces the production of acute phase proteins by lipocyte ...
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Baillie-Johnson, Peter; van den Brink, Susanne Carina; Balayo, Tina; Turner, David Andrew; Martinez Arias, Alfonso
2015-11-24
We have developed a protocol improving current Embryoid Body (EB) culture which allows the study of self-organization, symmetry breaking, axial elongation and cell fate specification using aggregates of mouse embryonic stem cells (mESCs) in suspension culture. Small numbers of mESCs are aggregated in basal medium for 48 hr in non-tissue-culture-treated, U-bottomed 96-well plates, after which they are competent to respond to experimental signals. Following treatment, these aggregates begin to show signs of polarized gene expression and gradually alter their morphology from a spherical mass of cells to an elongated, well organized structure in the absence of external asymmetry cues. These structures are not only able to display markers of the three germ layers, but actively display gastrulation-like movements, evidenced by a directional dislodgement of individual cells from the aggregate, which crucially occurs at one region of the elongated structure. This protocol provides a detailed method for the reproducible formation of these aggregates, their stimulation with signals such as Wnt/β-Catenin activation and BMP inhibition and their analysis by single time-point or time-lapse fluorescent microscopy. In addition, we describe modifications to current whole-mount mouse embryo staining procedures for immunocytochemical analysis of specific markers within fixed aggregates. The changes in morphology, gene expression and length of the aggregates can be quantitatively measured, providing information on how signals can alter axial fates. It is envisaged that this system can be applied both to the study of early developmental events such as axial development and organization, and more broadly, the processes of self-organization and cellular decision-making. It may also provide a suitable niche for the generation of cell types present in the embryo that are unobtainable from conventional adherent culture such as spinal cord and motor neurones.
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International Nuclear Information System (INIS)
Anon.
1990-01-01
Data from seven studies sponsored by the National Cancer Institute (NCI) were used to determine current rates of breast cancer screening and to identify the characteristics of and reasons for women not being screened. All seven studies were population-based surveys of women aged 50 to 74 years without breast cancer. While over 90% of non-Hispanic white respondents had regular sources of medical care, 46% to 76% had a clinical breast examination within the previous year, and only 25% to 41% had a mammogram. Less educated and poorer women had fewer mammograms. The two most common reasons women gave for never having had a mammogram were that they did not known they needed it and that their physician had not recommended it. Many physicians may have overlooked the opportunity to recommend mammography for older women when performing a clinical breast examination and to educate their patients about the benefit of screening mammography
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An update on the mouse liver proteome
Directory of Open Access Journals (Sweden)
Borlak Jürgen
2009-09-01
Full Text Available Abstract Background Decoding of the liver proteome is subject of intense research, but hampered by methodological constraints. We recently developed an improved protocol for studying rat liver proteins based on 2-DE-MALDI-TOF-MS peptide mass finger printing. This methodology was now applied to develop a mouse liver protein database. Results Liver proteins were extracted by two different lysis buffers in sequence followed by a liquid-phase IEF pre-fractionation and separation of proteins by 2 DE at two different pH ranges, notably 5-8 and 7-10. Based on 9600 in gel digests a total of 643 mouse liver proteins with high sequence coverage (> 20 peptides per protein could be identified by MALDI-TOF-MS peptide mass finger printing. Notably, 255 proteins are novel and have not been reported so far by conventional two-dimensional electrophoresis proteome mapping. Additionally, the results of the present findings for mouse liver were compared to published data of the rat proteome to compile as many proteins as possible in a rodent liver database. Conclusion Based on 2-DE MALDI-TOF-MS a significantly improved proteome map of mouse liver was obtained. We discuss some prominent members of newly identified proteins for a better understanding of liver biology.
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Directory of Open Access Journals (Sweden)
Searle Jeremy B
2010-10-01
Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325
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Characteristics of the mouse genomic histamine H1 receptor gene
Energy Technology Data Exchange (ETDEWEB)
Inoue, Isao; Taniuchi, Ichiro; Kitamura, Daisuke [Kyushu Univ., Fukuoka (Japan)] [and others
1996-08-15
We report here the molecular cloning of a mouse histamine H1 receptor gene. The protein deduced from the nucleotide sequence is composed of 488 amino acid residues with characteristic properties of GTP binding protein-coupled receptors. Our results suggest that the mouse histamine H1 receptor gene is a single locus, and no related sequences were detected. Interspecific backcross analysis indicated that the mouse histamine H1 receptor gene (Hrh1) is located in the central region of mouse Chromosome 6 linked to microphthalmia (Mitfmi), ras-related fibrosarcoma oncogene 1 (Raf1), and ret proto-oncogene (Ret) in a region of homology with human chromosome 3p. 12 refs., 3 figs.
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The Mouse House: A brief history of the ORNL mouse-genetics program, 1947–2009
Energy Technology Data Exchange (ETDEWEB)
Russell, Liane B.
2013-10-01
The large mouse genetics program at the Oak Ridge National Lab is often re-membered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-Chromosome s importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a valuable
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Testing parasite 'intimacy': the whipworm Trichuris muris in the European house mouse hybrid zone.
Wasimuddin; Bryja, Josef; Ribas, Alexis; Baird, Stuart J E; Piálek, Jaroslav; Goüy de Bellocq, Joëlle
2016-05-01
Host-parasite interaction studies across hybrid zones often focus on host genetic variation, treating parasites as homogeneous. 'Intimately' associated hosts and parasites might be expected to show similar patterns of genetic structure. In the literature, factors such as no intermediate host and no free-living stage have been proposed as 'intimacy' factors likely constraining parasites to closely follow the evolutionary history of their hosts. To test whether the whipworm, Trichuris muris, is intimately associated with its house mouse host, we studied its population genetics across the European house mouse hybrid zone (HMHZ) which has a strong central barrier to gene flow between mouse taxa. T. muris has a direct life cycle and nonmobile free stage: if these traits constrain the parasite to an intimate association with its host we expect a geographic break in the parasite genetic structure across the HMHZ. We genotyped 205 worms from 56 localities across the HMHZ and additionally T. muris collected from sympatric woodmice (Apodemus spp.) and allopatric murine species, using mt-COX1, ITS1-5.8S-ITS2 rDNA and 10 microsatellites. We show four haplogroups of mt-COX1 and three clear ITS1-5.8S-ITS2 clades in the HMHZ suggesting a complex demographic/phylogeographic history. Microsatellites show strong structure between groups of localities. However, no marker type shows a break across the HMHZ. Whipworms from Apodemus in the HMHZ cluster, and share mitochondrial haplotypes, with those from house mice. We conclude Trichuris should not be regarded as an 'intimate' parasite of the house mouse: while its life history might suggest intimacy, passage through alternate hosts is sufficiently common to erase signal of genetic structure associated with any particular host taxon.
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Zhu, Xin-Hua; Liao, Bing; Xu, Yi; Liu, Ke; Huang, Yun; Huang, Quan-Long; Liu, Yue-Hui
2017-02-01
RNA interference has been considered as an effective gene silencing method in basic and preclinical investigations. The aims of the present study were to construct a lentiviral vector expressing a short hairpin RNA (shRNA) targeting the murine CC chemokine receptor 3 (mCCR3), and to investigate its effects on the proliferation and apoptosis of mouse eosinophils. A recombinant lentiviral vector expressing four fragments of mouse CCR3 shRNA (pLVX‑mCCR3‑1+2+3+4‑shRNA) was constructed using subcloning techniques. This novel lentivirus was then packaged into 293T cells by co‑transduction with plasmids, including Baculo p35, pCMV R8.2 and VSV. The interference effects of the vector were verified using polymerase chain reaction (PCR) and western blot analyses. The effects of the interference on the proliferation and apoptosis of mouse eosinophils were investigated using 3‑(4,5‑dimethylthiazol‑2‑yl)‑5‑(3‑carboxymethoxyphenyl)‑2‑(4‑sulfophenyl)‑2H‑tetrazolium and terminal deoxynucleotidyl transferase dUTP nick end labeling methods, respectively. The results of the PCR and western blot analyses confirmed that the novel recombinant vector, pLVX‑mCCR3‑1+2+3+4‑shRNA, had high efficiency in inhibiting the mRNA and protein expression levels of mCCR3 in mouse eosinophils. The downregulation of mCCR3 significantly inhibited proliferation of the eosinophils. Furthermore, the present study found that the downregulation of mCCR3 significantly promoted apoptosis of the eosinophils. Therefore, the downregulation of mCCR3 led to the inhibition of proliferation and induction of apoptosis in mouse eosinophils. The predominant characteristics of allergic rhinitis are eosinophil infiltration and release of inflammatory mediators, which appear in a variety of clinical manifestations. The results of the present study indicate that mCCR3 silencing may serve as a putative approach for the treatment of allergic rhinitis.
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Zhu, Jinmin; Fan, Fangfang; McCarthy, Deirdre M; Zhang, Lin; Cannon, Elisa N; Spencer, Thomas J; Biederman, Joseph; Bhide, Pradeep G
2017-05-01
Prenatal exposure to nicotine via cigarette smoke or other forms of tobacco use is a significant environmental risk factor for attention deficit hyperactivity disorder (ADHD). The neurobiological mechanisms underlying the link between prenatal nicotine exposure (PNE) and ADHD are not well understood. Animal models, especially rodent models, are beginning to bridge this gap in knowledge. Although ADHD is characterized by hyperactivity, inattention, impulsivity and working memory deficits, the majority of the animal models are based on only one or two ADHD associated phenotypes, in particular, hyperactivity or inattention. We report a PNE mouse model that displays the full range of ADHD associated behavioral phenotypes including working memory deficit, attention deficit and impulsive-like behavior. All of the ADHD-associated phenotypes respond to a single administration of a therapeutic equivalent dose of methylphenidate. In an earlier study, we showed that PNE produces hyperactivity, frontal cortical hypodopaminergic state and thinning of the cingulate cortex. Collectively, these data suggest that the PNE mouse model recapitulates key features of ADHD and may be a suitable preclinical model for ADHD research. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.
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Suppression of mouse-killing in rats following irradiation
International Nuclear Information System (INIS)
O'Boyle, M.
1976-01-01
Suppression of mouse-killing was produced following pairings of mouse-presentations (CS) with 96 roentgens of ionizing radiation (US) at 0 (less than 2 min.) and 30 min. US-CS interstimulus intervals. No suppression was found at CS-US intervals of 30 min., 1 hr., and 2 hr., or at US-CS intervals of 1 hr. and 2 hr
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HOCOMOCO: expansion and enhancement of the collection of transcription factor binding sites models
Kulakovskiy, Ivan V.
2015-11-19
Models of transcription factor (TF) binding sites provide a basis for a wide spectrum of studies in regulatory genomics, from reconstruction of regulatory networks to functional annotation of transcripts and sequence variants. While TFs may recognize different sequence patterns in different conditions, it is pragmatic to have a single generic model for each particular TF as a baseline for practical applications. Here we present the expanded and enhanced version of HOCOMOCO (http://hocomoco.autosome.ru and http://www.cbrc.kaust.edu.sa/hocomoco10), the collection of models of DNA patterns, recognized by transcription factors. HOCOMOCO now provides position weight matrix (PWM) models for binding sites of 601 human TFs and, in addition, PWMs for 396 mouse TFs. Furthermore, we introduce the largest up to date collection of dinucleotide PWM models for 86 (52) human (mouse) TFs. The update is based on the analysis of massive ChIP-Seq and HT-SELEX datasets, with the validation of the resulting models on in vivo data. To facilitate a practical application, all HOCOMOCO models are linked to gene and protein databases (Entrez Gene, HGNC, UniProt) and accompanied by precomputed score thresholds. Finally, we provide command-line tools for PWM and diPWM threshold estimation and motif finding in nucleotide sequences.
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Gene expression and functional annotation of the human and mouse choroid plexus epithelium.
Directory of Open Access Journals (Sweden)
Sarah F Janssen
Full Text Available BACKGROUND: The choroid plexus epithelium (CPE is a lobed neuro-epithelial structure that forms the outer blood-brain barrier. The CPE protrudes into the brain ventricles and produces the cerebrospinal fluid (CSF, which is crucial for brain homeostasis. Malfunction of the CPE is possibly implicated in disorders like Alzheimer disease, hydrocephalus or glaucoma. To study human genetic diseases and potential new therapies, mouse models are widely used. This requires a detailed knowledge of similarities and differences in gene expression and functional annotation between the species. The aim of this study is to analyze and compare gene expression and functional annotation of healthy human and mouse CPE. METHODS: We performed 44k Agilent microarray hybridizations with RNA derived from laser dissected healthy human and mouse CPE cells. We functionally annotated and compared the gene expression data of human and mouse CPE using the knowledge database Ingenuity. We searched for common and species specific gene expression patterns and function between human and mouse CPE. We also made a comparison with previously published CPE human and mouse gene expression data. RESULTS: Overall, the human and mouse CPE transcriptomes are very similar. Their major functionalities included epithelial junctions, transport, energy production, neuro-endocrine signaling, as well as immunological, neurological and hematological functions and disorders. The mouse CPE presented two additional functions not found in the human CPE: carbohydrate metabolism and a more extensive list of (neural developmental functions. We found three genes specifically expressed in the mouse CPE compared to human CPE, being ACE, PON1 and TRIM3 and no human specifically expressed CPE genes compared to mouse CPE. CONCLUSION: Human and mouse CPE transcriptomes are very similar, and display many common functionalities. Nonetheless, we also identified a few genes and pathways which suggest that the CPE
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Stanley, Joanna L; Lincoln, Rachael J; Brown, Terry A; McDonald, Louise M; Dawson, Gerard R; Reynolds, David S
2005-05-01
The mouse rotarod test of motor coordination/sedation is commonly used to predict clinical sedation caused by novel drugs. However, past experience suggests that it lacks the desired degree of sensitivity to be predictive of effects in humans. For example, the benzodiazepine, bretazenil, showed little impairment of mouse rotarod performance, but marked sedation in humans. The aim of the present study was to assess whether the mouse beam walking assay demonstrates: (i) an increased sensitivity over the rotarod and (ii) an increased ability to predict clinically sedative doses of benzodiazepines. The study compared the effects of the full benzodiazepine agonists, diazepam and lorazepam, and the partial agonist, bretazenil, on the mouse rotarod and beam walking assays. Diazepam and lorazepam significantly impaired rotarod performance, although relatively high GABA-A receptor occupancy was required (72% and 93%, respectively), whereas beam walking performance was significantly affected at approximately 30% receptor occupancy. Bretazenil produced significant deficits at 90% and 53% receptor occupancy on the rotarod and beam walking assays, respectively. The results suggest that the mouse beam walking assay is a more sensitive tool for determining benzodiazepine-induced motor coordination deficits than the rotarod. Furthermore, the GABA-A receptor occupancy values at which significant deficits were determined in the beam walking assay are comparable with those observed in clinical positron emission tomography studies using sedative doses of benzodiazepines. These data suggest that the beam walking assay may be able to more accurately predict the clinically sedative doses of novel benzodiazepine-like drugs.
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Enhancement of mouse sperm motility by trophinin-binding peptide
Directory of Open Access Journals (Sweden)
Park Seong
2012-11-01
Full Text Available Abstract Background Trophinin is an intrinsic membrane protein that forms a complex in the cytoplasm with bystin and tastin, linking it microtubule-associated motor dynein (ATPase in some cell types. Previously, we found that human sperm tails contain trophinin, bystin and tastin proteins, and that trophinin-binding GWRQ (glycine, tryptophan, arginine, glutamine peptide enhanced motility of human sperm. Methods Immunohistochemistry was employed to determine trophinin protein in mouse spermatozoa from wild type mouse, by using spermatozoa from trophinin null mutant mice as a negative control. Multivalent 8-branched GWRQ (glycine, tryptophan, arginine, glutamine peptide or GWRQ-MAPS, was chemically synthesized, purified by HPLC and its structure was confirmed by MALDI-TOF mass spectrometry. Effect of GWRQ-MAPS on mouse spermatozoa from wild type and trophinin null mutant was assessed by a computer-assisted semen analyzer (CASA. Results Anti-trophinin antibody stained the principal (central piece of the tail of wild type mouse sperm, whereas the antibody showed no staining on trophinin null sperm. Phage particles displaying GWRQ bound to the principal piece of sperm tail from wild type but not trophinin null mice. GWRQ-MAPS enhanced motility of spermatozoa from wild type but not trophinin null mice. CASA showed that GWRQ-MAPS enhanced both progressive motility and rapid motility in wild type mouse sperm. Conclusions Present study established the expression of trophinin in the mouse sperm tail and trophinin-dependent effect of GWRQ-MAPS on sperm motility. GWRQ causes a significant increase in sperm motility.
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Mouse ATP-Binding Cassette (ABC) Transporters Conferring Multi-Drug Resistance
Shuaizhang, L I; Zhang, Wen; Yin, Xuejiao; Xing, Shilai; Xie, Qunhui; Cao, Zhengyu; Zhao, Bin
2015-04-28
The ABC (ATP-binding cassette) transporter is one of the largest and most ancient protein families with members functioning from protozoa to human. The resistance of cancer and tumor cells to anticancer drugs is due to the over-expression of some ABC transporters, which may finally lead to chemotherapy failure. The mouse ABC transporters are classified into seven subfamilies by phylogenetic analysis. The mouse ABC transporter gene, alias, chromosomal location and function have been determined. Within the ABC super-family, the MDR transporters (Abcb1, Abcc1, Abcg2) in mouse models have been proved to be valuable to investigate the biochemistry and physiological functions. This review concentrates on the multidrug resistance of mouse ABC transporters in cancer and tumor cells.
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DEFF Research Database (Denmark)
Harbo, Anders La-Cour; Stoustrup, Jakob
2000-01-01
The infra red 3D mouse is a three dimensional input device to a computer. It works by determining the position of an arbitrary object (like a hand) by emitting infra red signals from a number of locations and measuring the reflected intensities. To maximize stability, robustness, and use of bandw......The infra red 3D mouse is a three dimensional input device to a computer. It works by determining the position of an arbitrary object (like a hand) by emitting infra red signals from a number of locations and measuring the reflected intensities. To maximize stability, robustness, and use...
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High-throughput mouse genotyping using robotics automation.
Linask, Kaari L; Lo, Cecilia W
2005-02-01
The use of mouse models is rapidly expanding in biomedical research. This has dictated the need for the rapid genotyping of mutant mouse colonies for more efficient utilization of animal holding space. We have established a high-throughput protocol for mouse genotyping using two robotics workstations: a liquid-handling robot to assemble PCR and a microfluidics electrophoresis robot for PCR product analysis. This dual-robotics setup incurs lower start-up costs than a fully automated system while still minimizing human intervention. Essential to this automation scheme is the construction of a database containing customized scripts for programming the robotics workstations. Using these scripts and the robotics systems, multiple combinations of genotyping reactions can be assembled simultaneously, allowing even complex genotyping data to be generated rapidly with consistency and accuracy. A detailed protocol, database, scripts, and additional background information are available at http://dir.nhlbi.nih.gov/labs/ldb-chd/autogene/.
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Providing training enhances the biomechanical improvements of an alternative computer mouse design
Houwink, A.; Oude Hengel, K.M.; Odell, D.; Dennerlein, J.T.
2009-01-01
To determine if an alternative mouse promotes more neutral postures and decreases forearm muscle activity and if training enhances these biomechanical benefits is the purpose of the study. Computer mouse use is a risk factor for developing musculoskeletal disorders; alternative mouse designs can
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Mouse Vocal Communication System: Are Ultrasounds Learned or Innate?
Arriaga, Gustavo; Jarvis, Erich D.
2013-01-01
Mouse ultrasonic vocalizations (USVs) are often used as behavioral readouts of internal states, to measure effects of social and pharmacological manipulations, and for behavioral phenotyping of mouse models for neuropsychiatric and neurodegenerative disorders. However, little is known about the neurobiological mechanisms of rodent USV production.…
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Tamoxifen-independent recombination in the RIP-CreER mouse.
Directory of Open Access Journals (Sweden)
Yanmei Liu
Full Text Available BACKGROUND: The inducible Cre-lox system is a valuable tool to study gene function in a spatial and time restricted fashion in mouse models. This strategy relies on the limited background activity of the modified Cre recombinase (CreER in the absence of its inducer, the competitive estrogen receptor ligand, tamoxifen. The RIP-CreER mouse (Tg (Ins2-cre/Esr1 1Dam is among the few available β-cell specific CreER mouse lines and thus it has been often used to manipulate gene expression in the insulin-producing cells of the endocrine pancreas. PRINCIPAL FINDINGS: Here, we report the detection of tamoxifen-independent Cre activity as early as 2 months of age in RIP-CreER mice crossed with three distinct reporter strains. SIGNIFICANCE: Evidence of Cre-mediated recombination of floxed alleles even in the absence of tamoxifen administration should warrant cautious use of this mouse for the study of pancreatic β-cells.
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A Mouse Model of Chronic West Nile Virus Disease.
Directory of Open Access Journals (Sweden)
Jessica B Graham
2016-11-01
Full Text Available Infection with West Nile virus (WNV leads to a range of disease outcomes, including chronic infection, though lack of a robust mouse model of chronic WNV infection has precluded identification of the immune events contributing to persistent infection. Using the Collaborative Cross, a population of recombinant inbred mouse strains with high levels of standing genetic variation, we have identified a mouse model of persistent WNV disease, with persistence of viral loads within the brain. Compared to lines exhibiting no disease or marked disease, the F1 cross CC(032x013F1 displays a strong immunoregulatory signature upon infection that correlates with restraint of the WNV-directed cytolytic response. We hypothesize that this regulatory T cell response sufficiently restrains the immune response such that a chronic infection can be maintained in the CNS. Use of this new mouse model of chronic neuroinvasive virus will be critical in developing improved strategies to prevent prolonged disease in humans.
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Perancangan Aplikasi Pengenal Alat Musik Tradisional Gandara Menggunakan Multipoint Mouse SDK
Directory of Open Access Journals (Sweden)
Arena Bayu Chandra Permana
2014-11-01
Full Text Available Young men nowadays have few interest with traditional art, including many kinds of Indonesia musical instruments. Compared with that traditional art, people are more familiar with multimedia application in computer devices. Based on those things, there is an idea to create a computer application to make famous Indonesia musical instruments by giving explanation and make a simulation. The application’s name is “Gandara”, a word from sanskrit language that means notes collection. “Gandara” uses MultiPoint Mouse SDK that makes the application to be able played by multiple users. The application is developed using Multimedia Development Life Cycle (MDLC that consist of concept, design, material collecting, assembly, testing and distribution. “Gandara” users can learn both of gamelan and angklung by reading the explanation or playing the simulation. With this applicaton, users don’t need to face gamelan and angklung directly when they want to exercise. All of “Gandara” functions can work well when tested with black-box method and got positif results when tested by users.
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4D atlas of the mouse embryo for precise morphological staging.
Wong, Michael D; van Eede, Matthijs C; Spring, Shoshana; Jevtic, Stefan; Boughner, Julia C; Lerch, Jason P; Henkelman, R Mark
2015-10-15
After more than a century of research, the mouse remains the gold-standard model system, for it recapitulates human development and disease and is quickly and highly tractable to genetic manipulations. Fundamental to the power and success of using a mouse model is the ability to stage embryonic mouse development accurately. Past staging systems were limited by the technologies of the day, such that only surface features, visible with a light microscope, could be recognized and used to define stages. With the advent of high-throughput 3D imaging tools that capture embryo morphology in microscopic detail, we now present the first 4D atlas staging system for mouse embryonic development using optical projection tomography and image registration methods. By tracking 3D trajectories of every anatomical point in the mouse embryo from E11.5 to E14.0, we established the first 4D atlas compiled from ex vivo 3D mouse embryo reference images. The resulting 4D atlas comprises 51 interpolated 3D images in this gestational range, resulting in a temporal resolution of 72 min. From this 4D atlas, any mouse embryo image can be subsequently compared and staged at the global, voxel and/or structural level. Assigning an embryonic stage to each point in anatomy allows for unprecedented quantitative analysis of developmental asynchrony among different anatomical structures in the same mouse embryo. This comprehensive developmental data set offers developmental biologists a new, powerful staging system that can identify and compare differences in developmental timing in wild-type embryos and shows promise for localizing deviations in mutant development. © 2015. Published by The Company of Biologists Ltd.
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Spatiotemporal expression of caveolin-1 and EMMPRIN during mouse tooth development.
Shi, Lu; Li, Lingyun; Wang, Ding; Li, Shu; Chen, Zhi; An, Zhengwen
2016-06-01
Caveolin-1 is a scaffolding protein involved in the formation of cholesterol-rich caveolae lipid rafts within the plasma membrane and is capable of collecting signaling molecules into the caveolae and regulating their activity, including extracellular matrix metalloproteinase inducer (EMMPRIN). However, detailed expression patterns of caveolin-1 and EMMPRIN in the developing dental germ are largely unknown. The present study investigated the expression patterns of caveolin-1 and EMMPRIN in the developing mouse tooth germ by immunohistochemistry and real-time polymerase chain reaction. At the bud stage, caveolin-1 expression was initiated in the epithelium bud and mesenchymal cells, while EMMPRIN was weakly expressed at this stage. At the cap stage, caveolin-1 protein was located in the lingual part of the tooth germ; however, EMMPRIN protein was located in the labial part. From the bell stage to 2 days postnatal, caveolin-1 expression was detected in the ameloblasts and cervical loop area; with EMMPRIN expression in the ameloblasts and odontoblasts. Real-time polymerase chain reaction results showed that both caveolin-1 and EMMPRIN mRNA levels increased gradually with progression of developmental stages, and peaked at day two postnatal. The current finding suggests that both caveolin-1 and EMMPRIN take part in mouse tooth development, especially in the differentiation and organization of odontogenic tissues.
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Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein.
Directory of Open Access Journals (Sweden)
Christian Much
2016-06-01
Full Text Available Dicer is a large multi-domain protein responsible for the ultimate step of microRNA and short-interfering RNA biogenesis. In human and mouse cell lines, Dicer has been shown to be important in the nuclear clearance of dsRNA as well as the establishment of chromatin modifications. Here we set out to unambiguously define the cellular localization of Dicer in mice to understand if this is a conserved feature of mammalian Dicer in vivo. To this end, we utilized an endogenously epitope tagged Dicer knock-in mouse allele. From primary mouse cell lines and adult tissues, we determined with certainty by biochemical fractionation and confocal immunofluorescence microscopy that endogenous Dicer is exclusively cytoplasmic. We ruled out the possibility that a fraction of Dicer shuttles to and from the nucleus as well as that FGF or DNA damage signaling induce Dicer nuclear translocation. We also explored Dicer localization during the dynamic and developmental context of embryogenesis, where Dicer is ubiquitously expressed and strictly cytoplasmic in all three germ layers as well as extraembryonic tissues. Our data exclude a direct role for Dicer in the nuclear RNA processing in the mouse.
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Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein.
Much, Christian; Auchynnikava, Tania; Pavlinic, Dinko; Buness, Andreas; Rappsilber, Juri; Benes, Vladimir; Allshire, Robin; O'Carroll, Dónal
2016-06-01
Dicer is a large multi-domain protein responsible for the ultimate step of microRNA and short-interfering RNA biogenesis. In human and mouse cell lines, Dicer has been shown to be important in the nuclear clearance of dsRNA as well as the establishment of chromatin modifications. Here we set out to unambiguously define the cellular localization of Dicer in mice to understand if this is a conserved feature of mammalian Dicer in vivo. To this end, we utilized an endogenously epitope tagged Dicer knock-in mouse allele. From primary mouse cell lines and adult tissues, we determined with certainty by biochemical fractionation and confocal immunofluorescence microscopy that endogenous Dicer is exclusively cytoplasmic. We ruled out the possibility that a fraction of Dicer shuttles to and from the nucleus as well as that FGF or DNA damage signaling induce Dicer nuclear translocation. We also explored Dicer localization during the dynamic and developmental context of embryogenesis, where Dicer is ubiquitously expressed and strictly cytoplasmic in all three germ layers as well as extraembryonic tissues. Our data exclude a direct role for Dicer in the nuclear RNA processing in the mouse.
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Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes
Rowley, Jesse W.; Oler, Andrew J.; Tolley, Neal D.; Hunter, Benjamin N.; Low, Elizabeth N.; Nix, David A.; Yost, Christian C.; Zimmerman, Guy A.
2011-01-01
Inbred mice are a useful tool for studying the in vivo functions of platelets. Nonetheless, the mRNA signature of mouse platelets is not known. Here, we use paired-end next-generation RNA sequencing (RNA-seq) to characterize the polyadenylated transcriptomes of human and mouse platelets. We report that RNA-seq provides unprecedented resolution of mRNAs that are expressed across the entire human and mouse genomes. Transcript expression and abundance are often conserved between the 2 species. Several mRNAs, however, are differentially expressed in human and mouse platelets. Moreover, previously described functional disparities between mouse and human platelets are reflected in differences at the transcript level, including protease activated receptor-1, protease activated receptor-3, platelet activating factor receptor, and factor V. This suggests that RNA-seq is a useful tool for predicting differences in platelet function between mice and humans. Our next-generation sequencing analysis provides new insights into the human and murine platelet transcriptomes. The sequencing dataset will be useful in the design of mouse models of hemostasis and a catalyst for discovery of new functions of platelets. Access to the dataset is found in the “Introduction.” PMID:21596849
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Dissection of the Mouse Pancreas for Histological Analysis and Metabolic Profiling.
Veite-Schmahl, Michelle J; Regan, Daniel P; Rivers, Adam C; Nowatzke, Joseph F; Kennedy, Michael A
2017-08-19
We have been investigating the pancreas specific transcription factor, 1a cre-recombinase; lox-stop-lox- Kristen rat sarcoma, glycine to aspartic acid at the 12 codon (Ptf1a cre/+ ;LSL-Kras G12D/+ ) mouse strain as a model of human pancreatic cancer. The goal of our current studies is to identify novel metabolic biomarkers of pancreatic cancer progression. We have performed metabolic profiling of urine, feces, blood, and pancreas tissue extracts, as well as histological analyses of the pancreas to stage the cancer progression. The mouse pancreas is not a well-defined solid organ like in humans, but rather is a diffusely distributed soft tissue that is not easily identified by individuals unfamiliar with mouse internal anatomy or by individuals that have little or no experience performing mouse organ dissections. The purpose of this article is to provide a detailed step-wise visual demonstration to guide novices in the removal of the mouse pancreas by dissection. This article should be especially valuable to students and investigators new to research that requires harvesting of the mouse pancreas by dissection for metabolic profiling or histological analyses.
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Using the mouse to model human disease: increasing validity and reproducibility
Directory of Open Access Journals (Sweden)
Monica J. Justice
2016-02-01
Full Text Available Experiments that use the mouse as a model for disease have recently come under scrutiny because of the repeated failure of data, particularly derived from preclinical studies, to be replicated or translated to humans. The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research. Inaccurate and incomplete descriptions of experimental conditions also contribute. Here, we provide guidance on best practice in mouse experimentation, focusing on appropriate selection and validation of the model, sources of variation and their influence on phenotypic outcomes, minimum requirements for control sets, and the importance of rigorous statistics. Our goal is to raise the standards in mouse disease modeling to enhance reproducibility, reliability and clinical translation of findings.
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Who Needs Statistics? | Poster
You may know the feeling. You have collected a lot of new data on an important experiment. Now you are faced with multiple groups of data, a sea of numbers, and a deadline for submitting your paper to a peer-reviewed journal. And you are not sure which data are relevant, or even the best way to present them. The statisticians at Data Management Services (DMS) know how to help. This small group of experts provides a wide array of statistical and mathematical consulting services to the scientific community at NCI at Frederick and NCI-Bethesda.
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An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man
Ravasi, Timothy; Suzuki, Harukazu; Cannistraci, Carlo; Katayama, Shintaro; Bajic, Vladimir B.; Tan, Kai; Akalin, Altuna; Schmeier, Sebastian; Kanamori-Katayama, Mutsumi; Bertin, Nicolas; Carninci, Piero; Daub, Carsten O.; Forrest, Alistair R.R.; Gough, Julian; Grimmond, Sean; Han, Jung-Hoon; Hashimoto, Takehiro; Hide, Winston; Hofmann, Oliver; Kamburov, Atanas; Kaur, Mandeep; Kawaji, Hideya; Kubosaki, Atsutaka; Lassmann, Timo; van Nimwegen, Erik; MacPherson, Cameron Ross; Ogawa, Chihiro; Radovanovic, Aleksandar; Schwartz, Ariel; Teasdale, Rohan D.; Tegné r, Jesper; Lenhard, Boris; Teichmann, Sarah A.; Arakawa, Takahiro; Ninomiya, Noriko; Murakami, Kayoko; Tagami, Michihira; Fukuda, Shiro; Imamura, Kengo; Kai, Chikatoshi; Ishihara, Ryoko; Kitazume, Yayoi; Kawai, Jun; Hume, David A.; Ideker, Trey; Hayashizaki, Yoshihide
2010-01-01
Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.
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An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man
Ravasi, Timothy
2010-03-01
Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.
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Mouse tetranectin: cDNA sequence, tissue-specific expression, and chromosomal mapping
DEFF Research Database (Denmark)
Ibaraki, K; Kozak, C A; Wewer, U M
1995-01-01
regulation, mouse tetranectin cDNA was cloned from a 16-day-old mouse embryo library. Sequence analysis revealed a 992-bp cDNA with an open reading frame of 606 bp, which is identical in length to the human tetranectin cDNA. The deduced amino acid sequence showed high homology to the human cDNA with 76......(s) of tetranectin. The sequence analysis revealed a difference in both sequence and size of the noncoding regions between mouse and human cDNAs. Northern analysis of the various tissues from mouse, rat, and cow showed the major transcript(s) to be approximately 1 kb, which is similar in size to that observed...
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International Nuclear Information System (INIS)
Denis, Fabrice; Garaud, Pascal; Bardet, Etienne; Alfonsi, Marc; Sire, Christian; Germain, Thierry; Bergerot, Philippe; Rhein, Beatrix; Tortochaux, Jacques; Oudinot, Patrick; Calais, Gilles
2003-01-01
Purpose: To prospectively assess 5-year late toxicity in patients treated by concomitant radiochemotherapy for locally advanced oropharynx carcinoma using three different toxicity scales. Methods and Materials: A total of 226 patients were entered in a Phase III multicenter, randomized trial comparing radiotherapy alone (70 Gy in 35 fractions: Arm A) with concomitant radiochemotherapy (70 Gy in 35 fractions with three cycles of a 4-day regimen containing carboplatin and 5-fluorouracil: Arm B). Five living patients, free of local or distant recurrences, could not be evaluated for late toxicity. Forty-four patients were eligible for late toxicity with a median follow-up of 5 years. Late toxicity was evaluated by the radiation oncologist using a large questionnaire containing 120 mixed items of three scales (NCI-CTC, LENT/SOMA, and RTOG). The data were then transposed on separate scales using corresponding grades. Results: The 5-year overall survival rate was 22% in Arm B and 16% in Arm A (p=0.05). The 5-year locoregional control rate was 48% in Arm B and 25% in Arm A (p=0.002). The spinal cord was not affected by the concomitant adjunct of chemotherapy, and no deaths were caused by late toxicity. Using the three late toxicity scales, 100% of the patients treated with the combined modality (Arm B) developed one or more late complications vs. 94% in the radiotherapy-alone arm (Arm A). The difference was not statistically significant. The most commonly damaged organs (all Grade 1-4) were the salivary glands (100% in Arm B vs. 82% in Arm A, p<0.05), skin (78% vs. 47%, p<0.05), teeth (67% vs. 18%, p<0.05), mucosa (59% vs. 63% p = not significant), and mandible (44% vs. 12%, p<0.05). One or more Grade 3-4 complications occurred in 82% of the patients in Arm B vs. 47% in Arm A (p=0.02) but concerned only the teeth. The correlation between the RTOG and LENT/SOMA scale and between the NCI-CTC and LENT/SOMA scale were low for Grade 1-4 toxicity (near 30%). The transposability
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Directory of Open Access Journals (Sweden)
Jasmine eGrimsley
2013-01-01
Full Text Available Mouse pups vocalize at high rates when they are cold or isolated from the nest. The proportions of each syllable type produced carry information about disease state and are being used as behavioral markers for the internal state of animals. Manual classifications of these vocalizations identified ten syllable types based on their spectro-temporal features. However, manual classification of mouse syllables is time consuming and vulnerable to experimenter bias. This study uses an automated cluster analysis to identify acoustically distinct syllable types produced by CBA/CaJ mouse pups, and then compares the results to prior manual classification methods. The cluster analysis identified two syllable types, based on their frequency bands, that have continuous frequency-time structure, and two syllable types featuring abrupt frequency transitions. Although cluster analysis computed fewer syllable types than manual classification, the clusters represented well the probability distributions of the acoustic features within syllables. These probability distributions indicate that some of the manually classified syllable types are not statistically distinct. The characteristics of the four classified clusters were used to generate a Microsoft Excel-based mouse syllable classifier that rapidly categorizes syllables, with over a 90% match, into the syllable types determined by cluster analysis.
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Sex-reversed somatic cell cloning in the mouse.
Inoue, Kimiko; Ogonuki, Narumi; Mekada, Kazuyuki; Yoshiki, Atsushi; Sado, Takashi; Ogura, Atsuo
2009-10-01
Somatic cell nuclear transfer has many potential applications in the fields of basic and applied sciences. However, it has a disadvantage that can never be overcome technically-the inflexibility of the sex of the offspring. Here, we report an accidental birth of a female mouse following nuclear transfer using an immature Sertoli cell. We produced a batch of 27 clones in a nuclear transfer experiment using Sertoli cells collected from neonatal male mice. Among them, one pup was female. This "male-derived female" clone grew into a normal adult and produced offspring by natural mating with a littermate. Chromosomal analysis revealed that the female clone had a 39,X karyotype, indicating that the Y chromosome had been deleted in the donor cell or at some early step during nuclear transfer. This finding suggests the possibility of resuming sexual reproduction after a single male is cloned, which should be especially useful for reviving extinct or endangered species.
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Regulatory Forum commentary: alternative mouse models for future cancer risk assessment.
Morton, Daniel; Sistare, Frank D; Nambiar, Prashant R; Turner, Oliver C; Radi, Zaher; Bower, Nancy
2014-07-01
International regulatory and pharmaceutical industry scientists are discussing revision of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) S1 guidance on rodent carcinogenicity assessment of small molecule pharmaceuticals. A weight-of-evidence approach is proposed to determine the need for rodent carcinogenicity studies. For compounds with high human cancer risk, the product may be labeled appropriately without conducting rodent carcinogenicity studies. For compounds with minimal cancer risk, only a 6-month transgenic mouse study (rasH2 mouse or p53+/- mouse) or a 2-year mouse study would be needed. If rodent carcinogenicity testing may add significant value to cancer risk assessment, a 2-year rat study and either a 6-month transgenic mouse or a 2-year mouse study is appropriate. In many cases, therefore, one rodent carcinogenicity study could be sufficient. The rasH2 model predicts neoplastic findings relevant to human cancer risk assessment as well as 2-year rodent models, produces fewer irrelevant neoplastic outcomes, and often will be preferable to a 2-year rodent study. Before revising ICH S1 guidance, a prospective evaluation will be conducted to test the proposed weight-of-evidence approach. This evaluation offers an opportunity for a secondary analysis comparing the value of alternative mouse models and 2-year rodent studies in the proposed ICH S1 weight-of-evidence approach for human cancer risk assessment. © 2014 by The Author(s).
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Decerebrate mouse model for studies of the spinal cord circuits
DEFF Research Database (Denmark)
Meehan, Claire Francesca; Mayr, Kyle A; Manuel, Marin
2017-01-01
The adult decerebrate mouse model (a mouse with the cerebrum removed) enables the study of sensory-motor integration and motor output from the spinal cord for several hours without compromising these functions with anesthesia. For example, the decerebrate mouse is ideal for examining locomotor be......, which is ample time to perform most short-term procedures. These protocols can be modified for those interested in cardiovascular or respiratory function in addition to motor function and can be performed by trainees with some previous experience in animal surgery....
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International Nuclear Information System (INIS)
Schnieke, A.; Dziadek, M.; Bateman, J.; Mascara, T.; Harbers, K.; Gelinas, R.; Jaenisch, R.
1987-01-01
The Mov-13 mouse strain carries a retroviral insertion in the proα1(I) collagen gene that prevents transcription of the gene. Cell lines derived from homozygous embryos do not express type I collagen although normal amounts of proα2 mRNA are synthesized. The authors have introduced genomic clones of either the human or mouse proα1(I) collagen gene into homozygous cell lines to assess whether the human or mouse proα1(I) chains can associate with the endogenous mouse proα2(I) chain to form stable type I collagen. The human gene under control of the simian virus 40 promoter was efficiently transcribed in the transfected cells. Protein analyses revealed that stable heterotrimers consisting of two human α1 chains and one mouse α2 chain were formed and that type I collagen was secreted by the transfected cells at normal rates. However, the electrophoretic migration of both α1(I) and α2(I) chains in the human-mouse hybrid molecules were retarded, compared to the α(I) chains in control mouse cells. Inhibition of the posttranslational hydroxylation of lysine and proline resulted in comigration of human and mouse α1 and α2 chains, suggesting that increased posttranslational modification caused the altered electrophoretic migration in the human-mouse hybrid molecules. Amino acid sequence differences between the mouse and human α chains may interfere with the normal rate of helix formation and increase the degree of posttranslational modifications similar to those observed in patients with lethal perinatal osteogenesis imperfecta. The Mov-13 mouse system should allow the authors to study the effect specific mutations introduced in transfected proα1(I) genes have on the synthesis, assembly, and function of collagen I
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International Nuclear Information System (INIS)
Kaji, Chiaki; Tsujimoto, Yuta; Kato Kaneko, Mika; Kato, Yukinari; Sawa, Yoshihiko
2012-01-01
This study aims to develop new monoclonal antibodies (mAbs) against mouse and human podoplanin. Rats were immunized with synthetic peptides, corresponding to amino acids 38–51 of mouse podoplanin or human podoplanin which is 100% homologous to the same site of monkey podoplanin; anti-mouse podoplanin mAb PMab-1 (IgG 2a ) and anti-human mAb NZ-1.2 (IgG 2a ) were established. In immunocytochemistry, the mouse melanoma B16-F10 and mouse podoplanin (mPDPN)-expressed CHO transfectant were stained by PMab-1; human lymphatic endothelial cells (LEC) and human podoplanin (hPDPN)-expressed squamous cell carcinoma HSC3 transfectant, were stained by NZ-1.2. Western-blot analysis detected an about 40-kDa protein in CHO-mPDPN and B16-F10 by PMab-1, and in HSC3-hPDPN and LEC by NZ-1.2. In frozen sections, PMab-1 reacted with mouse kidney, pulmonary alveoli, pulmonary pleura, and salivary gland myoepithelial cells while NZ-1.2 reacted to the human salivary gland myoepithelial cells. The immunostaining of paraffin-embedded sections also showed the reaction of PMab-1 or NZ-1.2 to the mouse or monkey kidney glomerulus, pulmonary alveoli, and lung lymphatic vessels. These results indicate that the two novel rat mAbs to the mouse and human/monkey podoplanin are useful for Western-blot and immunostaining of somatic tissues on paraffin-embedded sections as well as frozen sections
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Genomes of the Mouse Collaborative Cross.
Srivastava, Anuj; Morgan, Andrew P; Najarian, Maya L; Sarsani, Vishal Kumar; Sigmon, J Sebastian; Shorter, John R; Kashfeen, Anwica; McMullan, Rachel C; Williams, Lucy H; Giusti-Rodríguez, Paola; Ferris, Martin T; Sullivan, Patrick; Hock, Pablo; Miller, Darla R; Bell, Timothy A; McMillan, Leonard; Churchill, Gary A; de Villena, Fernando Pardo-Manuel
2017-06-01
The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 30× coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of
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Mass spectrometry analysis of hepcidin peptides in experimental mouse models.
Directory of Open Access Journals (Sweden)
Harold Tjalsma
Full Text Available The mouse is a valuable model for unravelling the role of hepcidin in iron homeostasis, however, such studies still report hepcidin mRNA levels as a surrogate marker for bioactive hepcidin in its pivotal function to block ferroportin-mediated iron transport. Here, we aimed to assess bioactive mouse Hepcidin-1 (Hep-1 and its paralogue Hepcidin-2 (Hep-2 at the peptide level. To this purpose, Fourier transform ion cyclotron resonance (FTICR and tandem-MS was used for hepcidin identification, after which a time-of-flight (TOF MS-based methodology was exploited to routinely determine Hep-1 and -2 levels in mouse serum and urine. This method was biologically validated by hepcidin assessment in: i 3 mouse strains (C57Bl/6; DBA/2 and BABL/c upon stimulation with intravenous iron and LPS, ii homozygous Hfe knock out, homozygous transferrin receptor 2 (Y245X mutated mice and double affected mice, and iii mice treated with a sublethal hepatotoxic dose of paracetamol. The results showed that detection of Hep-1 was restricted to serum, whereas Hep-2 and its presumed isoforms were predominantly present in urine. Elevations in serum Hep-1 and urine Hep-2 upon intravenous iron or LPS were only moderate and varied considerably between mouse strains. Serum Hep-1 was decreased in all three hemochromatosis models, being lowest in the double affected mice. Serum Hep-1 levels correlated with liver hepcidin-1 gene expression, while acute liver damage by paracetamol depleted Hep-1 from serum. Furthermore, serum Hep-1 appeared to be an excellent indicator of splenic iron accumulation. In conclusion, Hep-1 and Hep-2 peptide responses in experimental mouse agree with the known biology of hepcidin mRNA regulators, and their measurement can now be implemented in experimental mouse models to provide novel insights in post-transcriptional regulation, hepcidin function, and kinetics.
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A surgical approach appropriate for targeted cochlear gene therapy in the mouse.
Jero, J; Tseng, C J; Mhatre, A N; Lalwani, A K
2001-01-01
Therapeutic manipulations of the mammalian cochlea, including cochlear gene transfer, have been predominantly studied using the guinea pig as the experimental model. With the significant developments in mouse genomics and the availability of mutant strains of mice with well-characterized hearing loss, the mouse justifiably will be the preferred animal model for therapeutic manipulations. However, the potential advantages of the mouse model have not been fully realized due to the surgical difficulty of accessing its small cochlea. This study describes a ventral approach, instead of the routinely used postauricular approach in other rodents, for accessing the mouse middle and inner ear, and its application in cochlear gene transfer. This ventral approach enabled rapid and direct delivery of liposome-transgene complex to the mouse inner ear while avoiding blood loss, facial nerve morbidity, and mortality. Transgene expression at 3 days was detected in Reissner's membrane, spiral limbus, spiral ligament, and spiral ganglion cells, in a pattern similar to that previously described in the guinea pig. The successful access and delivery of material to the mouse cochlea and the replication of gene expression seen in the guinea pig demonstrated in this study should promote the use of the mouse in future studies investigating targeted cochlear therapy.
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Understanding Cancer Prognosis
Full Text Available ... Centers Advisory Boards & Review Groups Budget & Appropriations Current Year Budget Annual Plan & Budget Proposal Congressional Justification NCI ... using statistics that researchers have collected over many years about people with the same type of cancer. ...
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Nrl-Cre transgenic mouse mediates loxP recombination in developing rod photoreceptors.
Brightman, Diana S; Razafsky, David; Potter, Chloe; Hodzic, Didier; Chen, Shiming
2016-03-01
The developing mouse retina is a tractable model for studying neurogenesis and differentiation. Although transgenic Cre mouse lines exist to mediate conditional genetic manipulations in developing mouse retinas, none of them act specifically in early developing rods. For conditional genetic manipulations of developing retinas, a Nrl-Cre mouse line in which the Nrl promoter drives expression of Cre in rod precursors was created. The results showed that Nrl-Cre expression was specific to the retina where it drives rod-specific recombination with a temporal pattern similar to endogenous Nrl expression during retinal development. This Nrl-Cre transgene does not negatively impact retinal structure and function. Taken together, the data suggested that the Nrl-Cre mouse line was a valuable tool to drive Cre-mediated recombination specifically in developing rods. © 2016 Wiley Periodicals, Inc.
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The alpha-spectrin gene is on chromosome 1 in mouse and man.
Huebner, K; Palumbo, A P; Isobe, M; Kozak, C A; Monaco, S; Rovera, G; Croce, C M; Curtis, P J
1985-06-01
By using alpha-spectrin cDNA clones of murine and human origin and somatic cell hybrids segregating either mouse or human chromosomes, the gene for alpha-spectrin has been mapped to chromosome 1 in both species. This assignment of the mouse alpha-spectrin gene to mouse chromosome 1 by DNA hybridization strengthens the previous identification of the alpha-spectrin locus in mouse with the sph locus, which previously was mapped by linkage analysis to mouse chromosome 1, distal to the Pep-3 locus. By in situ hybridization to human metaphase chromosomes, the human alpha-spectrin gene has been localized to 1q22-1q25; interestingly, the locus for a non-Rh-linked form of elliptocytosis has been provisionally mapped to band 1q2 by family linkage studies.
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International Nuclear Information System (INIS)
Marques-Carvalho, Maria João; Morais-Cabral, João Henrique
2012-01-01
The crystallization conditions and preliminary crystal characterization of the cytoplasmic cyclic nucleotide-binding homology domain from the mouse EAG potassium channel are reported. The members of the family of voltage-gated KCNH potassium channels play important roles in cardiac and neuronal repolarization, tumour proliferation and hormone secretion. These channels have a C-terminal cytoplasmic domain which is homologous to cyclic nucleotide-binding domains (CNB-homology domains), but it has been demonstrated that channel function is not affected by cyclic nucleotides and that the domain does not bind nucleotides in vitro. Here, the crystallization and preliminary crystallographic analysis of a CNB-homology domain from a member of the KCNH family, the mouse EAG channel, is reported. X-ray diffraction data were collected to 2.2 Å resolution and the crystal belonged to the hexagonal space group P3 1 21
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SU-F-T-668: Irradiating Mouse Brain with a Clinical Linear Accelerator
Energy Technology Data Exchange (ETDEWEB)
Perez-Torres, C [N Rancilio Purdue University, West Lafayette, IN (United States)
2016-06-15
Purpose: To design and construct a “mouse jig” device that would allow for irradiation of the mouse brain with a clinical Varian 6 MeV Linear Accelerator. This device must serve as a head immobilizer, gaseous anesthesia delivery, and radiation bolus concurrently. Methods: The mouse jig was machined out of nylon given that it is inexpensive, easy to machine, and has similar electron density to water. A cylindrical opening with diameter of 16 mm and 40 mm depth was drilled into a nylon block sized 56×56×50 mm (width, length, depth). Additional slots were included in the block for ear bars and a tooth bar to serve as a three-point immobilization device as well as for anesthesia delivery and scavenging. For ease of access when loading the mouse into the holder, there is a removable piece at the top of the block that is 15 mm in depth. This serves a dual purpose, as with the proper extra shielding, the mouse jig could be used with lower linear energy transfer photons with this piece removed. A baseplate was then constructed with five square slots where the mouse jig can securely be inserted plus additional slots that would allow the baseplate to be mounted on a standard lock bar in the treatment couch. This maximizes the reproducibility of placement between imaging and treatment and between treatment sessions. Results: CT imaging and radiation treatment planning was performed that showed acceptable coverage and uniformity of radiation dose in the mouse brain while sparing the throat and eyes. Conclusion: We have designed and manufactured a device that fulfills our criteria allowing us to selectively irradiate the mouse brain with a clinical linear accelerator. This setup will be used for generating mouse models of radiation-induced brain injury.
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Directory of Open Access Journals (Sweden)
Ivanna Ihnatovych
Full Text Available Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C. Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate- cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.
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Cloning, characterization and targeting of the mouse HEXA gene
Energy Technology Data Exchange (ETDEWEB)
Wakamatsu, N.; Trasler, J.M.; Gravel, R.A. [McGill Univ., Quebec (Canada)] [and others
1994-09-01
The HEXA gene, encoding the {alpha} subunit of {beta}-hexosaminidase A, is essential for the metabolism of ganglioside G{sub M2}, and defects in this gene cause Tay-Sachs disease in humans. To elucidate the role of the gene in the nervous system of the mouse and to establish a mouse model of Tay-Sachs disease, we have cloned and characterized the HEXA gene and targeted a disruption of the gene in mouse ES cells. The mouse HEXA gene spans {approximately}26 kb and consists of 14 exons, similar to the human gene. A heterogeneous transcription initiation site was identified 21-42 bp 5{prime} of the initiator ATG, with two of the sites fitting the consensus CTCA (A = start) as seen for some weak initiator systems. Promoter analysis showed that the first 150 bp 5{prime} of the ATG contained 85% of promoter activity observed in constructs containing up to 1050 bp of 5{prime} sequence. The active region contained a sequence matching that of the adenovirus major late promoter upstream element factor. A survey of mouse tissues showed that the highest mRNA levels were in (max to min): testis (5.5 x brain cortex), adrenal, epididymis, heart, brain, lung, kidney, and liver (0.3 x brain cortex). A 12 kb BstI/SalI fragment containing nine exons was disrupted with the insertion of the bacterial neo{sup r} gene in exon 11 and was targeted into 129/Sv ES cells by homologous recombination. Nine of 153 G418 resistant clones were correctly targeted as confirmed by Southern blotting. The heterozygous ES cells were microinjected into mouse blastocysts and implanted into pseudo-pregnant mice. Nine male chimeric mice, showing that 40-95% chimerism for the 129/Sv agouti coat color marker, are being bred in an effort to generate germline transmission of the disrupted HEXA gene.
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Humanized mouse models: Application to human diseases.
Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru
2018-05-01
Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.
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Mouse Model of Burn Wound and Infection
DEFF Research Database (Denmark)
Calum, Henrik; Høiby, Niels; Moser, Claus
2017-01-01
The immunosuppression induced by thermal injury renders the burned victim susceptible to infection. A mouse model was developed to examine the immunosuppression, which was possible to induce even at a minor thermal insult of 6% total body surface area. After induction of the burn (48 hr) a depres......The immunosuppression induced by thermal injury renders the burned victim susceptible to infection. A mouse model was developed to examine the immunosuppression, which was possible to induce even at a minor thermal insult of 6% total body surface area. After induction of the burn (48 hr...
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Genetic analysis of radiation-induced mouse thymic lymphomas
International Nuclear Information System (INIS)
Kominami, R.; Wakabayashi, Y.; Niwa, O.
2003-01-01
Mouse thymic lymphomas are one of the classic models of radiation-induced malignancies, and the model has been used for the study of genes involved in carcinogenesis. ras oncogenes are the first isolate which undergoes mutations in 10 to 30 % of lymphomas, and p16INK4a and p19ARF in the INK4a-ARF locus are also frequently inactivated. In our previous study, the inactivation of Ikaros, a key regurator of lymphoid system, was found in those lymphomas, and it was suggested that there are other responsible genes yet to be discovered. On the other hand, genetic predisposition to radiation-induced lymphoma often differs in different strains, and this reflects the presence of low penetrance genes that can modify the impact of a given mutation. Little study of such modifiers or susceptibility genes has been performed, either. Recent availability of databases on mouse genome information and the power of mouse genetic system underline usefulness of the lymphoma model in search for novel genes involved, which may provide clues to molecular mechanisms of development of the radiogenic lymphoma and also genes involved in human lymphomas and other malignancies. Accordingly, we have carried out positional cloning for the two different types of tumor-related genes. In this symposium, our current progress is presented that includes genetic mapping of susceptibility/ resistance loci on mouse chromosomes 4, 5 and 19, and also functional analysis of a novel tumor suppressor gene, Rit1/Bcl11b, that has been isolated from allelic loss (LOH) mapping and sequence analysis for γ -ray induced mouse thymic lymphomas
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Directory of Open Access Journals (Sweden)
Uddhav P. Kelavkar
2006-06-01
Full Text Available The incidence and mortality of prostate cancer (PCa vary greatly in different geographic regions, for which lifestyle factors, such as dietary fat intake, have been implicated. Human 15-lipoxygenase-1 (h15-LO-1, which metabolizes polyunsaturated fatty acids, is a highly regulated, tissue-specific, lipid-peroxidating enzyme that functions in physiological membrane remodeling and in the pathogenesis of atherosclerosis, inflammation, and carcinogenesis. We have shown that aberrant overexpression of 15-LO-1 occurs in human PCa, particularly high-grade PCa, and in high-grade prostatic intraepithelial neoplasia (HGPIN, and that the murine orthologue is increased in SV40-based genetically engineered mouse (GEM models of PCa, such as LADY and TRansgenic Adenocarcinoma of Mouse Prostate. To further define the role of 15-LO-1 in prostate carcinogenesis, we established a novel GEM model with targeted overexpression of h15-LO-1 in the prostate [human fifteen lipoxygenase-1 in mouse prostate (FLiMP]. We used a Cre- mediated and a loxP-mediated recombination strategy to target h15-LO-1 specifically to the prostate of C57BL/6 mice. Wild-type (wt, FLiMP+/-, and FLiMP+/+ mice aged 7 to 21, 24 to 28, and 35 weeks were characterized by histopathology, immunohistochemistry (IHC, and DNA/RNA and enzyme analyses. Compared to wt mice, h15-LO-1 enzyme activity was increased similarly in both homozygous FLiMP+/+ and hemizygous FLiMP+/- prostates. Dorsolateral and ventral prostates of FLiMP mice showed focal and progressive epithelial hyperplasia with nuclear atypia, indicative of the definition of mouse prostatic intraepithelial neoplasia (mPIN according to the National Cancer Institute. These foci showed increased proliferation by Ki-67 IHC. No progression to invasive PCa was noted up to 35 weeks. By IHC, h15-LO-1 expression was limited to luminal epithelial cells, with increased expression in mPIN foci (similar to human HGPIN. In summary, targeted overexpression of h
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Modulation of hepatocyte growth factor gene expression by estrogen in mouse ovary.
Liu, Y; Lin, L; Zarnegar, R
1994-09-01
Hepatocyte growth factor (HGF) is expressed in a variety of tissues and cell types under normal conditions and in response to various stimuli such as tissue injury. In the present study, we demonstrate that the transcription of the HGF gene is stimulated by estrogen in mouse ovary. A single injection of 17 beta-estradiol results in a dramatic and transient elevation of the levels of mouse HGF mRNA. Sequence analysis has found that two putative estrogen responsive elements (ERE) reside at -872 in the 5'-flanking region and at +511 in the first intron, respectively, of the mouse HGF gene. To test whether these ERE elements are responsible for estrogen induction of HGF gene expression, chimeric plasmids containing variable regions of the 5'-flanking sequence of HGF gene and the coding region for chloramphenicol acetyltransferase (CAT) gene were transiently transfected into both human endometrial carcinoma RL 95-2 cells and mouse fibroblast NIH 3T3 cells to assess hormone responsiveness. Transfection results indicate that the ERE elements of the mouse HGF gene can confer estrogen action to either homologous or heterologous promoters. Nuclear protein extracts either from RL95-2 cells transfected with the estrogen receptor expression vector or from mouse liver bound in vitro to ERE elements specifically, as shown by band shift assay. Therefore, our results demonstrate that the HGF gene is transcriptionally regulated by estrogen in mouse ovary; and such regulation is mediated via a direct interaction of the estrogen receptor complex with cis-acting ERE elements identified in the mouse HGF gene.
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Directory of Open Access Journals (Sweden)
Jelena Reste
2015-08-01
Full Text Available Computer work is characterized by sedentary static workload with low-intensity energy metabolism. The aim of our study was to evaluate the dynamics of skin surface temperature in the hand during prolonged computer mouse work under different ergonomic setups. Digital infrared imaging of the right forearm and wrist was performed during three hours of continuous computer work (measured at the start and every 15 minutes thereafter in a laboratory with controlled ambient conditions. Four people participated in the study. Three different ergonomic computer mouse setups were tested on three different days (horizontal computer mouse without mouse pad; horizontal computer mouse with mouse pad and padded wrist support; vertical computer mouse without mouse pad. The study revealed a significantly strong negative correlation between the temperature of the dorsal surface of the wrist and time spent working with a computer mouse. Hand skin temperature decreased markedly after one hour of continuous computer mouse work. Vertical computer mouse work preserved more stable and higher temperatures of the wrist (>30 °C, while continuous use of a horizontal mouse for more than two hours caused an extremely low temperature (<28 °C in distal parts of the hand. The preliminary observational findings indicate the significant effect of the duration and ergonomics of computer mouse work on the development of hand hypothermia.
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Trb2, a mouse homolog of tribbles, is dispensable for kidney and mouse development
International Nuclear Information System (INIS)
Takasato, Minoru; Kobayashi, Chiyoko; Okabayashi, Koji; Kiyonari, Hiroshi; Oshima, Naoko; Asashima, Makoto; Nishinakamura, Ryuichi
2008-01-01
Glomeruli comprise an important filtering apparatus in the kidney and are derived from the metanephric mesenchyme. A nuclear protein, Sall1, is expressed in this mesenchyme, and we previously reported that Trb2, a mouse homolog of Drosophila tribbles, is expressed in the mesenchyme-derived tissues of the kidney by microarray analyses using Sall1-GFP knock-in mice. In the present report, we detected Trb2 expression in a variety of organs during gestation, including the kidneys, mesonephros, testes, heart, eyes, thymus, blood vessels, muscle, bones, tongue, spinal cord, and ganglions. In the developing kidney, Trb2 signals were detected in podocytes and the prospective mesangium of the glomeruli, as well as in ureteric bud tips. However, Trb2 mutant mice did not display any apparent phenotypes and no proteinuria was observed, indicating normal glomerular functions. These results suggest that Trb2 plays minimal roles during kidney and mouse development
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Mouse Activity across Time Scales: Fractal Scenarios
Lima, G. Z. dos Santos; Lobão-Soares, B.; do Nascimento, G. C.; França, Arthur S. C.; Muratori, L.; Ribeiro, S.; Corso, G.
2014-01-01
In this work we devise a classification of mouse activity patterns based on accelerometer data using Detrended Fluctuation Analysis. We use two characteristic mouse behavioural states as benchmarks in this study: waking in free activity and slow-wave sleep (SWS). In both situations we find roughly the same pattern: for short time intervals we observe high correlation in activity - a typical 1/f complex pattern - while for large time intervals there is anti-correlation. High correlation of short intervals ( to : waking state and to : SWS) is related to highly coordinated muscle activity. In the waking state we associate high correlation both to muscle activity and to mouse stereotyped movements (grooming, waking, etc.). On the other side, the observed anti-correlation over large time scales ( to : waking state and to : SWS) during SWS appears related to a feedback autonomic response. The transition from correlated regime at short scales to an anti-correlated regime at large scales during SWS is given by the respiratory cycle interval, while during the waking state this transition occurs at the time scale corresponding to the duration of the stereotyped mouse movements. Furthermore, we find that the waking state is characterized by longer time scales than SWS and by a softer transition from correlation to anti-correlation. Moreover, this soft transition in the waking state encompass a behavioural time scale window that gives rise to a multifractal pattern. We believe that the observed multifractality in mouse activity is formed by the integration of several stereotyped movements each one with a characteristic time correlation. Finally, we compare scaling properties of body acceleration fluctuation time series during sleep and wake periods for healthy mice. Interestingly, differences between sleep and wake in the scaling exponents are comparable to previous works regarding human heartbeat. Complementarily, the nature of these sleep-wake dynamics could lead to a better
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Menet, Marie-Claude; Marchal, Julia; Dal-Pan, Alexandre; Taghi, Méryam; Nivet-Antoine, Valérie; Dargère, Delphine; Laprévote, Olivier; Beaudeux, Jean-Louis; Aujard, Fabienne; Epelbaum, Jacques; Cottart, Charles-Henry
2014-01-01
The grey mouse lemur (Microcebus murinus) is a non-human primate used to study the ageing process. Resveratrol is a polyphenol that may increase lifespan by delaying age-associated pathologies. However, no information about resveratrol absorption and metabolism is available for this primate. Resveratrol and its metabolites were qualitatively and quantitatively analyzed in male mouse-lemur plasma (after 200 mg.kg−1 of oral resveratrol) by ultra-high performance liquid chromatography (UHPLC), coupled to a quadrupole-time-of-flight (Q-TOF) mass spectrometer used in full-scan mode. Data analyses showed, in MSE mode, an ion common to resveratrol and all its metabolites: m/z 227.072, and an ion common to dihydro-resveratrol metabolites: m/z 229.08. A semi-targeted study enabled us to identify six hydrophilic resveratrol metabolites (one diglucurono-conjugated, two monoglucurono-conjugated, one monosulfo-conjugated and two both sulfo- and glucurono-conjugated derivatives) and three hydrophilic metabolites of dihydro-resveratrol (one monoglucurono-conjugated, one monosulfo-conjugated, and one both sulfo- and glucurono-conjugated derivatives). The presence of such metabolites has been already detected in the mouse, rat, pig, and humans. Free resveratrol was measurable for several hours in mouse-lemur plasma, and its two main metabolites were trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate. Free dihydro-resveratrol was not measurable whatever the time of plasma collection, while its hydrophilic metabolites were present at 24 h after intake. These data will help us interpret the effect of resveratrol in mouse lemurs and provide further information on the inter-species characteristics of resveratrol metabolism. PMID:24663435
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Diffusion of [2-14C]diazepam across hairless mouse skin and human skin
International Nuclear Information System (INIS)
Koch, R.L.; Palicharla, P.; Groves, M.J.
1987-01-01
The objectives of this study were to investigate the absorption of diazepam applied topically to the hairless mouse in vivo and to determine the diffusion of diazepam across isolated hairless mouse skin and human skin. [ 14 C]Diazepam was readily absorbed after topical administration to the intact hairless mouse, a total of 75.8% of the 14 C-label applied being recovered in urine and feces. Diazepam was found to diffuse across human and hairless mouse skin unchanged in experiments with twin-chambered diffusion cells. The variation in diffusion rate or the flux for both human and mouse tissues was greater among specimens than between duplicate or triplicate trials for a single specimen. Fluxes for mouse skin (stratum corneum, epidermis, and dermis) were greater than for human skin (stratum corneum and epidermis): 0.35-0.61 microgram/cm2/h for mouse skin vs 0.24-0.42 microgram/cm2/h for human skin. The permeability coefficients for mouse skin ranged from 1.4-2.4 X 10(-2)cm/h compared with 0.8-1.4 X 10(-2)cm/h for human skin. Although human stratum corneum is almost twice the thickness of that of the hairless mouse, the diffusion coefficients for human skin were 3-12 times greater (0.76-3.31 X 10(-6) cm2/h for human skin vs 0.12-0.27 X 10(-6) cm2/h for hairless mouse) because of a shorter lag time for diffusion across human skin. These differences between the diffusion coefficients and diffusion rates (or permeability coefficients) suggest that the presence of the dermis may present some barrier properties. In vitro the dermis may require complete saturation before the diazepam can be detected in the receiving chamber
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Mouse Models of the Skin: Models to Define Mechanisms of Skin Carcinogenesis
International Nuclear Information System (INIS)
Wheeler, D. L.; Verma, A. K.; Denning, M. F.
2013-01-01
The multistep model of mouse skin carcinogenesis has facilitated identification of irreversible genetic events of initiation and progression, and epigenetic events of tumor promotion. Mouse skin tumor initiation can be accomplished by a single exposure to a sufficiently small dose of a carcinogen, and this step is rapid and irreversible. However, promotion of skin tumor formation requires a repeated and prolonged exposure to a promoter, and that tumor promotion is reversible. Investigations focused on the mechanisms of mouse carcinogenesis have resulted in the identifications of potential molecular targets of cancer induction and progression useful in planning strategies for human cancer prevention trials. This special issue contains eight papers that focus on mouse models used to study individual proteins expressed in the mouse skin and the role they play in differentiation, tissue homeostasis, skin carcinogenesis, and chemo prevention of skin cancer.
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Immunologic applications of conditional gene modification technology in the mouse.
Sharma, Suveena; Zhu, Jinfang
2014-04-02
Since the success of homologous recombination in altering mouse genome and the discovery of Cre-loxP system, the combination of these two breakthroughs has created important applications for studying the immune system in the mouse. Here, we briefly summarize the general principles of this technology and its applications in studying immune cell development and responses; such implications include conditional gene knockout and inducible and/or tissue-specific gene over-expression, as well as lineage fate mapping. We then discuss the pros and cons of a few commonly used Cre-expressing mouse lines for studying lymphocyte development and functions. We also raise several general issues, such as efficiency of gene deletion, leaky activity of Cre, and Cre toxicity, all of which may have profound impacts on data interpretation. Finally, we selectively list some useful links to the Web sites as valuable mouse resources. Copyright © 2014 John Wiley & Sons, Inc.
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Effect of low dose radiation on apoptosis in mouse spleen
International Nuclear Information System (INIS)
Chen Dong; Liu Jiamei; Chen Aijun; Liu Shuzheng
1999-01-01
Objective: To study the effect of whole body irradiation (WBI) with different doses of X-ray on apoptosis in mouse spleen. Methods: Time course changes and dose-effect relationship of apoptosis in mouse spleen induced by WBI were observed with transmission electron microscopy (TEM) qualitatively and TUNEL method semi-quantitatively. Results: Many typical apoptotic lymphocytes were found by TEM in mouse spleen after WBI with 2 Gy. No marked alterations of ultrastructure were found following WBI with 0.075 Gy. It was observed by TUNEL that the apoptosis of splenocytes increased after high dose radiation and decreased following low dose radiation (LDR). The dose-effect relationship of radiation-induced apoptosis showed a J-shaped curve. Conclusion: The effect of different doses of ionizing radiation on apoptosis in mouse spleen was distinct. And the decrease of apoptosis after LDR is considered a manifestation of radiation hormesis
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Robust and sensitive analysis of mouse knockout phenotypes.
Directory of Open Access Journals (Sweden)
Natasha A Karp
Full Text Available A significant challenge of in-vivo studies is the identification of phenotypes with a method that is robust and reliable. The challenge arises from practical issues that lead to experimental designs which are not ideal. Breeding issues, particularly in the presence of fertility or fecundity problems, frequently lead to data being collected in multiple batches. This problem is acute in high throughput phenotyping programs. In addition, in a high throughput environment operational issues lead to controls not being measured on the same day as knockouts. We highlight how application of traditional methods, such as a Student's t-Test or a 2-way ANOVA, in these situations give flawed results and should not be used. We explore the use of mixed models using worked examples from Sanger Mouse Genome Project focusing on Dual-Energy X-Ray Absorptiometry data for the analysis of mouse knockout data and compare to a reference range approach. We show that mixed model analysis is more sensitive and less prone to artefacts allowing the discovery of subtle quantitative phenotypes essential for correlating a gene's function to human disease. We demonstrate how a mixed model approach has the additional advantage of being able to include covariates, such as body weight, to separate effect of genotype from these covariates. This is a particular issue in knockout studies, where body weight is a common phenotype and will enhance the precision of assigning phenotypes and the subsequent selection of lines for secondary phenotyping. The use of mixed models with in-vivo studies has value not only in improving the quality and sensitivity of the data analysis but also ethically as a method suitable for small batches which reduces the breeding burden of a colony. This will reduce the use of animals, increase throughput, and decrease cost whilst improving the quality and depth of knowledge gained.
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Garton, Andrew J; Crew, Andrew P A; Franklin, Maryland; Cooke, Andrew R; Wynne, Graham M; Castaldo, Linda; Kahler, Jennifer; Winski, Shannon L; Franks, April; Brown, Eric N; Bittner, Mark A; Keily, John F; Briner, Paul; Hidden, Chris; Srebernak, Mary C; Pirrit, Carrie; O'Connor, Matthew; Chan, Anna; Vulevic, Bojana; Henninger, Dwight; Hart, Karen; Sennello, Regina; Li, An-Hu; Zhang, Tao; Richardson, Frank; Emerson, David L; Castelhano, Arlindo L; Arnold, Lee D; Gibson, Neil W
2006-01-15
OSI-930 is a novel inhibitor of the receptor tyrosine kinases Kit and kinase insert domain receptor (KDR), which is currently being evaluated in clinical studies. OSI-930 selectively inhibits Kit and KDR with similar potency in intact cells and also inhibits these targets in vivo following oral dosing. We have investigated the relationships between the potency observed in cell-based assays in vitro, the plasma exposure levels achieved following oral dosing, the time course of target inhibition in vivo, and antitumor activity of OSI-930 in tumor xenograft models. In the mutant Kit-expressing HMC-1 xenograft model, prolonged inhibition of Kit was achieved at oral doses between 10 and 50 mg/kg and this dose range was associated with antitumor activity. Similarly, prolonged inhibition of wild-type Kit in the NCI-H526 xenograft model was observed at oral doses of 100 to 200 mg/kg, which was the dose level associated with significant antitumor activity in this model as well as in the majority of other xenograft models tested. The data suggest that antitumor activity of OSI-930 in mouse xenograft models is observed at dose levels that maintain a significant level of inhibition of the molecular targets of OSI-930 for a prolonged period. Furthermore, pharmacokinetic evaluation of the plasma exposure levels of OSI-930 at these effective dose levels provides an estimate of the target plasma concentrations that may be required to achieve prolonged inhibition of Kit and KDR in humans and which would therefore be expected to yield a therapeutic benefit in future clinical evaluations of OSI-930.
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Using the Scroll Wheel on a Wireless Mouse as a Motion Sensor
Taylor, Richard S.; Wilson, William R.
2010-01-01
Since its inception in the mid-80s, the computer mouse has undergone several design changes. As the mouse has evolved, physicists have found new ways to utilize it as a motion sensor. For example, the rollers in a mechanical mouse have been used as pulleys to study the motion of a magnet moving through a copper tube as a quantitative demonstration…
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Experimental photoallergic contact dermatitis: a mouse model
International Nuclear Information System (INIS)
Maguire, H.C. Jr.; Kaidbey, K.
1982-01-01
We have induced photoallergic contact dermatitis in mice to 3,3',4',5 tetrachlorosalicylanilide (TCSA), chlorpromazine and 6-methylcoumarin. These compounds are known to produce photoallergic contact dermatitis in humans. The photoallergic contact dermatitis reaction in the mouse is immunologically specific viz. mice photosensitized to TCSA react, by photochallenge, to that compound and not to chlorpromazine, and conversely. The reaction requires UVA at both sensitization and challenge. It appears to be T-cell mediated in that it can be passively transferred to syngeneic mice by lymph node cells from actively sensitized mice, the histology of the reactions resembles that of classic allergic contact dermatitis in mice, challenge reactions are seen at 24 but not at 4 hr, and photoallergic contact dermatitis can be induced in B-cell deficient mice. The availability of a mouse model for the study of photo-ACD will facilitate the identification of pertinent control mechanisms and may aid in the management of the disease. It is likely that a bioassay for photoallergens of humans can be based on this mouse model
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Mouse allergen-specific immunoglobulin G4 and risk of mouse skin test sensitivity
Matsui, E. C.; Diette, G. B.; Krop, E. J. M.; Aalberse, R. C.; Smith, A. L.; Eggleston, P. A.
2006-01-01
High serum levels of cat-specific IgG and IgG4 are associated with protection against allergic sensitization to cat, but whether this association applies to other animal allergens remains unclear. To determine if high levels of mouse-specific IgG and IgG4 are associated with a decreased risk of
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Darwish, A D; Helal, A M; Aly El-Din, N H; Solaiman, L L; Amin, A
2017-02-01
The aim is to identify the epidemiological and clinicopathological features associated with young breast cancer (BC) patients and to discuss factors affecting tumor recurrence and DFS. A retrospective analysis was conducted based on medical records from young females patients aged ≤35 years with pathologically confirmed primary breast cancer treated during 2008-2010 at NCI. Cases with non invasive cancer and non carcinoma histology are excluded. Of the 5408 cases diagnosed with breast cancer, 554 were young. Four hundred & fifty eight patients representing 9.2% were within our inclusion criteria. Almost half of the patients (45.9%) presented with stage III. Axillary nodes involvement was in 63.9%, 83.3% were grade 2. More than one quarter of tumors was hormone receptors negative (28.8%) & Her2 was over-expressed in 30%. Mastectomy was offered in 72% while conservative breast surgery in 26%, 69.2% received chemotherapy either adjuvant, neoadjuvant or both, 82.5% received adjuvant radiotherapy, 68.6% received hormonal therapy. Metastatic disease developed in 51.3%, with 31% having more than one site of metastases. After a median follow up period of 66 months, the median DFS of patients was 60 months. The median DFS was significantly shorter among patients with positive lymph nodes (P Breast cancer in young women is aggressive from the time of diagnosis. Our results provide baseline data of young BC in the Middle East & North Africa region; thus, contributing to future epidemiological and hospital-based researches. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Gene expression patterns associated with neurological disease in human HIV infection.
Directory of Open Access Journals (Sweden)
Pietro Paolo Sanna
Full Text Available The pathogenesis and nosology of HIV-associated neurological disease (HAND remain incompletely understood. Here, to provide new insight into the molecular events leading to neurocognitive impairments (NCI in HIV infection, we analyzed pathway dysregulations in gene expression profiles of HIV-infected patients with or without NCI and HIV encephalitis (HIVE and control subjects. The Gene Set Enrichment Analysis (GSEA algorithm was used for pathway analyses in conjunction with the Molecular Signatures Database collection of canonical pathways (MSigDb. We analyzed pathway dysregulations in gene expression profiles of patients from the National NeuroAIDS Tissue Consortium (NNTC, which consists of samples from 3 different brain regions, including white matter, basal ganglia and frontal cortex of HIV-infected and control patients. While HIVE is characterized by widespread, uncontrolled inflammation and tissue damage, substantial gene expression evidence of induction of interferon (IFN, cytokines and tissue injury is apparent in all brain regions studied, even in the absence of NCI. Various degrees of white matter changes were present in all HIV-infected subjects and were the primary manifestation in patients with NCI in the absence of HIVE. In particular, NCI in patients without HIVE in the NNTC sample is associated with white matter expression of chemokines, cytokines and β-defensins, without significant activation of IFN. Altogether, the results identified distinct pathways differentially regulated over the course of neurological disease in HIV infection and provide a new perspective on the dynamics of pathogenic processes in the course of HIV neurological disease in humans. These results also demonstrate the power of the systems biology analyses and indicate that the establishment of larger human gene expression profile datasets will have the potential to provide novel mechanistic insight into the pathogenesis of neurological disease in HIV
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DEFF Research Database (Denmark)
Rovsing, Louise; Rath, Martin Fredensborg; Møller, Morten
2013-01-01
circadian AVP-rhythm. We have in this study of the brown 129sv mouse and the visual blind cone-rod homeobox gene knock out mouse (Crx(-/-) ) with degeneration of the retinal rods and cones, but a preserved non-image forming optic system, studied the temporal Avp-expression in both the neurosecretory...
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Low-cost computer mouse for the elderly or disabled in Taiwan.
Chen, C-C; Chen, W-L; Chen, B-N; Shih, Y-Y; Lai, J-S; Chen, Y-L
2014-01-01
A mouse is an important communication interface between a human and a computer, but it is still difficult to use for the elderly or disabled. To develop a low-cost computer mouse auxiliary tool. The principal structure of the low-cost mouse auxiliary tool is the IR (infrared ray) array module and the Wii icon sensor module, which combine with reflective tape and the SQL Server database. This has several benefits including cheap hardware cost, fluent control, prompt response, adaptive adjustment and portability. Also, it carries the game module with the function of training and evaluation; to the trainee, it is really helpful to upgrade the sensitivity of consciousness/sense and the centralization of attention. The intervention phase/maintenance phase, with regard to clicking accuracy and use of time, p value (p< 0.05) reach the level of significance. The development of the low cost adaptive computer mouse auxiliary tool was completed during the study and was also verified as having the characteristics of low cost, easy operation and the adaptability. To patients with physical disabilities, if they have independent control action parts of their limbs, the mouse auxiliary tool is suitable for them to use, i.e. the user only needs to paste the reflective tape by the independent control action parts of the body to operate the mouse auxiliary tool.
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Perineuronal nets play a role in regulating striatal function in the mouse.
Directory of Open Access Journals (Sweden)
Hyunchul Lee
Full Text Available The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs, aggregations of chondroitin-sulfate proteoglycans (CSPGs, form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41% of these structures surrounds parvalbumin positive (PV+ interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.
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Perineuronal nets play a role in regulating striatal function in the mouse.
Lee, Hyunchul; Leamey, Catherine A; Sawatari, Atomu
2012-01-01
The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs), aggregations of chondroitin-sulfate proteoglycans (CSPGs), form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41%) of these structures surrounds parvalbumin positive (PV+) interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.
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Olfaction in three genetic and two MPTP-induced Parkinson's disease mouse models.
Directory of Open Access Journals (Sweden)
Stefan Kurtenbach
Full Text Available Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three genetic Parkinson's disease (PD mouse models and mice treated with MPTP intraperitoneally and intranasally. To investigate olfactory function, we performed electro-olfactogram recordings (EOGs and an olfactory behavior test (cookie-finding test. We show that neither a parkin knockout mouse strain, nor intraperitoneal MPTP treated animals display any olfactory impairment in EOG recordings and the applied behavior test. We also found no difference in the responses of the olfactory epithelium to odorants in a mouse strain over-expressing doubly mutated α-synuclein, while this mouse strain was not suitable to test olfaction in a cookie-finding test as it displays a mobility impairment. A transgenic mouse expressing mutated α-synuclein in dopaminergic neurons performed equal to control animals in the cookie-finding test. Further we show that intranasal MPTP application can cause functional damage of the olfactory epithelium.
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Development of the mouse cochlea database (MCD).
Santi, Peter A; Rapson, Ian; Voie, Arne
2008-09-01
The mouse cochlea database (MCD) provides an interactive, image database of the mouse cochlea for learning its anatomy and data mining of its resources. The MCD website is hosted on a centrally maintained, high-speed server at the following URL: (http://mousecochlea.umn.edu). The MCD contains two types of image resources, serial 2D image stacks and 3D reconstructions of cochlear structures. Complete image stacks of the cochlea from two different mouse strains were obtained using orthogonal plane fluorescence optical microscopy (OPFOS). 2D images of the cochlea are presented on the MCD website as: viewable images within a stack, 2D atlas of the cochlea, orthogonal sections, and direct volume renderings combined with isosurface reconstructions. In order to assess cochlear structures quantitatively, "true" cross-sections of the scala media along the length of the basilar membrane were generated by virtual resectioning of a cochlea orthogonal to a cochlear structure, such as the centroid of the basilar membrane or the scala media. 3D images are presented on the MCD website as: direct volume renderings, movies, interactive QuickTime VRs, flythrough, and isosurface 3D reconstructions of different cochlear structures. 3D computer models can also be used for solid model fabrication by rapid prototyping and models from different cochleas can be combined to produce an average 3D model. The MCD is the first comprehensive image resource on the mouse cochlea and is a new paradigm for understanding the anatomy of the cochlea, and establishing morphometric parameters of cochlear structures in normal and mutant mice.
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Generation of Knock-in Mouse by Genome Editing.
Fujii, Wataru
2017-01-01
Knock-in mice are useful for evaluating endogenous gene expressions and functions in vivo. Instead of the conventional gene-targeting method using embryonic stem cells, an exogenous DNA sequence can be inserted into the target locus in the zygote using genome editing technology. In this chapter, I describe the generation of epitope-tagged mice using engineered endonuclease and single-stranded oligodeoxynucleotide through the mouse zygote as an example of how to generate a knock-in mouse by genome editing.
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Understanding Cancer Prognosis
Full Text Available ... NCI NCI Overview History Contributing to Cancer Research Leadership Director's Page Deputy Director's Page Previous NCI Directors ... History of NCI Contributing to Cancer Research Senior Leadership Director Deputy Director Previous Directors NCI Organization Divisions, ...
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Understanding Cancer Prognosis
Full Text Available ... Previous NCI Directors NCI Organization Advisory Boards and Review Groups Budget & Appropriations About the Annual Plan & Budget Proposal NCI Congressional Justification NCI Budget Fact Book Careers at NCI Visitor Information Legislative Activities Hearings & Testimonies ...
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Expression of HSG is essential for mouse blastocyst formation
International Nuclear Information System (INIS)
Jiang Guangjian; Pan Lei; Huang Xiuying; Han Mei; Wen Jinkun; Sun Fangzhen
2005-01-01
It has been shown recently that hyperplasia suppressor gene (HSG) is a powerful regulator for cell proliferation and has a critical role in mitochondrial fusion in many cells. However, little is known about its expression, localization, and function during oocyte maturation and early embryogenesis. In this study, with indirect immunofluorescent staining and Western blotting, we found that HSG was expressed in mouse oocytes and preimplantation embryos which primarily exhibited a submembrane distribution pattern in the cytoplasm. Moreover, HSG mainly associated with β-tubulin during oocyte maturation and early embryonic development. When mouse zygotes were injected with HSG antisense plasmid and cultured in vitro, their capacity to form blastocysts was severely impaired. Our results indicate that HSG plays an essential role in mouse preimplantation development
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Genome-wide identification of estrogen receptor alpha-binding sites in mouse liver
DEFF Research Database (Denmark)
Gao, Hui; Fält, Susann; Sandelin, Albin
2007-01-01
We report the genome-wide identification of estrogen receptor alpha (ERalpha)-binding regions in mouse liver using a combination of chromatin immunoprecipitation and tiled microarrays that cover all nonrepetitive sequences in the mouse genome. This analysis identified 5568 ERalpha-binding regions...... genes. The majority of ERalpha-binding regions lie in regions that are evolutionarily conserved between human and mouse. Motif-finding algorithms identified the estrogen response element, and variants thereof, together with binding sites for activator protein 1, basic-helix-loop-helix proteins, ETS...... signaling in mouse liver, by characterizing the first step in this signaling cascade, the binding of ERalpha to DNA in intact chromatin....
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New Insights on the Morphology of Adult Mouse Penis1
Rodriguez, Esequiel; Weiss, Dana A.; Yang, Jennifer H.; Menshenina, Julia; Ferretti, Max; Cunha, Tristan J.; Barcellos, Dale; Chan, Lok Yun; Risbridger, Gail; Cunha, Gerald R.; Baskin, Laurence S.
2011-01-01
ABSTRACT The adult mouse penis represents the end point of masculine sex differentiation of the embryonic genital tubercle and contains bone, cartilage, the urethra, erectile bodies, several types of epithelium, and many individual cell types arrayed into specific anatomical structures. Using contemporary high-resolution imaging techniques, we sought to provide new insights to the current description of adult mouse penile morphology to enable understanding of penile abnormalities, including hypospadias. Examination of serial transverse and longitudinal sections, scanning electron microscopy, and three-dimensional (3D) reconstruction provided a new appreciation of the individual structures in the adult mouse penis and their 3D interrelationships. In so doing, we discovered novel paired erectile bodies, the male urogenital mating protuberance (MUMP), and more accurately described the urethral meatus. These morphological observations were quantified by morphometric analysis and now provide accurate morphological end points of sex differentiation of mouse penis that will be the foundation of future studies to identify normal and abnormal penile development. PMID:21918128
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Krais, Annette M.; Mühlbauer, Karl-Rudolf; Kucab, Jill E.; Chinbuah, Helena; Cornelius, Michael G.; Wei, Quan-Xiang; Hollstein, Monica; Phillips, David H.; Arlt, Volker M.; Schmeiser, Heinz H.
2015-01-01
We compared mouse embryonic stem (ES) cells and fibroblasts (MEFs) for their ability to metabolically activate the environmental carcinogens benzo[a]pyrene (BaP), 3-nitrobenzanthrone (3-NBA) and aristolochic acid I (AAI), measuring DNA adduct formation by 32P-postlabelling and expression of xenobiotic-metabolism genes by quantitative real-time PCR. At 2 μM, BaP induced Cyp1a1 expression in MEFs to a much greater extent than in ES cells and formed 45 times more adducts. Nqo1 mRNA expression was increased by 3-NBA in both cell types but induction was higher in MEFs, as was adduct formation. For AAI, DNA binding was over 450 times higher in MEFs than in ES cells, although Nqo1 and Cyp1a1 transcriptional levels did not explain this difference. We found higher global methylation of DNA in ES cells than in MEFs, which suggests higher chromatin density and lower accessibility of the DNA to DNA damaging agents in ES cells. However, AAI treatment did not alter DNA methylation. Thus mouse ES cells and MEFs have the metabolic competence to activate a number of environmental carcinogens, but MEFs have lower global DNA methylation and higher metabolic capacity than mouse ES cells. PMID:25230394
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2011-10-07
...; Comment Request; A Generic Submission for Theory Development and Validation (NCI) SUMMARY: Under the... control number. Proposed Collection: Title: A Generic Submission for Theory Development and Validation...), to conduct and support behavioral research informed by and informing theory. Formative research in...
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Su, Cheng-Kuan; Tseng, Po-Jen; Chiu, Hsien-Ting; Del Vall, Andrea; Huang, Yu-Fen; Sun, Yuh-Chang
2017-03-01
Probing tumor extracellular metabolites is a vitally important issue in current cancer biology. In this study an analytical system was constructed for the in vivo monitoring of mouse tumor extracellular hydrogen peroxide (H 2 O 2 ), lactate, and glucose by means of microdialysis (MD) sampling and fluorescence determination in conjunction with a smart sequential enzymatic derivatization scheme-involving a loading sequence of fluorogenic reagent/horseradish peroxidase, microdialysate, lactate oxidase, pyruvate, and glucose oxidase-for step-by-step determination of sampled H 2 O 2 , lactate, and glucose in mouse tumor microdialysate. After optimization of the overall experimental parameters, the system's detection limit reached as low as 0.002 mM for H 2 O 2 , 0.058 mM for lactate, and 0.055 mM for glucose, based on 3 μL of microdialysate, suggesting great potential for determining tumor extracellular concentrations of lactate and glucose. Spike analyses of offline-collected mouse tumor microdialysate and monitoring of the basal concentrations of mouse tumor extracellular H 2 O 2 , lactate, and glucose, as well as those after imparting metabolic disturbance through intra-tumor administration of a glucose solution through a prior-implanted cannula, were conducted to demonstrate the system's applicability. Our results evidently indicate that hyphenation of an MD sampling device with an optimized sequential enzymatic derivatization scheme and a fluorescence spectrometer can be used successfully for multi-analyte monitoring of tumor extracellular metabolites in living animals. Copyright © 2016 Elsevier B.V. All rights reserved.
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Mouse cell culture - Methods and protocols
Directory of Open Access Journals (Sweden)
CarloAlberto Redi
2010-12-01
Full Text Available The mouse is, out of any doubt, the experimental animal par excellence for many many colleagues within the scientific community, notably for those working in mammalian biology (in a broad sense, from basic genetic to modeling human diseases, starting at least from 1664 Robert Hooke experiments on air’s propertyn. Not surprising then that mouse cell cultures is a well established field of research itself and that there are several handbooks devoted to this discipline. Here, Andrew Ward and David Tosh provide a necessary update of the protocols currently needed. In fact, nearly half of the book is devoted to stem cells culture protocols, mainly embryonic, from a list of several organs (kidney, lung, oesophagus and intestine, pancreas and liver to mention some........
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Liu, Bo; Kruger, Robert; Reinecke, Daniel; Stantz, Keith M.
2010-02-01
Purpose: The purpose of this study is to use PCT spectroscopy scanner to monitor the hemoglobin concentration and oxygen saturation change of living mouse by imaging the artery and veins in a mouse tail. Materials and Methods: One mouse tail was scanned using the PCT small animal scanner at the isosbestic wavelength (796nm) to obtain its hemoglobin concentration. Immediately after the scan, the mouse was euthanized and its blood was extracted from the heart. The true hemoglobin concentration was measured using a co-oximeter. Reconstruction correction algorithm to compensate the acoustic signal loss due to the existence of bone structure in the mouse tail was developed. After the correction, the hemoglobin concentration was calculated from the PCT images and compared with co-oximeter result. Next, one mouse were immobilized in the PCT scanner. Gas with different concentrations of oxygen was given to mouse to change the oxygen saturation. PCT tail vessel spectroscopy scans were performed 15 minutes after the introduction of gas. The oxygen saturation values were then calculated to monitor the oxygen saturation change of mouse. Results: The systematic error for hemoglobin concentration measurement was less than 5% based on preliminary analysis. Same correction technique was used for oxygen saturation calculation. After correction, the oxygen saturation level change matches the oxygen volume ratio change of the introduced gas. Conclusion: This living mouse tail experiment has shown that NIR PCT-spectroscopy can be used to monitor the oxygen saturation status in living small animals.
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Mouse ribosomal RNA genes contain multiple differentially regulated variants.
Directory of Open Access Journals (Sweden)
Hung Tseng
2008-03-01
Full Text Available Previous cytogenetic studies suggest that various rDNA chromosomal loci are not equally active in different cell types. Consistent with this variability, rDNA polymorphism is well documented in human and mouse. However, attempts to identify molecularly rDNA variant types, which are regulated individually (i.e., independent of other rDNA variants and tissue-specifically, have not been successful. We report here the molecular cloning and characterization of seven mouse rDNA variants (v-rDNA. The identification of these v-rDNAs was based on restriction fragment length polymorphisms (RFLPs, which are conserved among individuals and mouse strains. The total copy number of the identified variants is less than 100 and the copy number of each individual variant ranges from 4 to 15. Sequence analysis of the cloned v-rDNA identified variant-specific single nucleotide polymorphisms (SNPs in the transcribed region. These SNPs were used to develop a set of variant-specific PCR assays, which permitted analysis of the v-rDNAs' expression profiles in various tissues. These profiles show that three v-rDNAs are expressed in all tissues (constitutively active, two are expressed in some tissues (selectively active, and two are not expressed (silent. These expression profiles were observed in six individuals from three mouse strains, suggesting the pattern is not randomly determined. Thus, the mouse rDNA array likely consists of genetically distinct variants, and some are regulated tissue-specifically. Our results provide the first molecular evidence for cell-type-specific regulation of a subset of rDNA.
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Zinc-enriched (ZEN) terminals in mouse spinal cord
DEFF Research Database (Denmark)
Jo, S M; Danscher, G; Schrøder, H D
2000-01-01
The general distribution of zinc-enriched (ZEN) terminals in mouse spinal cord was investigated at light microscopic level by means of zinc transporter-3 immunohistochemistry (ZnT3(IHC)) and zinc selenium autometallography (ZnSe(AMG)). Staining for ZnT3(IHC) corresponded closely to the Zn...... dendrites. These ZEN terminals in the ventral horn were in general larger than those in the dorsal horn. This is the first description of the pattern of ZEN terminals in mouse spinal cord....
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Cryo-imaging of fluorescently labeled single cells in a mouse
Steyer, Grant J.; Roy, Debashish; Salvado, Olivier; Stone, Meredith E.; Wilson, David L.
2009-02-01
We developed a cryo-imaging system to provide single-cell detection of fluorescently labeled cells in mouse, with particular applicability to stem cells and metastatic cancer. The Case cryoimaging system consists of a fluorescence microscope, robotic imaging positioner, customized cryostat, PC-based control system, and visualization/analysis software. The system alternates between sectioning (10-40 μm) and imaging, collecting color brightfield and fluorescent blockface image volumes >60GB. In mouse experiments, we imaged quantum-dot labeled stem cells, GFP-labeled cancer and stem cells, and cell-size fluorescent microspheres. To remove subsurface fluorescence, we used a simplified model of light-tissue interaction whereby the next image was scaled, blurred, and subtracted from the current image. We estimated scaling and blurring parameters by minimizing entropy of subtracted images. Tissue specific attenuation parameters were found [uT : heart (267 +/- 47.6 μm), liver (218 +/- 27.1 μm), brain (161 +/- 27.4 μm)] to be within the range of estimates in the literature. "Next image" processing removed subsurface fluorescence equally well across multiple tissues (brain, kidney, liver, adipose tissue, etc.), and analysis of 200 microsphere images in the brain gave 97+/-2% reduction of subsurface fluorescence. Fluorescent signals were determined to arise from single cells based upon geometric and integrated intensity measurements. Next image processing greatly improved axial resolution, enabled high quality 3D volume renderings, and improved enumeration of single cells with connected component analysis by up to 24%. Analysis of image volumes identified metastatic cancer sites, found homing of stem cells to injury sites, and showed microsphere distribution correlated with blood flow patterns. We developed and evaluated cryo-imaging to provide single-cell detection of fluorescently labeled cells in mouse. Our cryo-imaging system provides extreme (>60GB), micron
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Directory of Open Access Journals (Sweden)
bahram amuoghlitabrizi
2013-11-01
Full Text Available Infertility is a complicated problem with medical significance. Gingeras amedicinalherb is used to treata number of diseasessuch assexualweakness. The aim of this study was to evaluate the effects of ginger rhizome extract on heat-induced testicular damage in the mouse. Fourtymale mice were randomly divided into 4 equal groups including: 1- Control, 2- heat stressed, 3 and 4- stressed and treated with ginger extract (1/5 and 3 mg/animal/day. The scrotum of experimental mice was immersed for 20 min in a water bath at 42°C. Control mice were similarly treated except that the water bath was maintained at 23°C. Mice were euthanized after 50 days. Blood samples were collected for analysis of testosterone levels. Testes were removed for histopathological assessment and oxidant/antioxidant status. Heat stress significantly reduced blood testosterone level and increased lipid peroxidation product and decreased antioxidant activities of superoxide dismutase, catalase and glutathione peroxidase (p
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Moody, Terry W; Switzer, Christopher; Santana-Flores, Wilmarie; Ridnour, Lisa A; Berna, Marc; Thill, Michelle; Jensen, Robert T; Sparatore, Anna; Del Soldato, Piero; Yeh, Grace C; Roberts, David D; Giaccone, Giuseppe; Wink, David A
2010-05-01
The effects of dithiolethione modified valproate, diclofenac and sulindac on non-small cell lung cancer (NSCLC) cells were investigated. Sulfur(S)-valproate and S-diclofenac at 1 microg/ml concentrations significantly reduced prostaglandin (PG)E(2) levels in NSCLC cell lines A549 and NCI-H1299 as did the COX-2 inhibitor DuP-697. In vitro, S-valproate, S-diclofenac and S-sulindac half-maximally inhibited the clonal growth of NCI-H1299 cells at 6, 6 and 15 microg/ml, respectively. Using the MTT assay, 10 microg/ml S-valproate, NO-aspirin and Cay10404, a selective COX-2 inhibitor, but not SC-560, a selective COX-1 inhibitor, inhibited the growth of A549 cells. In vivo, 18mg/kg i.p. of S-valproate and S-diclofenac, but not S-sulindac, significantly inhibited A549 or NCI-H1299 xenograft proliferation in nude mice, but had no effect on the nude mouse body weight. The mechanism by which S-valproate and S-diclofenac inhibited the growth of NSCLC cells was investigated. Nitric oxide-aspirin but not S-valproate caused apoptosis of NSCLC cells. By Western blot, S-valproate and S-diclofenac increased E-cadherin but reduced vimentin and ZEB1 (a transcriptional suppressor of E-cadherin) protein expression in NSCLC cells. Because S-valproate and S-diclofenac inhibit the growth of NSCLC cells and reduce PGE(2) levels, they may prove beneficial in the chemoprevention and/or therapy of NSCLC. Published by Elsevier Ireland Ltd.
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2010-12-17
... participant in depth about interpretations of questions, recall processes used to answer them, and adequacy of... no costs to respondents other than their time. The total estimated annualized burden hours are 600...) Pilot 1,200 1 30/60 (0.5) 600.0 Household interviews. Totals 3,600 3,600.0 The estimated total annual...
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Isolation and characterization of proteins of the mouse mammary tumour virus
International Nuclear Information System (INIS)
Westenbrink, F.
1980-01-01
A vaccination procedure was developed to mouse mammary tumor virus (MuMTV) induced mouse mammary tumorigenesis. The structural proteins of MuMTV were purified so that their immunogenic qualities were retained. Radioimmunoassays were developed for the proteins. (Auth.)
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Activation of farnesoid X receptor induces RECK expression in mouse liver
International Nuclear Information System (INIS)
Peng, Xiaomin; Wu, Weibin; Zhu, Bo; Sun, Zhichao; Ji, Lingling; Ruan, Yuanyuan; Zhou, Meiling; Zhou, Lei; Gu, Jianxin
2014-01-01
Highlights: •RECK is a novel transcriptional target gene of FXR in mouse liver. •The FXR response element is located within the intron 1 of RECK gene. •FXR agonist reverses the down-regulation of RECK in the liver in mouse NASH model. -- Abstract: Farnesoid X receptor (FXR) belongs to the ligand-activated nuclear receptor superfamily, and functions as a transcription factor regulating the transcription of numerous genes involved in bile acid homeostasis, lipoprotein and glucose metabolism. In the present study, we identified RECK, a membrane-anchored inhibitor of matrix metalloproteinases, as a novel target gene of FXR in mouse liver. We found that FXR agonist substantially augmented hepatic RECK mRNA and protein expression in vivo and in vitro. FXR regulated the transcription of RECK through directly binding to FXR response element located within intron 1 of the mouse RECK gene. Moreover, FXR agonist reversed the down-regulation of RECK in the livers from mice fed a methionine and choline deficient diet. In summary, our data suggest that RECK is a novel transcriptional target of FXR in mouse liver, and provide clues to better understanding the function of FXR in liver
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Activation of farnesoid X receptor induces RECK expression in mouse liver
Energy Technology Data Exchange (ETDEWEB)
Peng, Xiaomin [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Wu, Weibin [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Sciences, Fudan University, Shanghai 200032 (China); Zhu, Bo; Sun, Zhichao; Ji, Lingling; Ruan, Yuanyuan [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Zhou, Meiling, E-mail: meilingzhou2012@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Zhou, Lei, E-mail: yhchloech@gmail.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Sciences, Fudan University, Shanghai 200032 (China)
2014-01-03
Highlights: •RECK is a novel transcriptional target gene of FXR in mouse liver. •The FXR response element is located within the intron 1 of RECK gene. •FXR agonist reverses the down-regulation of RECK in the liver in mouse NASH model. -- Abstract: Farnesoid X receptor (FXR) belongs to the ligand-activated nuclear receptor superfamily, and functions as a transcription factor regulating the transcription of numerous genes involved in bile acid homeostasis, lipoprotein and glucose metabolism. In the present study, we identified RECK, a membrane-anchored inhibitor of matrix metalloproteinases, as a novel target gene of FXR in mouse liver. We found that FXR agonist substantially augmented hepatic RECK mRNA and protein expression in vivo and in vitro. FXR regulated the transcription of RECK through directly binding to FXR response element located within intron 1 of the mouse RECK gene. Moreover, FXR agonist reversed the down-regulation of RECK in the livers from mice fed a methionine and choline deficient diet. In summary, our data suggest that RECK is a novel transcriptional target of FXR in mouse liver, and provide clues to better understanding the function of FXR in liver.
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Biology and genomics of an historic therapeutic Escherichia coli bacteriophage collection
DEFF Research Database (Denmark)
Baig, Abiyad; Colom, Joan; Barrow, Paul
2017-01-01
We have performed microbiological and genomic characterization of an historic collection of nine bacteriophages, specifically infecting a K1 E. coli O18:K1:H7 ColV+ strain. These phages were isolated from sewage and tested for their efficacy in vivo for the treatment of systemic E. coli infection...... in a mouse infection model by Smith and Huggins (1982). The aim of the study was to identify common microbiological and genomic characteristics, which co-relate to the performance of these phages in in vivo study. These features will allow an informed selection of phages for use as therapeutic agents...
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Formation of DNA adducts in mouse tissues after 1-nitropyrene administration
International Nuclear Information System (INIS)
Mitchell, C.E.
1986-01-01
DNA adducts were isolated and characterized in mouse lung, liver and kidney after intratracheal instillation of [ 3 H]-1-nitropyrene (1-NP). HPLC analysis of the enzymatically digested DNA indicated the presence of multiple DNA adducts in mouse lung, liver and kidney. These results indicate that DNA adducts of 1-NP are formed in mouse lung, liver and kidney after intratracheal instillation of 1-NP; the HPLC profiles of the multiple adducts suggests that adducts may be formed via metabolic pathways that involve both nitroreduction and ring-oxidation. 6 references, 1 figure
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Spatial integration in mouse primary visual cortex.
Vaiceliunaite, Agne; Erisken, Sinem; Franzen, Florian; Katzner, Steffen; Busse, Laura
2013-08-01
Responses of many neurons in primary visual cortex (V1) are suppressed by stimuli exceeding the classical receptive field (RF), an important property that might underlie the computation of visual saliency. Traditionally, it has proven difficult to disentangle the underlying neural circuits, including feedforward, horizontal intracortical, and feedback connectivity. Since circuit-level analysis is particularly feasible in the mouse, we asked whether neural signatures of spatial integration in mouse V1 are similar to those of higher-order mammals and investigated the role of parvalbumin-expressing (PV+) inhibitory interneurons. Analogous to what is known from primates and carnivores, we demonstrate that, in awake mice, surround suppression is present in the majority of V1 neurons and is strongest in superficial cortical layers. Anesthesia with isoflurane-urethane, however, profoundly affects spatial integration: it reduces the laminar dependency, decreases overall suppression strength, and alters the temporal dynamics of responses. We show that these effects of brain state can be parsimoniously explained by assuming that anesthesia affects contrast normalization. Hence, the full impact of suppressive influences in mouse V1 cannot be studied under anesthesia with isoflurane-urethane. To assess the neural circuits of spatial integration, we targeted PV+ interneurons using optogenetics. Optogenetic depolarization of PV+ interneurons was associated with increased RF size and decreased suppression in the recorded population, similar to effects of lowering stimulus contrast, suggesting that PV+ interneurons contribute to spatial integration by affecting overall stimulus drive. We conclude that the mouse is a promising model for circuit-level mechanisms of spatial integration, which relies on the combined activity of different types of inhibitory interneurons.
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Choi, Seon Young; Kim, Hang-Rae; Ryu, Pan Dong; Lee, So Yeong
2017-02-21
Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux. In the present study, we found that mRNA expression of Kv channels in SP cells was different compared to Non-SP cells, and the resistance of SP cells to gefitinib was weakened with a combination treatment of gefitinib and Kv channel blockers or a Kv7 opener, compared to single-treatment gefitinib, through inhibition of the Ras-Raf signaling pathway. The findings indicate that Kv channels in SP cells could be new targets for reducing the resistance to gefitinib.
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Isolation, culture and adenoviral transduction of parietal cells from mouse gastric mucosa
International Nuclear Information System (INIS)
Gliddon, Briony L; Nguyen, Nhung V; Gunn, Priscilla A; Gleeson, Paul A; Driel, Ian R van
2008-01-01
Here we describe a method for the isolation of intact gastric glands from mice and primary culture and transfection of mouse gastric epithelial cells. Collagenase digestion of PBS-perfused mouse stomachs released large intact gastric glands that were plated on a basement membrane matrix. The heterogeneous gland cell cultures typically contain ∼60% parietal cells. Isolated mouse parietal cells remain viable in culture for up to 5 days and react strongly with an antibody specific to the gastric H + /K + ATPase. Isolated intact mouse gastric glands and primary cultures of mouse parietal cells respond to the secretagogue, histamine. Typical morphological changes from a resting to an acid-secreting active parietal cell were observed. In resting cultures of mouse parietal cells, the H + /K + ATPase displayed a cytoplasmic punctate staining pattern consistent with tubulovesicle element structures. Following histamine stimulation, an expansion of internal apical vacuole structures was observed together with a pronounced redistribution of the H + /K + ATPase from the cytoplasm to the apical vacuoles. A reproducible procedure to express genes of interest exogenously in these cultures of mouse parietal cells was also established. This method combines recombinant adenoviral transduction with magnetic field-assisted transfection resulting in ∼30% transduced parietal cells. Adenoviral-transduced parietal cells maintain their ability to undergo agonist-induced activation. This protocol will be useful for the isolation, culture and expression of genes in parietal cells from genetically modified mice and as such will be an invaluable tool for studying the complex exocytic and endocytic trafficking events of the H + /K + ATPase which underpin the regulation of acid secretion
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Lei, D; Lin, Y; Jiang, X; Lan, L; Zhang, W; Wang, B X
2017-03-02
Objective: To explore the composition of the gastrointestinal bacterial flora of mouse embryos and the placenta tissue bacterial flora. Method: Twenty-four specimens were collected from pregnant Kunming mouse including 8 mice of early embryonic (12-13 days) gastrointestinal tissues, 8 cases of late embryonic (19-20 days)gastrointestinal tissues, 8 of late pregnancy placental tissues.The 24 samples were extracted by DNeasy Blood & Tissue kit for high-throughput DNA sequencing. Result: The level of Proteobacteria, Bacteroidetes, Actino-bacteria and Firmicutes were predominantin all specimens.The relative content of predominant bacterial phyla in each group: Proteobacteria (95.00%, 88.14%, 87.26%), Bacteroidetes(1.71%, 2.15%, 2.63%), Actino-Bacteria(1.16%, 4.10%, 3.38%), Firmicutes(0.75%, 2.62%, 2.01%). At the level of family, there were nine predominant bacterial families in which Enterobacteriaeae , Shewanel laceae and Moraxellaceae were dominant.The relative content of dominant bacterial family in eachgroup: Enterobacteriaeae (46.99%, 44.34%, 41.08%), Shewanellaceae (21.99%, 21.10%, 19.05%), Moraxellaceae (9.18%, 7.09%, 5.64%). From the species of flora, the flora from fetal gastrointestinal in early pregnancy and late pregnancy (65.44% and 62.73%) were the same as that from placenta tissue in the late pregnancy.From the abundance of bacteria, at the level of family, the same content of bacteria in three groups accounted for 78.16%, 72.53% and 65.78% respectively. Conclusion: It was proved that the gastrointestinal bacterial flora of mouse embryos and the placenta tissue bacterial flora were colonized. At the same time the bacteria are classified.
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A cytocidal tissue kallikrein isolated from mouse submandibular glands.
Murakami, K; Ikigai, H; Nagumo, N; Tomita, M; Shimamura, T
1989-11-06
A cytocidal factor against mouse thymocytes was purified from the submandibular glands of female BALB/c mice using Sephadex G-50 gel filtration chromatography and reverse-phase HPLC. SDS-PAGE and amino acid sequence analysis revealed that the cytocidal factor was mouse glandular kallikrein (mGK)-6. mGK-6 showed an optimal enzyme activity at pH 10 and a cytocidal activity against thymocytes in a dose-dependent manner.
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2011-03-02
... submissions. There are no Capital Costs, Operating Costs, and/or Maintenance Costs to report. [[Page 11499... Transfer Center (TTC) External Customer Satisfaction Surveys (NCI). Type of Information Collection Request.... Affected Public: Private Sector. Type of Respondents: Managers, Executives and Directors from Foundations...
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IT Department
2011-01-01
“Stop --- Think --- Click" is the basic recommendation for securely browsing the Internet and for securely reading e-mails. Users who have followed this recommendation in the past were less likely to have their computer infected or their computing account compromised. We would like to thank all those who donated their mouse to the CERN Animal Shelter for Computer Mice (http://cern.ch/c-a-s). For those who still use a mouse, please stay vigilant and alert: do not click on links whose origin you do not trust or which look like gibberish. Do not install untrusted software or plug-ins, since software from untrusted sources may infect or compromise your computer, or violate copyrights. Finally, take particular care with e-mails: Do not open unexpected or suspicious e-mails or attachments. Delete them if they do not concern you or if they appear strange. If in doubt, or if you have questions, please do not hesitate to contact Computer.Security@cern.ch
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Swede, Helen; Sarwar, Amna; Magge, Anil; Braithwaite, Dejana; Cook, Linda S; Gregorio, David I; Jones, Beth A; R Hoag, Jessica; Gonsalves, Lou; L Salner, Andrew; Zarfos, Kristen; Andemariam, Biree; Stevens, Richard G; G Dugan, Alicia; Pensa, Mellisa; A Brockmeyer, Jessica
2016-05-01
A comparatively high prevalence of comorbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at threefold the rate in AA/B compared to white breast cancer patients. We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000-2007. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox survival analyses estimated hazard ratios (HRs) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors. Among patients with SEER local stage, TNBC increased the risk of death (HR 2.18, 95 % CI 1.14-4.16), which was attenuated when the CCI score was added to the model (Adj. HR 1.50, 95 % CI 0.74-3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR 1.49, 95 % CI 1.29-1.71; per one point increase). Similar patterns were observed in SEER regional stage, but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR 5.65, 95 % CI 2.90-11.02). A lower and nonsignificant effect was observed for whites with a CCI of ≥3 (Adj. HR 1.90, 95 % CI 0.68-5.29). comorbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk.
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Wiktorowicz, Tatiana; Kinter, Jochen; Kobuke, Kazuhiro; Campbell, Kevin P; Sinnreich, Michael
2015-01-01
Mouse models of dysferlinopathies are valuable tools with which to investigate the pathomechanisms underlying these diseases and to test novel therapeutic strategies. One such mouse model is the Dysf (tm1Kcam) strain, which was generated using a targeting vector to replace a 12-kb region of the dysferlin gene and which features a progressive muscular dystrophy. A prerequisite for successful animal studies using genetic mouse models is an accurate genotyping protocol. Unfortunately, the lack of robustness of currently available genotyping protocols for the Dysf (tm1Kcam) mouse has prevented efficient colony management. Initial attempts to improve the genotyping protocol based on the published genomic structure failed. These difficulties led us to analyze the targeted locus of the dysferlin gene of the Dysf (tm1Kcam) mouse in greater detail. In this study we resequenced and analyzed the targeted locus of the Dysf (tm1Kcam) mouse and developed a novel PCR protocol for genotyping. We found that instead of a deletion, the dysferlin locus in the Dysf (tm1Kcam) mouse carries a targeted insertion. This genetic characterization enabled us to establish a reliable method for genotyping of the Dysf (tm1Kcam) mouse, and thus has made efficient colony management possible. Our work will make the Dysf (tm1Kcam) mouse model more attractive for animal studies of dysferlinopathies.
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Németh, Balázs Csaba; Wartmann, Thomas; Halangk, Walter; Sahin-Tóth, Miklós
2013-08-16
Chymotrypsin C (CTRC) is a proteolytic regulator of trypsinogen autoactivation in humans. CTRC cleavage of the trypsinogen activation peptide stimulates autoactivation, whereas cleavage of the calcium binding loop promotes trypsinogen degradation. Trypsinogen mutations that alter these regulatory cleavages lead to increased intrapancreatic trypsinogen activation and cause hereditary pancreatitis. The aim of this study was to characterize the regulation of autoactivation of mouse trypsinogens by mouse Ctrc. We found that the mouse pancreas expresses four trypsinogen isoforms to high levels, T7, T8, T9, and T20. Only the T7 activation peptide was cleaved by mouse Ctrc, causing negligible stimulation of autoactivation. Surprisingly, mouse Ctrc poorly cleaved the calcium binding loop in all mouse trypsinogens. In contrast, mouse Ctrc readily cleaved the Phe-150-Gly-151 peptide bond in the autolysis loop of T8 and T9 and inhibited autoactivation. Mouse chymotrypsin B also cleaved the same peptide bond but was 7-fold slower. T7 was less sensitive to chymotryptic regulation, which involved slow cleavage of the Leu-149-Ser-150 peptide bond in the autolysis loop. Modeling indicated steric proximity of the autolysis loop and the activation peptide in trypsinogen, suggesting the cleaved autolysis loop may directly interfere with activation. We conclude that autoactivation of mouse trypsinogens is under the control of mouse Ctrc with some notable differences from the human situation. Thus, cleavage of the trypsinogen activation peptide or the calcium binding loop by Ctrc is unimportant. Instead, inhibition of autoactivation via cleavage of the autolysis loop is the dominant mechanism that can mitigate intrapancreatic trypsinogen activation.
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Wireless data collection of self-administered surveys using tablet computers.
Singleton, Kyle W; Lan, Mars; Arnold, Corey; Vahidi, Mani; Arangua, Lisa; Gelberg, Lillian; Bui, Alex A T
2011-01-01
The accurate and expeditious collection of survey data by coordinators in the field is critical in the support of research studies. Early methods that used paper documentation have slowly evolved into electronic capture systems. Indeed, tools such as REDCap and others illustrate this transition. However, many current systems are tailored web-browsers running on desktop/laptop computers, requiring keyboard and mouse input. We present a system that utilizes a touch screen interface running on a tablet PC with consideration for portability, limited screen space, wireless connectivity, and potentially inexperienced and low literacy users. The system was developed using C#, ASP.net, and SQL Server by multiple programmers over the course of a year. The system was developed in coordination with UCLA Family Medicine and is currently deployed for the collection of data in a group of Los Angeles area clinics of community health centers for a study on drug addiction and intervention.
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Fujii, Takashi; Ikeda, Katsumi; Saito, Morio
2011-01-01
The compounds present in rose hips exerting an inhibitory action against melanogenesis in B16 mouse melanoma cells were investigated by dividing an aqueous extract of rose hips (RE) into four fractions. The 50% ethanol eluate from a DIAION HP-20 column significantly reduced the production of melanin and was mainly composed of procyanidin glycosides. We also found that this 50% ethanol eluate reduced the intracellular tyrosinase activity and also had a direct inhibitory effect on tyrosinase obtained as a protein mixture from the melanoma cell lysate. We also investigated the effect of orally administering RE on skin pigmentation in brown guinea pigs, and found that the pigmentation was inhibited together with the tyrosinase activity in the skin. These data collectively suggest that proanthocyanidins from RE inhibited melanogenesis in mouse melanoma cells and guinea pig skin, and could be useful as a skin-whitening agent when taken orally.
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The Oak Ridge Polycystic Kidney mouse: modeling ciliopathies of mice and men.
Energy Technology Data Exchange (ETDEWEB)
Lehman, J M [University of Alabama, Birmingham; Michaud III, Edward J [ORNL; Schoeb, T [University of Alabama, Birmingham; Aydin Son, Yesim [University of Tennessee, Knoxville (UTK); Miller, M [University of Alabama, Birmingham; Yoder, Bradley [University of Alabama, Birmingham
2008-08-01
The Oak Ridge Polycystic Kidney (ORPK) mouse was described nearly 14 years ago as a model for human recessive polycystic kidney disease. The ORPK mouse arose through integration of a transgene into an intron of the Ift88 gene resulting in a hypomorphic allele (Ift88Tg737Rpw). The Ift88Tg737Rpw mutation impairs intraflagellar transport (IFT), a process required for assembly of motile and immotile cilia. Historically, the primary immotile cilium was thought to have minimal importance for human health; however, a rapidly expanding number of human disorders have now been attributed to ciliary defects. Importantly, many of these phenotypes are present and can be analyzed using the ORPK mouse. In this review, we highlight the research conducted using the OPRK mouse and the phenotypes shared with human cilia disorders. Furthermore, we describe an additional follicular dysplasia phenotype in the ORPK mouse, which alongside the ectodermal dysplasias seen in human Ellis-van Creveld and Sensenbrenner's syndromes, suggests an unappreciated role for primary cilia in the skin and hair follicle.
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Binding of mouse immunoglobulin G to polylysine-coated glass substrate for immunodiagnosis
Vashist, Sandeep Kumar; Tewari, Rupinder; Bajpai, Ram Prakash; Bharadwaj, Lalit Mohan; Raiteri, Roberto
2006-12-01
We report a method for immobilizing mouse immunoglobulin G (IgG) on polylysine-coated glass substrate for immunodiagnostic applications. Mouse IgG molecules were immobilized on polylysine-coated glass substrate employing 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and protein A. The amino groups of the polylysine-coated glass slide were cross linked to the carboxyl groups of protein A employing EDC crosslinker. Protein A was employed as it binds to the constant Fc region of antibodies keeping their antigen binding sites on the variable F ab region free to bind to antigens. The qualitative analysis of surface immobilized mouse IgG was done by fluorescent microscopy employing fluorescein isothiocyanate (FITC) labeled mouse IgG molecules. The immobilization densities of protein A and mouse IgG were determined by 3, 3', 4, 4'-tetramethyl benzidine (TMB) substrate assay employing horse radish peroxidise labelled molecules and were found to be 130 +/- 17 ng/cm2 and 596 +/- 31 ng/cm2 respectively. The biomolecular coatings analyzed by atomic force microscopy (AFM) were found to be uniform.
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Generation of Elf5-Cre knockin mouse strain for trophoblast-specific gene manipulation.
Kong, Shuangbo; Liang, Guixian; Tu, Zhaowei; Chen, Dunjin; Wang, Haibin; Lu, Jinhua
2018-04-01
Placental development is a complex and highly controlled process during which trophoblast stem cells differentiate to various trophoblast subtypes. The early embryonic death of systemic gene knockout models hampers the investigation of these genes that might play important roles during placentation. A trophoblast specific Cre mouse model would be of great help for dissecting out the potential roles of these genes during placental development. For this purpose, we generate a transgenic mouse with the Cre recombinase inserted into the endogenous locus of Elf5 gene that is expressed specifically in placental trophoblast cells. To analyze the specificity and efficiency of Cre recombinase activity in Elf5-Cre mice, we mated Elf5-Cre mice with Rosa26 mT/mG reporter mice, and found that Elf5-Cre transgene is expressed specifically in the trophoectoderm as early as embryonic day 4.5 (E4.5). By E12.5, the activity of Elf5-Cre transgene was detected exclusively in all derivatives of trophoblast lineages, including spongiotrophoblast, giant cells, and labyrinth trophoblasts. In addition, Elf5-Cre transgene was also active during spermatogenesis, from spermatids to mature sperms, which is consistent with the endogenous Elf5 expression in testis. Collectively, our results provide a unique tool to delete specific genes selectively and efficiently in trophoblast lineage during placentation. © 2018 Wiley Periodicals, Inc.
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Development of teeth in chick embryos after mouse neural crest transplantations.
Mitsiadis, Thimios A; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane
2003-05-27
Teeth were lost in birds 70-80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick chimeras obtained show evidence of tooth formation showing that avian oral epithelium is able to induce a nonavian developmental program in mouse neural crest-derived mesenchymal cells.
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Digital three-dimensional reconstruction and ultrastructure of the mouse proximal tubule
DEFF Research Database (Denmark)
Zhai, X.Y.; Birn, H.; Jensen, K.B.
2003-01-01
. In the medullary rays, these are arranged in layers outside the clusters of more superficial tubules. In contrast to rat and human kidney, no major segmental variation in the ultrastructure of the proximal tubule was identified, and no parameters enabled definition of distinct segments in this strain of mice......, detailed analyses of normal mouse kidney structure and organization are lacking. This study describes the 3D organization and ultrastructural, segmental variation of the mouse kidney proximal tubule. A total of 160 proximal tubules in three C57/BL/6J mouse kidneys were analyzed on 800 serial sections from...
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X-ray-induced chromosome aberrations in the leucocytes of mouse and man
International Nuclear Information System (INIS)
Preston, R.J.; Brewen, J.G.
1978-01-01
In earlier studies it was shown that the frequency of dicentrics induced by X-rays in human leucocytes was about twice that induced in mouse leucocytes. The frequencies of deletions were similar in both species. However, the mouse cultures were fixed at 60 h and the human cultures at 54 h. In both cases it was likely that some of the cells analysed were in their second post-treatment mitosis. Further studies were carried out using fixation times of 48 h for both mouse and human cultures (three different human donors were used). The same relationships held here, namely twice as many dicentrics in humans, and similar deletion frequencies in both. The aberration frequencies observed were corrected to take account of second-diversion cells by assuming that cells containing a dicentric without an accompanying fragment were in their second division. There were more such cells in mouse than in human cultures. Further to increase reliance on the conclusions, cultures were fixed at the earliest times that 300 cells per dose could be obtained - 36 h for the mouse, 42 h for the human. The frequencies of dicentrics were increased in both, and a relationship of about 2:1 for human to mouse was obtained. Deletion frequencies were similar in both. Since no dicentrics without fragments were obtained, it appeared that aberration frequencies in first-division cells only were being compared. (author)
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Human more complex than mouse at cellular level.
Directory of Open Access Journals (Sweden)
Alexander E Vinogradov
Full Text Available The family of transcription factors with the C2H2 zinc finger domain is expanding in the evolution of vertebrates, reaching its highest numbers in the mammals. The question arises: whether an increased amount of these transcription factors is related to embryogenesis, nervous system, pathology or more of them are expressed in individual cells? Among mammals, the primates have a more complex anatomical structure than the rodents (e.g., brain. In this work, I show that a greater number of C2H2-ZF genes are expressed in the human cells than in the mouse cells. The effect is especially pronounced for C2H2-ZF genes accompanied with the KRAB domain. The relative difference between the numbers of C2H2-ZF(-KRAB genes in the human and mouse cellular transcriptomes even exceeds their difference in the genomes (i.e. a greater subset of existing in the genome genes is expressed in the human cellular transcriptomes compared to the mouse transcriptomes. The evolutionary turnover of C2H2-ZF(-KRAB genes acts in the direction of the revealed phenomenon, i.e. gene duplication and loss enhances the difference in the relative number of C2H2-ZF(-KRAB genes between human and mouse cellular transcriptomes. A higher amount of these genes is expressed in the brain and embryonic cells (compared with other tissues, whereas a lower amount--in the cancer cells. It is specifically the C2H2-ZF transcription factors whose repertoire is poorer in the cancer and richer in the brain (other transcription factors taken together do not show this trend. These facts suggest that increase of anatomical complexity is accompanied by a more complex intracellular regulation involving these transcription factors. Malignization is associated with simplification of this regulation. These results agree with the known fact that human cells are more resistant to oncogenic transformation than mouse cells. The list of C2H2-ZF genes whose suppression might be involved in malignization is provided.
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International Nuclear Information System (INIS)
Wang Enxiu; Obeng-Adjei, Nyamekye; Ying Qihua; Meertens, Laurent; Dragic, Tanya; Davey, Robert A.; Ross, Susan R.
2008-01-01
Mouse mammary tumor virus (MMTV) is a pH-dependent virus that uses mouse transferrin receptor 1 (TfR1) for entry into cells. Previous studies demonstrated that MMTV could induce pH 5-dependent fusion-from-with of mouse cells. Here we show that the MMTV envelope-mediated cell-cell fusion requires both the entry receptor and low pH (pH 5). Although expression of the MMTV envelope and TfR1 was sufficient to mediate low pH-dependent syncytia formation, virus infection required trafficking to a low pH compartment; infection was independent of cathepsin-mediated proteolysis. Human TfR1 did not support virus infection, although envelope-mediated syncytia formation occurred with human cells after pH 5 treatment and this fusion depended on TfR1 expression. However, although the MMTV envelope bound human TfR1, virus was only internalized and trafficked to a low pH compartment in cells expressing mouse TfR1. Thus, while human TfR1 supported cell-cell fusion, because it was not internalized when bound to MMTV, it did not function as an entry receptor. Our data suggest that MMTV uses TfR1 for all steps of entry: cell attachment, induction of the conformational changes in Env required for membrane fusion and internalization to an appropriate acidic compartment
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High-resolution photoacoustic tomography of resting-state functional connectivity in the mouse brain
Nasiriavanaki, Mohammadreza; Xia, Jun; Wan, Hanlin; Bauer, Adam Quentin; Culver, Joseph P.; Wang, Lihong V.
2014-01-01
The increasing use of mouse models for human brain disease studies presents an emerging need for a new functional imaging modality. Using optical excitation and acoustic detection, we developed a functional connectivity photoacoustic tomography system, which allows noninvasive imaging of resting-state functional connectivity in the mouse brain, with a large field of view and a high spatial resolution. Bilateral correlations were observed in eight functional regions, including the olfactory bulb, limbic, parietal, somatosensory, retrosplenial, visual, motor, and temporal regions, as well as in several subregions. The borders and locations of these regions agreed well with the Paxinos mouse brain atlas. By subjecting the mouse to alternating hyperoxic and hypoxic conditions, strong and weak functional connectivities were observed, respectively. In addition to connectivity images, vascular images were simultaneously acquired. These studies show that functional connectivity photoacoustic tomography is a promising, noninvasive technique for functional imaging of the mouse brain. PMID:24367107
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Abe, Shinji; Kaneko, Mika Kato; Tsuchihashi, Yuki; Izumi, Toshihiro; Ogasawara, Satoshi; Okada, Naoto; Sato, Chiemi; Tobiume, Makoto; Otsuka, Kenji; Miyamoto, Licht; Tsuchiya, Koichiro; Kawazoe, Kazuyoshi; Kato, Yukinari; Nishioka, Yasuhiko
2016-09-01
Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti-human podoplanin mAb, NZ-1, and a rat-human chimeric anti-human podoplanin antibody, NZ-8, derived from NZ-1, which induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against podoplanin-positive MPM cell lines. In this study, we showed the antitumor effect of NZ-1, NZ-8, and NZ-12, a novel rat-human chimeric anti-human podoplanin antibody derived from NZ-1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ-1 and rat NK (CD161a(+) ) cells inhibited the growth of tumors and the production of pleural effusion in NCI-H290/PDPN or NCI-H226 orthotopic xenograft mouse models. NZ-8 and human natural killer (NK) (CD56(+) ) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ-12 induced potent ADCC mediated by human MNC, compared with either NZ-1 or NZ-8. Antitumor effects were observed following treatment with NZ-12 and human NK (CD56(+) ) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ-12 mediated by human NK (CD56(+) ) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin-targeting immunotherapy using both NZ-12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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Directory of Open Access Journals (Sweden)
Federico Castillo Blanco
2012-12-01
Full Text Available El treball que es presenta és un estudi de les competències autonòmiques en matèria d'ocupació pública i, molt especialment, d'allò que es refereix a les competències assumides per Catalunya en virtut de les reformes estatutàries esdevingudes en els últims anys i la incidència de la jurisprudència constitucional sobre aquestes reformes esdevinguda com a conseqüència de l'examen de la constitucionalitat del nou Estatut d'autonomia.El trabajo que se presenta es un estudio de las competencias autonómicas en materia de empleo público y, muy especialmente, en aquello que se refiere a las competencias asumidas por Cataluña en virtud de las reformas estatutarias acontecidas en los últimos años y la incidencia en las mismas de la jurisprudencia constitucional emitida como consecuencia del examen de la constitucionalidad del nuevo Estatuto de autonomía.This paper studies the powers of the governments of the autonomous regions with respect to public employment, in particular, 1 the powers taken on by Catalonia as a result of the statutory reforms of recent years, and 2 the impact on these powers of the constitutional case law that has developed as a result of the challenges to the constitutionality of the new Statute of Autonomy.
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Characterization of Bovine 5′-flanking Region during Differentiation of Mouse Embryonic Stem Cells
Directory of Open Access Journals (Sweden)
Hye-Jeong Jang
2015-12-01
Full Text Available Embryonic stem cells (ESCs have been used as a powerful tool for research including gene manipulated animal models and the study of developmental gene regulation. Among the critical regulatory factors that maintain the pluripotency and self-renewal of undifferentiated ESCs, NANOG plays a very important role. Nevertheless, because pluripotency maintaining factors and specific markers for livestock ESCs have not yet been probed, few studies of the NANOG gene from domestic animals including bovine have been reported. Therefore, we chose mouse ESCs in order to understand and compare NANOG expression between bovine, human, and mouse during ESCs differentiation. We cloned a 600 bp (−420/+181 bovine NANOG 5′-flanking region, and tagged it with humanized recombinant green fluorescent protein (hrGFP as a tracing reporter. Very high GFP expression for bovine NANOG promoter was observed in the mouse ESC line. GFP expression was monitored upon ESC differentiation and was gradually reduced along with differentiation toward neurons and adipocyte cells. Activity of bovine NANOG (−420/+181 promoter was compared with already known mouse and human NANOG promoters in mouse ESC and they were likely to show a similar pattern of regulation. In conclusion, bovine NANOG 5-flanking region functions in mouse ES cells and has characteristics similar to those of mouse and human. These results suggest that bovine gene function studied in mouse ES cells should be evaluated and extrapolated for application to characterization of bovine ES cells.
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Ichise, Hirotake; Hori, Akiko; Shiozawa, Seiji; Kondo, Saki; Kanegae, Yumi; Saito, Izumu; Ichise, Taeko; Yoshida, Nobuaki
2016-07-29
Temporal genetic modification of mice using the ligand-inducible Cre/loxP system is an important technique that allows the bypass of embryonic lethal phenotypes and access to adult phenotypes. In this study, we generated a tamoxifen-inducible Cre-driver mouse strain for the purpose of widespread and temporal Cre recombination. The new line, named CM32, expresses the GFPneo-fusion gene in a wide variety of tissues before FLP recombination and tamoxifen-inducible Cre after FLP recombination. Using FLP-recombined CM32 mice (CM32Δ mice) and Cre reporter mouse lines, we evaluated the efficiency of Cre recombination with and without tamoxifen administration to adult mice, and found tamoxifen-dependent induction of Cre recombination in a variety of adult tissues. In addition, we demonstrated that conditional activation of an oncogene could be achieved in adults using CM32Δ mice. CM32Δ;T26 mice, which harbored a Cre recombination-driven, SV40 large T antigen-expressing transgene, were viable and fertile. No overt phenotype was found in the mice up to 3 months after birth. Although they displayed pineoblastomas (pinealoblastomas) and/or thymic enlargement due to background Cre recombination by 6 months after birth, they developed epidermal hyperplasia when administered tamoxifen. Collectively, our results suggest that the CM32Δ transgenic mouse line can be applied to the assessment of adult phenotypes in mice with loxP-flanked transgenes.
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Energy Technology Data Exchange (ETDEWEB)
Padmanabhan, Balasundaram; Scharlock, Maria [RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan); Tong, Kit I. [Graduate School of Comprehensive Human Sciences, Center for Tsukuba Advanced Research Alliance and ERATO Environmental Research Project, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577 (Japan); Nakamura, Yoshihiro [RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan); Kang, Moon-Il; Kobayashi, Akira [Graduate School of Comprehensive Human Sciences, Center for Tsukuba Advanced Research Alliance and ERATO Environmental Research Project, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577 (Japan); Matsumoto, Takehisa; Tanaka, Akiko [RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan); Yamamoto, Masayuki [Graduate School of Comprehensive Human Sciences, Center for Tsukuba Advanced Research Alliance and ERATO Environmental Research Project, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577 (Japan); Yokoyama, Shigeyuki, E-mail: yokoyama@biochem.s.u-tokyo.ac.jp [RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan); Cellular Signaling Laboratory and Structurome Research Group, RIKEN Harima Institute at SPring-8, 1-1-1 Kouto, Mikazuki-cho, Sayo, Hyogo 679-5148 (Japan); Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan)
2005-01-01
Keap1-DC (Kelch/double-glycine repeat and C-terminal region) of mouse Keap1 has been overexpressed in E. coli, purified and crystallized using the vapour-diffusion method. Keap1 (Kelch-like ECH-associating protein 1) is a negative regulator of the Nrf2 transcription factor in the cytoplasm. The Kelch/DGR (double-glycine repeat) domain of Keap1 associates with Nrf2 as well as with actin filaments. A recombinant protein containing both the Kelch/DGR domain and the C-terminal region of mouse Keap1 was expressed in Escherichia coli, purified to near-homogeneity and crystallized by the sitting-drop vapour-diffusion method. The crystal belongs to space group P6{sub 1} or P6{sub 5}, with unit-cell parameters a = b = 102.95, c = 55.21 Å, and contains one molecule in the asymmetric unit. A complete diffraction data was collected to 2.25 Å resolution using an R-AXIS IV{sup ++} imaging plate mounted on an RA-Micro7 Cu Kα rotating-anode X-ray generator.
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Volland, Stefanie; Esteve-Rudd, Julian; Hoo, Juyea; Yee, Claudine; Williams, David S
2015-01-01
Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch's membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.
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Neuroinformatics of the Allen Mouse Brain Connectivity Atlas.
Kuan, Leonard; Li, Yang; Lau, Chris; Feng, David; Bernard, Amy; Sunkin, Susan M; Zeng, Hongkui; Dang, Chinh; Hawrylycz, Michael; Ng, Lydia
2015-02-01
The Allen Mouse Brain Connectivity Atlas is a mesoscale whole brain axonal projection atlas of the C57Bl/6J mouse brain. Anatomical trajectories throughout the brain were mapped into a common 3D space using a standardized platform to generate a comprehensive and quantitative database of inter-areal and cell-type-specific projections. This connectivity atlas has several desirable features, including brain-wide coverage, validated and versatile experimental techniques, a single standardized data format, a quantifiable and integrated neuroinformatics resource, and an open-access public online database (http://connectivity.brain-map.org/). Meaningful informatics data quantification and comparison is key to effective use and interpretation of connectome data. This relies on successful definition of a high fidelity atlas template and framework, mapping precision of raw data sets into the 3D reference framework, accurate signal detection and quantitative connection strength algorithms, and effective presentation in an integrated online application. Here we describe key informatics pipeline steps in the creation of the Allen Mouse Brain Connectivity Atlas and include basic application use cases. Copyright © 2014 Elsevier Inc. All rights reserved.
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The STR/ort mouse model of spontaneous osteoarthritis - an update.
Staines, K A; Poulet, B; Wentworth, D N; Pitsillides, A A
2017-06-01
Osteoarthritis is a degenerative joint disease and a world-wide healthcare burden. Characterized by cartilage degradation, subchondral bone thickening and osteophyte formation, osteoarthritis inflicts much pain and suffering, for which there are currently no disease-modifying treatments available. Mouse models of osteoarthritis are proving critical in advancing our understanding of the underpinning molecular mechanisms. The STR/ort mouse is a well-recognized model which develops a natural form of osteoarthritis very similar to the human disease. In this Review we discuss the use of the STR/ort mouse in understanding this multifactorial disease with an emphasis on recent advances in its genetics and its bone, endochondral and immune phenotypes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Mandelalides A-D, cytotoxic macrolides from a new Lissoclinum species of South African tunicate.
Sikorska, Justyna; Hau, Andrew M; Anklin, Clemens; Parker-Nance, Shirley; Davies-Coleman, Michael T; Ishmael, Jane E; McPhail, Kerry L
2012-07-20
Mandelalides A-D are variously glycosylated, unusual polyketide macrolides isolated from a new species of Lissoclinum ascidian collected from South Africa, Algoa Bay near Port Elizabeth and the surrounding Nelson Mandela Metropole. Their planar structures were elucidated on submilligram samples by comprehensive analysis of 1D and 2D NMR data, supported by mass spectrometry. The assignment of relative configuration was accomplished by consideration of homonuclear and heteronuclear coupling constants in tandem with ROESY data. The absolute configuration was assigned for mandelalide A after chiral GC-MS analysis of the hydrolyzed monosaccharide (2-O-methyl-α-L-rhamnose) and consideration of ROESY correlations between the monosaccharide and aglycone in the intact natural product. The resultant absolute configuration of the mandelalide A macrolide was extrapolated to propose the absolute configurations of mandelalides B-D. Remarkably, mandelalide B contained the C-4' epimeric 2-O-methyl-6-dehydro-α-L-talose. Mandelalides A and B showed potent cytotoxicity to human NCI-H460 lung cancer cells (IC(50), 12 and 44 nM, respectively) and mouse Neuro-2A neuroblastoma cells (IC(50), 29 and 84 nM, respectively).
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Probing the tumor microenvironment: collection and induction
Williams, James K.; Padgen, Michael R.; Wang, Yarong; Entenberg, David; Gertler, Frank; Condeelis, John S.; Castracane, James
2012-03-01
The Nano Intravital Device, or NANIVID, is under development as an optically transparent, implantable tool to study the tumor microenvironment. Two etched glass substrates are sealed using a thin polymer membrane to create a reservoir with a single outlet. This reservoir is loaded with a hydrogel blend that contains growth factors or other chemicals to be delivered to the tumor microenvironment. When the device is implanted in the tumor, the hydrogel will swell and release these entrapped molecules, forming a gradient. Validation of the device has been performed in vitro using epidermal growth factor (EGF) and MenaINV, a highly invasive, rat mammary adenocarcinoma cell line. In both 2-D and 3-D environments, cells migrated toward the gradient of EGF released from the device. The chorioallantoic membrane (CAM) of White Leghorn chicken eggs is being utilized to grow xenograft tumors that will be used for ex vivo cell collection. Device optimization is being performed for in vivo use as a tool to collect the invasive cell population. Preliminary cell collection experiments in vivo were performed using a mouse model of breast cancer. As a second application, the device is being explored as a delivery vehicle for chemicals that induce controlled changes in the tumor microenvironment. H2O2 was loaded in the device and generated intracellular reactive oxygen species (ROS) in cells near the device outlet. In the future, other induction targets will be explored, including hypoglycemia and the manipulation of extracellular matrix stiffness.
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A cytotoxic serine proteinase isolated from mouse submandibular gland.
Shimamura, T; Nagumo, N; Ikigai, H; Murakami, K; Okubo, S; Toda, M; Ohnishi, R; Tomita, M
1989-08-01
We have isolated a novel cytotoxic factor from the submandibular glands of male BALB/c mice by Sephadex G-50 gel filtration chromatography and reverse-phase HPLC. The cytotoxic factor is a serine proteinase, which belongs to the mouse glandular kallikrein (mGK) family, with an Mr of approximately 27,000. The purified serine proteinase showed cytotoxic activity against mouse thymocytes in a dose-dependent manner, and a serine proteinase inhibitor, diisopropyl fluorophosphate, blocked its cytotoxic activity.
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A sensitive radioimmunoassay for a component of mouse casein
International Nuclear Information System (INIS)
Enami, Jumpei; Nandi, S.; California Univ. Berkeley
1977-01-01
Mouse casein (m.w. 22,000 daltons) has been purified by employing Sephadex G-100 and DEAE-cellulose column chromatographies. A sensitive radioimmunoassay method has been developed by using [ 125 I]-labelled casein and antiserum elicited in rabbits after injection of glutaraldehyde-treated casein. The assay method is capable of detecting as little as 0.1 ng of casein. The use of the present radioimmunoassay method in detecting casein production in cultured mouse mammary explants has also been demonstrated
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Lipopolysaccharide administration in the dominant mouse destabilizes social hierarchy.
Cohn, Daniel Wagner Hamada; Gabanyi, Ilana; Kinoshita, Denise; de Sá-Rocha, Luiz Carlos
2012-09-01
Sickness behavior is a set of behavioral changes that are part of an adaptive strategy to overcome infection. Mice that interact with conspecifics displaying sickness behavior also show relevant behavioral changes. In this work we sought to determine the role of sickness behavior display by a dominant mouse as a promoter of hierarchy instability. We treated the dominant mouse within a dyad with lipopolysaccharide (LPS) (400 μg/kg, i.p.) for three consecutive days and assessed social dominance behavior. Since elder animals display increased inflammatory responses and the behaviors toward conspecifics are influenced by kinship we also assessed whether kinship and age, might influence sickness related hierarchy instability. Our results show that administration of LPS in the dominant mouse promotes social instability within a dyad, and indicates that this instability could be influenced by kinship and age. Copyright © 2012 Elsevier B.V. All rights reserved.
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Production of peptide antisera specific for mouse and rat proinsulin C-peptide 2
DEFF Research Database (Denmark)
Blume, N; Madsen, O D; Kofod, Hans
1990-01-01
for antibody binding to the immunizing antigen. Antisera to C-peptide 2, stained islet beta-cells on mouse and rat, but not monkey pancreas sections in immunocytochemical analysis. Preabsorption to the synthetic C-peptide 2, but not the synthetic mouse and rat C-peptide 1 abolished staining. In conclusion we......Mice and rats have two functional non-allelic insulin genes. By using a synthetic peptide representing a common sequence in mouse and rat C-peptide 2 as antigen, we have produced rabbit antisera specific for an epitope which is not present in mouse or rat C-peptide 1. Long-term immunization did...... not seem to increase the end point titre as tested in direct ELISA. The specificity of the antiserum was determined by competitive ELISA and histochemistry on pancreas sections. Only the synthetic C-peptide 2, but not the homologous synthetic C-peptide 1 from mouse and rat competed efficiently in ELISA...
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Lascols, O; Cherqui, G; Munier, A; Picard, J; Capeau, J
1994-05-01
To investigate whether glycanic chains of prolactin receptors (PRL-R) play a role in hormone binding activity, comparison was made of rat and mouse liver solubilized receptors with respect to both their affinity for the hormone and their glycosylation properties. As compared with rat receptors, mouse receptors exhibited a 2-fold higher affinity for human growth hormone (hGH), the hormone being bound by both tissues with a lactogenic specificity. Along with this increased affinity, mouse receptors had a 2 lower M(r) relative to rat receptors (62 kDa versus 64 kDa as measured on hGH cross-linked receptors). These differences could be ascribed to different glycosylation properties of the receptors from the two species, as supported by the followings. 1) After treatment with endoglycosidase F (endo F), rat and mouse PRL-R no longer exhibited any difference in their M(r) (54 kDa for both cross-linked receptors). 2) Neuraminidase treatment increased by 37% the binding of hGH to mouse receptors, but was ineffective on the hormone-binding to rat receptors. Conversely, wheat germ agglutinin (WGA), another sialic acid specific probe, decreased hGH binding to rat receptors by 25%, but had no effect on this process for mouse ones. 3) Marked differences were observed in the recoveries of rat and mouse hormone-receptor (HR) complexes from ricin-1- (RCA1-), concanavalin A- (ConA-) and WGA-immobilized lectins. These differences were reduced (RCA1 and ConA) or abolished (WGA) after rat and mouse receptor desialylation by neuraminidase, a treatment which decreased the M(r) of both receptors by 2 kDa. Taken together, these results strongly suggest that the PRL-R from rat and mouse liver contain biantennary N-linked oligosaccharidic chains with distinct type of sialylation, which may account for their differential hormone-binding affinities.
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Give a Book, Take a Book | Poster
Collection has begun for the 15th Annual Book & Media Swap sponsored by the Scientific Library. NCI at Frederick staff can use this opportunity to clear out personal book and DVD shelves of unwanted materials, donate them to the swap, and then receive “new” materials in return. The library staff will collect materials through Tuesday, Oct. 27. Kick-off day for the event is
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Age-related changes of MAO-A and -B distribution in human and mouse brain.
Mahy, N; Andrés, N; Andrade, C; Saura, J
2000-01-01
Age-related changes of MAO-A and -B were studied in human and BL/C57 mouse brain areas (substantia nigra, putamen and cerebellum). [3H]Ro41-1049 and [3H]lazabemide were used as selective radioligands to image and quantify MAO-A and MAO-B respectively by enzyme autoradiography. MAO-A binding was higher in mouse, whereas MAO-B binding was higher in human. With aging, mouse MAO-A was significantly reduced between 4 and 8 weeks and remained unchanged until 19 months followed by a slight increase between 19 and 25 months. In contrast, no clear variation was observed in humans between the age of 17-93 years. In most of the structures studied a clear age-related increase in MAO-B was observed beginning in mouse brain at 4 weeks, whereas in human tissue this increase started at the age of 50-60 years. These results show marked differences in the levels and variations of mouse and human MAO-A and -B associated with aging and should be taken into account when extrapolating experimental data from mouse to human.
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Variation in the timing of reproduction of the four-striped field mouse ...
African Journals Online (AJOL)
Variation in the timing of reproduction of the four-striped field mouse, Rhabdomys pumilio , in ... Open Access DOWNLOAD FULL TEXT ... We used the four-striped field mouse, Rhabdomys pumilio (Sparrmann, 1784), to test the hypothesis that ...
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Histologic scoring of gastritis and gastric cancer in mouse models.
Rogers, Arlin B
2012-01-01
Histopathology is a defining endpoint in mouse models of experimental gastritis and gastric adenocarcinoma. Presented here is an overview of the histology of gastritis and gastric cancer in mice experimentally infected with Helicobacter pylori or H. felis. A modular histopathologic scoring scheme is provided that incorporates relevant disease-associated changes. Whereas the guide uses Helicobacter infection as the prototype challenge, features may be applied to chemical and genetically engineered mouse models of stomach cancer as well. Specific criteria included in the combined gastric histologic activity index (HAI) include inflammation, epithelial defects, oxyntic atrophy, hyperplasia, pseudopyloric metaplasia, and dysplasia or neoplasia. Representative photomicrographs accompany descriptions for each lesion grade. Differentiation of genuine tumor invasion from pseudoinvasion is highlighted. A brief comparison of normal rodent versus human stomach anatomy and physiology is accompanied by an introduction to mouse-specific lesions including mucous metaplasia and eosinophilic droplets (hyalinosis). In conjunction with qualified pathology support, this guide is intended to assist research scientists, postdoctoral fellows, graduate students, and medical professionals from affiliated disciplines in the interpretation and histologic grading of chronic gastritis and gastric carcinoma in mouse models.
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Automated whole-genome multiple alignment of rat, mouse, and human
Energy Technology Data Exchange (ETDEWEB)
Brudno, Michael; Poliakov, Alexander; Salamov, Asaf; Cooper, Gregory M.; Sidow, Arend; Rubin, Edward M.; Solovyev, Victor; Batzoglou, Serafim; Dubchak, Inna
2004-07-04
We have built a whole genome multiple alignment of the three currently available mammalian genomes using a fully automated pipeline which combines the local/global approach of the Berkeley Genome Pipeline and the LAGAN program. The strategy is based on progressive alignment, and consists of two main steps: (1) alignment of the mouse and rat genomes; and (2) alignment of human to either the mouse-rat alignments from step 1, or the remaining unaligned mouse and rat sequences. The resulting alignments demonstrate high sensitivity, with 87% of all human gene-coding areas aligned in both mouse and rat. The specificity is also high: <7% of the rat contigs are aligned to multiple places in human and 97% of all alignments with human sequence > 100kb agree with a three-way synteny map built independently using predicted exons in the three genomes. At the nucleotide level <1% of the rat nucleotides are mapped to multiple places in the human sequence in the alignment; and 96.5% of human nucleotides within all alignments agree with the synteny map. The alignments are publicly available online, with visualization through the novel Multi-VISTA browser that we also present.
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MRI to assess chemoprevention in transgenic adenocarcinoma of mouse prostate (TRAMP)
International Nuclear Information System (INIS)
Arbab, Ali S; Shankar, Adarsh; Varma, Nadimpalli RS; Deeb, Dorrah; Gao, Xiaohua; Iskander, ASM; Janic, Branislava; Ali, Meser M; Gautam, Subhash C
2011-01-01
The current method to determine the efficacy of chemoprevention in TRAMP mouse model of carcinoma of prostate (CaP) is by extracting and weighing the prostate at different time points or by immunohistochemistry analysis. Non-invasive determination of volumes of prostate glands and seminal vesicles before, during and after treatment would be valuable in investigating the efficacy of newer chemopreventive agents in CaP. The purpose of this study was to determine whether in vivo magnetic resonance imaging (MRI) using a 3 tesla clinical MRI system can be used to follow the effect of chemoprevention in TRAMP model of mouse CaP. Mice were randomized into control and treated groups. The animals in treated group received 10 µmol/kg of CDDO, 5 days a week for 20 weeks. Animals underwent in vivo MRI of prostate gland and seminal vesicles by a clinical 3 Tesla MRI system just before (at 5 weeks), during and at the end of treatment, at 25 weeks. T1-weighted and fat saturation (FATSAT) multiecho fast spin echo T2- weighted images (T2WI) were acquired. Volume of the prostate glands and seminal vesicles was determined from MR images. T2 signal intensity changes in the seminal vesicles were determined by subtracting higher echo time (TE) from lower TE T2WI. Following treatments all animals were sacrificed, prostate and seminal vesicles collected, and the tissues prepared for histological staining. All data were expressed as mean ± 1 standard deviation. Two-way or multivariate analysis of variance followed by post-hoc test was applied to determine the significant differences. A p-value of <0.05 was considered significant. Histological analysis indicated tumor in 100% of control mice, whereas 10% of the treated mice showed tumor in prostate gland. Both MRI and measured prostate weights showed higher volume/weight in control mouse group. MRI showed significantly higher volume of seminal vesicles in control animals and T2 signal intensity changes in seminal vesicles of control mice
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Bokil, Nilesh J.
2011-11-01
Uropathogenic E. coli (UPEC) are the primary cause of urinary tract infections. Recent studies have demonstrated that UPEC can invade and replicate within epithelial cells, suggesting that this bacterial pathogen may occupy an intracellular niche within the host. Given that many intracellular pathogens target macrophages, we assessed the interactions between UPEC and macrophages. Colonization of the mouse bladder by UPEC strain CFT073 resulted in increased expression of myeloid-restricted genes, consistent with the recruitment of inflammatory macrophages to the site of infection. In in vitro assays, CFT073 was able to survive within primary mouse bone marrow-derived macrophages (BMM) up to 24h post-infection. Three additional well-characterized clinical UPEC isolates associated with distinct UTI symptomatologies displayed variable long-term survival within BMM. UPEC strains UTI89 and VR50, originally isolated from patients with cystitis and asymptomatic bacteriuria respectively, showed elevated bacterial loads in BMM at 24h post-infection as compared to CFT073 and the asymptomatic bacteriuria strain 83972. These differences did not correlate with differential effects on macrophage survival or initial uptake of bacteria. E. coli UTI89 localized to a Lamp1 + vesicular compartment within BMM. In contrast to survival within mouse BMM, intracellular bacterial loads of VR50 were low in both human monocyte-derived macrophages (HMDM) and in human T24 bladder epithelial cells. Collectively, these data suggest that some UPEC isolates may subvert macrophage anti-microbial pathways, and that host species differences may impact on intracellular UPEC survival. © 2011 Elsevier GmbH.
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Directory of Open Access Journals (Sweden)
Jin Hong
2009-12-01
Full Text Available Abstract Background The dystrophin glycoprotein complex is disrupted in Duchenne muscular dystrophy and many other neuromuscular diseases. The principal heterodimeric partner of dystrophin at the heart of the dystrophin glycoprotein complex in the main clinically affected tissues (skeletal muscle, heart and brain is its distant relative, α-dystrobrevin. The α-dystrobrevin gene is subject to complex transcriptional and post-transcriptional regulation, generating a substantial range of isoforms by alternative promoter use, alternative polyadenylation and alternative splicing. The choice of isoform is understood, amongst other things, to determine the stoichiometry of syntrophins (and their ligands in the dystrophin glycoprotein complex. Results We show here that, contrary to the literature, most α-dystrobrevin genes, including that of humans, encode three distinct syntrophin-binding sites, rather than two, resulting in a greatly enhanced isoform repertoire. We compare in detail the quantitative tissue-specific expression pattern of human and mouse α-dystrobrevin isoforms, and show that two major gene features (the novel syntrophin-binding site-encoding exon and the internal promoter and first exon of brain-specific isoforms α-dystrobrevin-4 and -5 are present in most mammals but specifically ablated in mouse and rat. Conclusion Lineage-specific mutations in the murids mean that the mouse brain has fewer than half of the α-dystrobrevin isoforms found in the human brain. Our finding that there are likely to be fundamental functional differences between the α-dystrobrevins (and therefore the dystrophin glycoprotein complexes of mice and humans raises questions about the current use of the mouse as the principal model animal for studying Duchenne muscular dystrophy and other related disorders, especially the neurological aspects thereof.
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EPR detection of free radicals in UV-irradiated skin: mouse versus human
International Nuclear Information System (INIS)
Jurkiewicz, B.A.; Buettner, G.R.
1996-01-01
Ultraviolet radiation produces free radicals in Skh-1 mouse skin, contributing to photoaging and carcinogenesis. If a mouse model is a general indicator of free radical processes in human skin photobiology, then radical production observed in mouse and human skin should be directly comparative. In this work we show that UV radiation (λ > 300 nm, 14 μW/cm 2 UVB; 3.5 mW/cm 2 UVA) increases the ascorbate free radical (Asc) electron paramagnetic resonance (EPR) signal in both Skh-1 mouse skin (45%) and human facial skin biopsies (340%). Visible light (λ > 400 nm; 0.23 mW/cm 2 UVA) also increased the Ascsignal in human skin samples (45%) but did not increase baseline mouse Asc, indicating that human skin is more susceptible to free radical formation and that a chromophore for visible light may be present. Using EPR spin-trapping techniques, UV radiation produced spin adducts consistent with trapping lipid alkyl radicals in mouse skin (α-[4-pyridyl 1-oxide]-N-tert-butyl nitrone/alkyl radical adduct; a N = 15.56 G and a H 2.70 G) and lipid alkoxyl radicals in human skin (5,5-dimethylpyrroline -1-oxide/alkoxyl radical adduct; a N = 14.54 G and a H = 16.0 G). Topical application of the iron chelator Desferal to human skin significantly decreases these radicals (∼50%), indicating a role for iron in lipid peroxidation. (Author)
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Fine-scale maps of recombination rates and hotspots in the mouse genome.
Brunschwig, Hadassa; Levi, Liat; Ben-David, Eyal; Williams, Robert W; Yakir, Benjamin; Shifman, Sagiv
2012-07-01
Recombination events are not uniformly distributed and often cluster in narrow regions known as recombination hotspots. Several studies using different approaches have dramatically advanced our understanding of recombination hotspot regulation. Population genetic data have been used to map and quantify hotspots in the human genome. Genetic variation in recombination rates and hotspots usage have been explored in human pedigrees, mouse intercrosses, and by sperm typing. These studies pointed to the central role of the PRDM9 gene in hotspot modulation. In this study, we used single nucleotide polymorphisms (SNPs) from whole-genome resequencing and genotyping studies of mouse inbred strains to estimate recombination rates across the mouse genome and identified 47,068 historical hotspots--an average of over 2477 per chromosome. We show by simulation that inbred mouse strains can be used to identify positions of historical hotspots. Recombination hotspots were found to be enriched for the predicted binding sequences for different alleles of the PRDM9 protein. Recombination rates were on average lower near transcription start sites (TSS). Comparing the inferred historical recombination hotspots with the recent genome-wide mapping of double-strand breaks (DSBs) in mouse sperm revealed a significant overlap, especially toward the telomeres. Our results suggest that inbred strains can be used to characterize and study the dynamics of historical recombination hotspots. They also strengthen previous findings on mouse recombination hotspots, and specifically the impact of sequence variants in Prdm9.